Abstract

Simultaneous diagnosis and treatment during chemotherapy is an attractive topic in nano-oncology. Here, Capecitabine, as a well-known chemodrug, demonstrates notable fluorescence properties according to laser induced fluorescence (LIF) spectroscopy. Capecitabine is vastly used for breast and colon cancer therapy, while its excitation wavelength lies over UV region (180-350 nm). ArF laser with an excitation wavelength at 193 nm is exploited to stimulate the fluorophore molecules. As a biocompatible fluorophore, Capecitabine reveals predominant fluorescence characteristics for simultaneous diagnosis during chemotherapeutic treatment. The laser energy and repetition rate affect on the spectral properties of Capecitabine have been studied in this work to find out the optimal exposure condition. Moreover, the spectral shifts in terms of fluorophore concentrations are obtained for the purpose of fluorescence imaging. Here, lucid red shift in terms of chemodrug concentration and the red shift in various GO densities at certain Capecitabine concentrations are reported. Spectral red shift of Capecitabine directly addresses the concentration distribution and penetration depth of the chemodrug. As a consequence, LIF spectroscopy of Capecitabine is beneficial for fluorescence imaging and confocal mapping of cancerous tissues during simultaneous diagnosis/imaging and treatment. Similarly, LIF of RdB as a reference fluorophore is carried out to compare its fluorescence properties with those parameters in the chemodrugs of interest.

© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Corrections

17 July 2020: Typographical corrections were made to the author listing and author affiliations.

1. Introduction

Capecitabine (Xeloda) (N4-pentoxycarbonyl-5‘-deoxy-5-fluorocytidine) is a fluorescent active fluoropyrimidinecarbamate and announced to be the best oral chemodrug for adjuvant treatment of many cancers such as colon, breast, gastrointestinal, pancreatic, ovarian and peritoneal [1,2]. Fluorouracil (5-FU) the end product of Capeciatbine, preferentially formed/accumulated in tumors is also fluorescent upon excitation with UV. 5-FU bolus needs to be used along with leucovorin (LV) injection to enhance the cellular permeability and therapeutic effects of FU to the great extent [3,4]. Whereas Capecitabine is administrated as an oral form of FU + LV combination with the superior efficacy and improved safety profile [5]. This prodrug which is selectively activated by tumor cells and its cytotoxic moiety can be easily dissolved in deionized water. Recently, the optical spectroscopic techniques are used as in vivo/ex vivo identification and diagnosis of cancerous tissues to exhibit a number of advantages against traditional biopsy [68]. Laser induced fluorescence (LIF) and Laser induced Breakdown Spectroscopy (LIBS) are taken account as the online alternatives against the offline confocal imaging technique during oncology surveys [911]. Moreover, LIBS and LIF techniques are employed as diagnostic tools to discriminate the cancerous tissues from normal membranes [1214]. Dissimilar to other competing techniques, the imaging based on auto fluorescence spectroscopy can be implemented using endogenous fluorophores. On the other hand, the substantial privileges of the innate fluorescence characteristics of some chemodrugs do contribute as biocompatible fluorophores during the simultaneous diagnosis and chemotherapy. Recently, the fluorescence parameters of different chemodrugs such as, Navelbine, Paclitaxel, Bleomycin, Doxorubicin, Irinotecan and Gemcitabine are investigated in various concentrations comparing their fluorescence properties with reference dye-Rhodamine 6G (Rd6G) [15,16]. This emphasizes the potential of optically activated chemodrugs in future cancer diagnosis/therapy.

The quantitative measurements of Capecitabine using HPLC-UV measurements of human plasma was previously reported [17]. Also anti-metastatic effect of Capecitabine on colon cancer have been studied using the imaging of DNAs labeled with green fluorescent protein (GFP) using the fluorescence confocal laser microscopy [18]. The LIF spectroscopy can be carried out to assess the Capecitabine behavior in intercellular environments. In this article absorption spectra are obtained in three different Capecitabine concentrations using the UV/VIS spectroscopy to find the behavior of absorption spectra of Capecitabine. Therefore, spectral absorbance region of Capecitabine reveals that ArF excitation laser line is suitable in LIF measurements. Furthermore, LIF spectroscopy of dissolved Capecitabine in deionized water is extensively investigated over the wide concentration range (0.25-10 mg/ml) to characterize the optical fluorescence properties of the chemodrug of interest. Regarding the normal protocols for oral administration of Capecitabine, the appropriate dose for treatment is below 0.25 mg/ml [19]. However, in order to characterize the maximum fluorescence intensity including concentration of maximum peak Cp, quantum yield, self-quenching, etc. using LIF Intensity-Concentration curve, higher concentrations are examined here suitable for imaging and diagnosis. Spectral shift variations of Capecitabine versus concentration attest its fingerprint characteristics during imaging/chemotherapy. Moreover, the modified Beer-Lambert equation is verified according to data collection of fluorescence signals in various concentrations. As a result, the quantum yield of Capecitabine against other chemodrugs is determined. Also, the effects of laser energy and repetition rate on the signal intensity are examined to find out the optimal experimental conditions during LIF spectroscopy.

Eventually, the fluorescence properties of (nanoparticle + chemodrug) suspensions are worthwhile in nano-medicine regarding the drug delivery concept. Graphene oxide (GO) and nano diamond (ND) as biocompatible nanostructures show efficient properties for drug delivery applications. Recently, LIF spectroscopy of different nanoparticles in Rd6G and RdB fluorophores has been characterized [20,21]. Furthermore, the quenching effects of GO and ND nanoparticles are studied on the fluorescence properties of DOX chemodrug. Dynamic drug delivery is realized by nanoparticle labeling of chemodrug under laser activation to track selective drug release [7]. Here, fluorescence characteristics of (Capecitabine + GO) suspensions in terms of GO densities are investigated at a certain Capecitabine concentration. As a result, the quenching effect of GO on the fluorescence emission of Capecitabine is measured using Stern-Volmer formalism. Also the spectral shift effects of GO nanoparticle on LIF spectra are reported as the characteristic fingerprint at various densities. Eventually, the fluorescent characteristics of RdB fluorophore as reference along with the (RdB + GO) quenching performance are carried out to verify the Capecitabine strength in fluorescence spectroscopy.

This approach deals with efficient method of drug delivery during cancer therapy. The absorbance and fluorescence properties of Capecitabine are investigated here to collect necessary data for biomedical engineers and clinicians who would like to study the Capecitabine chemodrug in simultaneous imaging/diagnosis/treatment of tumors in practice. To the best of our knowledge, no similar report has been found so far in the literature to investigate the fluorescence properties of Capecitabine chemodrug. Particularly, the results of the present work can be exploited for LIF imaging and cancer treatment in the course of (CAP + GO) delivering to unhealthy tissue target. Both hyper thermal effects of GO and Capecitabine chemotherapy act synergetic to enhance the efficiency of treatment.

2. Materials and methods

2.1. Materials

Capecitabine with MW=359.354 g/mol is provided by (Roche GmbH) in 500mg tablets and RdB (C28H31CIN2O3) dye is supplied by Across Organics with MW = 479.02 g/mol. The optical fluorescence properties of Capecitabine in deionized water solvent is studied over wide concentration range (0.25-10 mg/ml). Graphene oxide (C20O154) sheets are provided by Sigma-Aldrich Co. with monolayers 0.7-1.4 nm thickness and lateral size of 5-100 µm dispersed in deionized water by 1 mg/ml density.

Successively, LIF spectra of (CAP + GO) and (RdB + GO) are investigated. The suspensions are prepared in the form of various GO densities (2.5-250 µg/ml) as additives to Capecitabine and RdB solutions.

2.2. Methods

In high fluorophore concentrations with absorbance values > 0.05, reabsorption events called inner filter effect causes the deviation in linear dependence of fluorescence signal with concentration. Different mathematical models are used to correct this effect and derive the actual fluorescence intensity [22]. According to the modified Beer-Lambert equation as one of the straightforward models, the fluorescence intensity If is associated with proportionality factor β, self-quenching parameter k, as well as the absorbed energy which depends on the concentration of fluorophore C, cuvette length of biomaterial l and extinction coefficient α as given below [15,16,23,24]:

$${I_f} = \beta (1 - {10^{ - \alpha Cl}}){e^{ - kCl}}$$

Fluorescence emission is expected to be quenched by the scattering processes based on the re-absorption phenomenon and concentration of the non-excited fluorophores [25]. A right angle experimental configuration of detection is implemented here and fluorescence emission is supposed to be isotropic. Note that Eq. (1) fits If versus C not only for Capecitabine but also in favour of other chemodrugs of interest such as doxorubicin, paclitaxel, bleomycin, irinotecan, gemcitabine and navelbine according to H. Motlagh et al. [15,16]. Besides, Eq. (1) as the position independent relation is unable to predict the photon trajectory. In this case, Monte Carlo simulation can elaborate the photon trajectory in hybrid media.

On the other hand, the fluorescence intensity If is proportional to the quantum yield ηf, absorbed emission Ia and the ratio of averaged wavelength of fluorescence signal $\overline {{\lambda _f}}$ to the wavelength of absorption peak ${\lambda _{abs}}$. Regarding the Stokes shift, Δ= ($\lambda _f^{}$-$\lambda _{abs}^{}$) the spectral difference between the fluorescence and absorption peak wavelengths, fluorescence signal intensity can be rewritten as below [13,15,16]:

$${I_f} = {I_a}{\eta _f}\frac{{\overline {{\lambda _f}} }}{{\lambda _{abs}^{}}} = {I_a}{\eta _f}\frac{{\overline {{\lambda _f}} }}{{\Delta + \lambda _f^{}}}$$
where the fluorescence intensity decreases at larger stokes shift Δ. Excitation wavelength λexc is not necessarily the same as λabs, while it is much better to be close to the absorption peak wavelength. Besides, Stern-Volmer (S.V) equation describes the intrinsic fluorescence intensity without (F0) and with nano quencher (F):
$${{\boldsymbol F}_0}/{\boldsymbol F} = 1 + {\boldsymbol K}[{\boldsymbol Q}]$$
K and Q ascertain quenching coefficient and quencher density respectively [7,21].

2.3. Instrumentations

UV-VIS absorption spectra of Capecitabine are measured by the Cary 60 spectro-photometer of 1.5 nm optical resolution over 190-1100 nm spectral range. ArF excimer laser with pulsed energy of 130-260 mJ/pulse, 15 ns duration and the repetition rate of 1-10 Hz is employed as the UV excitation source during our systematic LIF measurements. Fluorescence emissions are collected through the modular spectrometer AvaSpec Starline (Avantes) over the optical range of 200-1100 nm with spectral resolution of 0.5 nm. The AvaSpec-2048 with 2048 pixel CCD detector equipped with order sorting longpass filters (OSC-UA) of Avantes Company to eliminate the nonlinear higher order effects as well as detector collection lens to enhance the detection sensitivity. Second-order effects can be filtered out, using two permanently installed long-pass optical filters (350 nm and 600 nm) in an order-sorting coating on a window in front of the detector.

The LIF spectra are obtained by optical triggering using AvaTrigger with the 10 ms integration time and taking the average over 50 repetitive spectra. Figure 1(a) depicts the LIF experimental arrangement in right angle configuration avoiding the laser pulse to enter the spectrometer. Mean refractive index of RdB and Capecitabine are measured using refractometer via Abbe technique. Finally, the ArF UV laser is exploited with 160 mJ/pulse energy and 1 Hz PRR to activate the (Cap + GO) solution. The second harmonic generation (SHG), continuous wave (CW) Nd:YAG laser made by Chinese CNI company with 100 mW average power and 0.7 mm beam diameter at λ=532 nm is employed as excitation laser for RdB fluorophore as well as (RdB + GO) solution.

 figure: Fig. 1.

Fig. 1. (a) Experimental set-up for LIF measurement of Capecitabine, including coherent excitation source of ArF laser, detector with triggered modular spectrometer and the optical collimating lens (b) UV-VIS absorption spectra of Capecitabine in different concentration characterizing three absorbance peaks at 216, 237 and 302 nm. Inset: absorption peak intensity versus fluorophore concentrations (c) Normalized overlapping area between absorption and LIF spectra as well as absorbance peak at 216 nm, emission peak at 408 nm and stokes shift Δ=202 nm. Note: Cuvette length is 1 cm.

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3. Results and discussions

3.1. LIF spectroscopy of Capecitabine

Figure 1(b) depicts the UV-VIS absorption spectra for different concentrations of Capecitabine. UV-VIS spectroscopy of Capecitabine attests high absorbance over UV region having several at peaks at 216, 237 and 302 nm. Here, ArF laser at 193 nm is selected to be coupled with the broad absorption band of Capecitabine UV. Figure 1(b) inset illustrates the spectral absorbance in terms of various chemodrug concentrations indicating a linearity of absorption peak versus concentration. In fact, the absorbance demonstrates linear relation with concentration at dilute molar concentrations less than 0.06 mg/ml due to Beer-Lambert equation. Figure 1(c) depicts the typical overlap between absorption and emission spectra emphasizing the spectral red shift due to the reabsorptions events.

Figure 2(a) shows LIF signals versus Capecitabine concentrations ranging 0.25-10 mg/ml characterizing the maximum intensity at peak wavelength of 408 nm at characteristic Cp=2.5 mg/ml. The latter is Capecitabine concentration with maximum fluorescence signal. By increasing the concentration above 2.5 mg/ml the signal falls down due to the static/dynamic quenching events. The same fluorescence properties are revealed during the implemented photoluminescence measurements. The behavior is certainly similar to the LIF properties of other fluorescent chemodrugs such as Irinotecan, Navelbine, Paclitaxel, Bleomycin, Gemcitabine and Doxorubicin [15,16]. The positive slope of the plot appears at low concentrations arises from the elevated population of excited levels of corresponding transitions. At dense concentrations, the aggregation of the molecules leads to self-quenching and Förster resonance energy transfer (FRET) [26]. The inset of Fig. 2(a) reveals the spectra at various concentrations showing 408 nm central peak. The signal amplitude and emission wavelength lucidly vary in terms of Capecitabine concentration. The quenching events consists of static processes such as FRET and self-quenching effects, as well as dynamic processes i.e, collisional recombination interactions.

 figure: Fig. 2.

Fig. 2. (a) LIF peak intensity versus Capecitabine concentration ranging 0.25-10 (mg/ml). Inset: Corresponding LIF spectra of different concentrations b) Emission wavelength in terms of Capecitabine concentration indicating a lucid red shift of 6 nm. This is mainly due to the reabsorption events that arises from the spectral overlap of absorbance and fluorescence emission. Inset: FWHM of LIF signals versus concentration. Note that FWHM reduction arises from the shrinkage of overlapping area that strongly affects the fluorescence properties of Capecitabine to slow down the rate of red shift at dense concentrations. Number of 50 trial measurements are averaged to find each datapoint.

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Figure 2(b) plots the emission peak wavelength in terms of Capecitabine concentration and the inset displays the corresponding FWHM versus Capecitabine concentration. There is notable overlapping area between spectral absorbance-emission according to Fig. 1(c) to enhance the reabsorption events leading to maximum red shifts of 6nm. Furthermore, the rate of red shift slows down at larger concentrations mainly due to successive FRET and aggregation events leading to the obliteration of fluorophores. Similarly, the FWHM of LIF peak falls down at higher concentrations according to Fig. 2(b) inset.

3.2. Effect of laser properties on Capecitabine fluorescence

To find the optimum experimental conditions for detection of fluorescence signals, the spectra of Capecitabine are measured by changing the pulse energy of ArF laser. The shots’ energy vary from 130 mJ to 260 mJ to study the corresponding effect on LIF spectra. Figure 3(a) displays the signal intensity versus the pulse energy at 1 Hz repetition rate for a typical Capecitabine concentration of 2.5 mg/ml. Figure 3(a) inset (i) represents LIF spectra of Capecitabine at different pulse energies. Naturally, the fluorescence signal increases as a function of pulse energy due to the elevated population of excited molecules within the active area. The highest fluorescence emission appears at 230 mJ/Pulse. However, by increasing the laser energy greater than 230 mJ/Pulse, the fluorescence signal reduces mostly because of the saturation of excited molecules to hinder further promotion of the excited states.

 figure: Fig. 3.

Fig. 3. (a) Capecitabine fluorescence signal intensity versus pulse energy of ArF laser, inset (i) LIF spectra at different pulse energies ranging 130-270 mJ, inset (ii) Emission wavelength versus pulse energy (b) LIF peak intensity in terms of PRR of ArF laser. Inset (i) Capecitabine LIF spectra versus PRR (1-10 Hz) inset (ii) output pulsed energy in different PRRs. Number of 50 trial measurements are averaged to find each datapoint.

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Then, no need for extra energy to activate excessive species, however the static/dynamic collisional quenching events induce the fluorescence signal to level down. Assuming the completely homogenous ArF laser pulse, then the linear behavior of fluorescence signal with pulse energy is expected [27]. However, the collapse of fluorescence intensity takes place at more intense UV shots energy above 230 mJ/Pulse regarding the nature of molecular saturation of excitation. Moreover, the pulse energy does not affect the central peak emission [28], therefore no spectral shift is recorded. Figure 3(a) inset (ii) depicts emission wavelength at 408 nm versus pulse energy that is invariant at 408 nm as expected.

Figure 3(b) illustrates the signal intensity in terms of pulse repetition rate (P.R.R) for a typical Capecitabine concentration of Cp=2.5 mg/ml. The fluorescent emission has been examined in three pulse repetition rates of 1, 5 and 10 Hz. This initiates with a rapid growth of intensity due to the significant elevation of the excited population as a consequence of the induced additional heat in the suspension. Figure 3(b) inset (i) shows LIF spectra of Capecitabine at different PRRs. Figure 3(b) inset (ii) depicts the energy of laser shot versus PRR. In fact, more repetition rates lead to the attenuation of the laser pulse energy according to inset (ii). As a result, the fluorescence intensity reduces gradually at high PRRs above 7 Hz mainly because of the internal restriction of ArF laser. Besides, more collisional events take place at higher repetition rates to enhance the quenching process leading to reduce the fluorescence emissions.

3.3. Measurement of fluorescence coefficients

Similarly we have carried out LIF for RdB fluorescence as reference dye. Figure 4(a) depicts the LIF signal in terms of RdB concentration. The LIF measurements undergo a sharp rise to the maximum emissions at Cp=12.5 µg/ml accompanying λmax=582 nm. It is worth noting that the fluorescent characteristics of the fluorophores of interest i.e, Capecitabine and RdB are taken into account as unique properties regardless of the excitation wavelength during LIF measurements [16].

 figure: Fig. 4.

Fig. 4. (a) LIF peak intensity in terms of RdB concentration ranging 3-50 (µg/ml) Inset: LIF spectra for different concentrations. (b) Emission wavelength versus RdB concentration emphasizing obvious spectral red shift, inset (i) The corresponding FWHM versus concentration, inset (ii) Normalized absorbance emission spectra. The overlapping spectral area is highlighted. Number of 50 trial measurements are averaged to find each datapoint.

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Figure 4(a) inset shows the LIF spectra at different RdB concentrations. By increasing the fluorophore concentration above Cp = 12.5 µg/ml, the amplitude of fluorescence signal falls down. In fact, there are a couple of competitive mechanisms as to the population of excited molecules enhance the fluorescence emission and then the quenching events become dominant mainly at dense solutions to reduce the signal intensity.

Figure 4(b) illustrates peak emission wavelength in terms of RdB concentration indicating a lucid red shift versus RdB concentration. Figure 4(b) inset (i) depicts the FWHM of fluorescence emission versus RdB concentration. Figure 4(b) inset (ii) plots the absorbance-emission spectra for RdB fluorophore. Note that the large hatched overlap area is highlighted due to the small stokes shift Δ=34 nm. According to Fig. 4(b) the spectral shift of 10 nm appears for the reference RdB fluorophore. This explains the fluorescence properties of Capecitabine against the known RdB fluorophore as reference. Table 1 tabulates the spectral properties of absorption and fluorescence measurements for RdB and Capecitabine. RdB fluorophore with smaller stokes shift (ΔRdB=34 nm vs ΔCap=202 nm) represents larger overlapping area leading to larger spectral red shift of fluorescence signal against those of Capecitabine. That mainly originates from the high reabsorption rate.

Tables Icon

Table 1. Spectral properties of LIF emission for Capecitabine and RdB as reference

On the other hand, Table 2 summarizes the intrinsic characteristics of the fluorophores of interest including mean refractive index, self-quenching parameter k, extinction coefficient α, concentration of fluorophore for maximum fluorescence emission Cp and quantum efficiency ηf. The purpose of Table 2 is to characterize further optical properties of Capecitabine and RdB fluorophores related to fluorescence spectra. RdB’s fluorescence signal If exhibits to be much stronger than that of Capecitabine due to its smaller stokes shift Δ and its notable quantum efficiency ηf which is in compliance with Eq. (2).

Tables Icon

Table 2. Fluorescence properties of Capecitabine versus RdB (Reference)

k (self-quenching parameter) and α (extinction coefficient) are determined using modified Beer- Lambert equation via the fitted curve of If versus concentration in LIF measurements of RdB and Capecitabine (Figs. 2.a and 4.a). Furthermore, Cp for RdB and Capecitabine are appointed in Figs. 2.a and 4.a. Note that larger kRdB (against kCap) is correlated to smaller Cp and vice versa. Moreover, ηf (Quantum efficiency) could be derived from Eq. (2). Mean refractive index (n) is the significant parameter to deal with optical path nd in course of light propagation where the reabsorption events take place. For instance, larger optical path along with more extinction coefficient could result in more reabsorption events leading to extra red shift. This may be one reason why bare RdB shows larger red shift than Capecitabine.

Assuming the linear dependence of the fluorescence emission with absorbed light at excitation wavelength, quantum yield can be measured for different chemodrugs [15,16]. Accordingly, quantum yield is determined using a reference fluorophore [15,16,29]. In Capecitabine case, RdB is assumed as reference fluorophore and quantum yield is calculated using the data given in Figs. 2(a)(Cap) and 4(a)(RdB) in terms of concentration and absorbance characteristics of both fluorophores respectively. Figure 5(a) shows the quantum yield ηf for reference RdB, Capecitabine (this work) and two other chemodrugs (Paclitaxel-PAC and Bleomycin-BLEO) in comparison [16,30]. According to Fig. 5(a), RdB, CAP, PAC and BLEO give out the calculated quantum yields of 70%, 7%, 7% and 4% respectively. Figure 5(b) illustrates the emission spectral shift for RdB, Capecitabine (this work) and two other chemodrugs (PAC and BLEO) of interest [16]. The larger spectral shift of RdB is given to be ∼ 10 nm, while the smaller spectral shifts of ∼ 6 and 7 nm occur for Capecitabine and Paclitaxel with similar reported quantum efficiencies. There is no spectral shift in the case of Bleomycin mainly due to its small overlap area [16].

 figure: Fig. 5.

Fig. 5. (a) Quantum yields and (b) spectral shifts of chemo-drugs of interest: Capecitabine, Paclitaxel and Bleomycin as biocompatible fluorophores against RdB as the reference fluorophore. Here, the fluorescence properties of Capecitabine is compared with other typical Chemodrugs (Paclitaxel and Bleomycin [16]) and RdB as reference fluorophore [30].

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3.4. LIF spectroscopy of (GO + Capecitabine) and (GO + RdB)

The nanoparticle/nanosheet carriers are added to the chemodrug of interest for the purpose of drug delivery. The fluorescence properties of Capecitabine in the presence of different densities of GO quencher are analyzed through successive measurements. Figure 6(a) illustrates the quenching LIF signal versus GO densities (2.5-250 µg/ml) at certain fluorophore concentration of Cp=2.5 mg/ml for (Cap + GO) suspension. Figure 6(a) inset depicts LIF spectra for various GO densities characterizing peak emission at λmax=409 nm. Figure 6(b) shows the emission wavelength versus GO density at Cp=2.5 mg/ml of Capecitabine and the inset represents the F0/F ratio in terms of GO density. GO sheets indicate the quenching effect associated with notable red shift of ∼ 7 nm in terms of GO concentration as Fig. 6(b). The quenching effects have been formerly reported on our previous reports too [7,21]. In fact, GO and ND additives attenuate the fluorescence signal of DOX chemodrug [7]. Furthermore, the GO nano carriers quench the LIF signal of Rd6G following an obvious spectral blue shift [21].

 figure: Fig. 6.

Fig. 6. (a) LIF peak intensity of Capecitabine in terms of GO densities ranging 2.5-50 (µg/ml) at certain 2.5 mg/ml Capecitabine concentration. Inset: Corresponding LIF spectra of Capecitabine at the attendance of different GO densities (b) Emission wavelength versus GO density at Cp=2.5 mg/ml indicating an obvious red shift. Inset: F0/F ratio in terms of variable GO densities. Number of 50 trial measurements are averaged to find each datapoint (c) Chemical structure of (GO + Cap) compound including π- π stacking and hydrogen bindings of GO with Capecitabine. Note that chemical structures are sketched using ChemDraw Ultra V.8.0 compound

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Here, dominant quenching events for LIF spectra of Capecitabine in the presence of GO nano sheets is due to hydrogen bonding and π-π stacking regarding the complex formations. According to Fig. 6(b), considerable fluorescence red shift is represented for (Cap + GO) suspension versus GO densities which slows down at dense concentrations. This arises from the fact that the excessive GO elongates optical path length leading to further reabsorption events; however the larger GO densities saturate the formation of (GO + Cap) compounds leading to slow down the red shift rate above 135 µg/ml. This is the explanation to support the evidence of reabsorption events leading to measurable red shift. Bare Capecitabine (with loaded GO) shows 6nm (7 nm) red shift in terms of concentration and the concentration of Capecitabine in target can be easily characterized with red shift measurement during LIF spectroscopy. As a result, the amount of chemodrug content penetrated in the tumor target can be assessed via the red shift measurement during LIF spectroscopy. That is why the spectral shift is very important regarding the correlation of this parameter with fluorophore content in tumor. Linear relation of F0/F ratio of Capecitabine fluorescence emission at 2.5 mg/ml concertation versus GO quencher is in good agreement with Stern-Volmer equation. This ascertains the static mode of fluorescence emission characterizing the quencher constant of $K_{GO}^{Cap} \approx$0.07. Whole data satisfies the S.V equation as well as modified S.V formalism with identical parameters. Consequently, the chemical affinity of GO with Capecitabine is graphically presented to show the possible structural complex formation of (GO + Capecitabine).

Figure 6(c) depicts the hydrogen bonds that are most likely formed during the dissolving procedure of GO in Capecitabine solvent. π- π stacking is also probable conjunction in this process. The quenching effect of GO is also due to acceptor function of the nano sheet in FRET phenomenon versus solvent fluorophore [31]. On the other hand, the red shift of fluorescence emission in (Capecitabine + GO) versus GO density arises from not only the dominant path length and reabsorption events but also the higher polarity of the media regarding the generated hydrogen bonds [32]. For instance, the fluorescence signal from the more polar media is usually faint and red shifted [31,33]. In fact, the dipolar relaxation of solvent molecules surrounding the fluorophore could cause the red shift in polar solvents due to energy dissipation during further dipole alignments [34,35].

Finally, the effect of GO additive on LIF spectra of RdB is investigated. The GO densities in the range of (20-1000 µg/ml) are added to typical RdB solution at (0.01 mg/ml). The green laser at 532 nm with 100 mW power is served as excitation source. Figure 7(a) plots LIF signal in terms of GO density at typical CRdB=0.01 mg/ml. Inset shows the LIF spectra at different GO densities characterizing λmax=582 nm. Figure 7(b) depicts emission wavelength versus GO density at similar RdB concentration. Inset illustrates F0/F ratio versus GO density at CRdB=0.01 mg/ml according to linear Stern-Volmer formalism. Here, the quenching events take place using GO sheets additive to RdB solution. However, GO additives do not show notable effect on fluorescence emission wavelength and it remains invariant versus GO density. The slope of linear relation of F0/F ratio versus GO concentration is used to obtain the quenching coefficient. Hence, the quenching coefficient is measured to be ∼ 0.012 at 0.01 mg/ml RdB concentration. Formerly, the faint blue shift is reported to appear in (Rd6G + GO) LIF spectra, while examining (ND + Rd6G) attests no evidence of spectral shift [21].

 figure: Fig. 7.

Fig. 7. (a) LIF peak intensity of RdB in terms of GO densities ranging 20-1000 (µg/ml) at certain 0.01 mg/ml RdB concentration. Inset: RdB LIF spectra of Capecitabine at the attendance of different GO densities (b) F0/F ratio of (RdB + GO) suspension in terms of variable GO densities. Inset: Fluorescence emission wavelength in terms of GO density. Number of 50 trial measurements are averaged to find each datapoint.

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In fact, Rd6G/RdB concentration is dominant parameter in favor of spectral shift measurement. For instance, the fluorescence spectra of (TiO2+RdB) at dense RdB concentration represent the sensible spectral shift, however examining a dilute RdB concentration leads to the negligible spectral shift [20]. Despite hydrogen bonds appear in (Cap + GO), however the loose bindings are formed in case of (RdB + GO). As a result, the emission wavelength of (RdB + GO) remains invariant at different GO densities regarding the faint compound formation while, the red shift takes place in (Cap + GO) due to the reabsorption events and strong compound formations. It is noteworthy that the initial red shift in (Cap + GO) is attributed to the large quenching coefficient $K_{GO}^{Cap}$=0.07, conversely no spectral shift takes place for (RdB + GO) with small $K_{GO}^{RdB}$ = 0.012.

4. Conclusion

Here we have shown that Capecitabine, as a common chemodrug, benefits strong properties which is investigated for the purpose of forthcoming applications in cancer therapy. Note that Capecitabine exhibits lucid fluorescence properties that could be used in simultaneous diagnosis and therapy based on LIF spectroscopy/imaging. These findings would be helpful to investigate the in vivo dynamics of carcinoma treatment during chemotherapy. The fluorescence characteristics of Capecitabine could assist the simultaneous diagnosis/treatment of cancerous tissues along with the tumoral imaging based on the interactions of the chemodrug with active sites of tissue to assess the instantaneous viability of unhealthy cells in synchronous chemotherapy.

This is a continuation of our previous works on the LIF of various chemodrugs such as, Navelbine, Paclitaxel, Bleomycin, Doxorubicin, Irinotecan and Gemcitabine. Here, Capecitabine exhibits notable fluorescence properties as to fluorescence signal varies with concentration accompanying the notable spectral red shift. Despite Capecitabine is characterized by three absorbance peaks over wide UV spectral range, however its fluorescence spectra is unique whether it is excited by 193 nm or other UV wavelengths. Effects of laser energy and pulse repetition rate on LIF spectra of Capecitabine are carefully examined. The LIF peak intensity and corresponding spectral shift of Capecitabine are determined under various pulse energies and different PRRs to find the optimal experimental configuration of measurements. We conclude that LIF spectroscopy is a reliable technique due to the undesirable nonlinear effects. The experimental data of fluorescence signals versus fluorophore concentrations fit the modified Beer-Lambert formalism. Self-quenching parameter k, extinction coefficient α, fluorescence spectral shifts and mean refractive index are determined for Capecitabine and RdB too. Quantum yield of Capecitabine against the fluorescence characteristics of RdB as the reference fluorophore is found. Furthermore, the quenching effect of GO on fluorescence properties of Capecitabine against RdB as reference fluorophore is verified and the quenching constants of$K_{GO}^{Cap}$and$K_{GO}^{RdB}$are extracted using Stern-Volmer formalism. Regarding the drug delivery concerns, the spectral red shift of (Capecitabine + GO) component as a fingerprint of GO concentrations is characterized.

We conclude that fluorescence red shift of Capecitabine is determined to be 6 nm versus reference fluorophore of RdB with 10 nm red shift. This originates from the smaller stokes shift of RdB, (ΔRdB=34 nm) against Capecitabine with (ΔCap=202 nm). Besides, the optimum laser energy and PRR for LIF measurement of Capecitabine are obtained at 230 mJ/Pulse and 7 Hz. Self-quenching coefficients of Capecitabine and RdB are measured to be (kCap=0.2 and kRdB = 1.18). Quantum yield of Capecitabine is calculated ∼ 7% versus that of RdB ∼ 70%. The higher quenching coefficient of GO in Cap ($K_{GO}^{Cap}$≈ 0.07) takes place accompanying a large red shift, regarding that of RdB + GO ($K_{GO}^{RdB}$≈ 0.012) with no spectral shift. The notable spectral shift of ∼ 7 nm corresponds to the hydrogen bonding and π- π interactions in (GO + Cap) structure. Furthermore, the red shift slows down at large GO concentration mainly due to the compound and conjugate formation at dense concentrations.

Acknowledgments

We are thankful to Dr. Zahra Shariatinia from Chemistry Department of Amirkabir University of Technology, Tehran, Iran, for her collaborations and useful discussions

Disclosures

The authors declare that there are no conflicts of interest related to this article.

References

1. S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011). [CrossRef]  

2. M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017). [CrossRef]  

3. M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991). [CrossRef]  

4. J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002). [CrossRef]  

5. F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008). [CrossRef]  

6. F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).

7. N. Hosseini Motlagh, P. Parvin, M. Refahizadeh, and A. Bavali, “Fluorescence properties of doxorubicin coupled carbon nanocarriers,” Appl. Opt. 56(26), 7498–7503 (2017). [CrossRef]  

8. Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015). [CrossRef]  

9. D.A. Krohn, T. MacDougall, and A. Mendez, “Fiber optic sensors: fundamentals and applications Bellingham,” WA: Spie Press (2014)

10. F. Ghasemi, P. Parvin, N. S. H. Motlagh, A. Amjadi, and S. Abachi, “” Laser induced breakdown spectroscopy and acoustic response techniques to discriminate healthy and cancerous breast tissues,”,” Appl. Opt. 55(29), 8227–8235 (2016). [CrossRef]  

11. P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011). [CrossRef]  

12. M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)

13. F. Ghasemi, P. Parvin, N. S. H. Motlagh, and S. Abachi, “LIF spectroscopy of stained malignant breast tissues,” Biomed. Opt. Express 8(2), 512–523 (2017). [CrossRef]  

14. F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017). [CrossRef]  

15. N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016). [CrossRef]  

16. N. S. H. Motlagh, P. Parvin, F. Ghasemi, and F. Atyabi, “Fluorescence properties of several chemotherapy drugs: Doxorubicin, Paclitaxel and Bleomycin,” Biomed. Opt. Express 7(6), 2400 (2016). [CrossRef]  

17. E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014). [CrossRef]  

18. I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004). [CrossRef]  

19. A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

20. A. Bavali, P. Parvin, S. Z. Mortazavi, M. Mohammadian, and M. R. Mousavi Pour, “Red/blue spectral shifts of laser-induced fluorescence emission due to different nanoparticle suspensions in various dye solutions,” Appl. Opt. 53(24), 5398–5409 (2014). [CrossRef]  

21. A. Bavali, P. Parvin, S. Z. Mortazavi, and S. S. Nourazar, “Laser induced fluorescence spectroscopy of various carbon nanostructures (GO, G and nanodiamond) in Rd6G solution,”,” Biomed. Opt. Express 6(5), 1679–1693 (2015). [CrossRef]  

22. S. K. Panigrahi and A. K. Mishra, “Study on the dependence of fluorescence intensity on optical density of solutions: the use of fluorescence observation field for inner filter effect corrections,” Photochem. Photobiol. Sci. 18(2), 583–591 (2019). [CrossRef]  

23. A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999). [CrossRef]  

24. J. R. Lakowicz, “Principles of fluorescence spectroscopy,” Springer Science & Business Media (2013)

25. A. Bavali, P. Parvin, M. Tavassoli, and M. R. Mohebbifar, “Angular distribution of laser-induced fluorescence emission of active dyes in scattering media,”,” Appl. Opt. 57(7), B32–B38 (2018). [CrossRef]  

26. M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5(1), 5722 (2014). [CrossRef]  

27. R. Altkorn and R. N. Zare, “Effects of saturation on laser-induced fluorescence measurements of population and polarization,” Ann. Rev. Phys. Chem. 35(1), 265–289 (1984). [CrossRef]  

28. W. W. Liu, “Intensity Clamping During Femtosecond Laser Filamentation,” Chin. J. Phys. 52(1), 465–489 (2014). [CrossRef]  

29. B. Valeur and M.N. Berberan-Santos, “Molecular Fluorescence: Principles and Applications,” Wiley-VCH (2002)

30. U. Brackmann. “Laser dyes,” Göttingen (Germany) Lambda Physik AG. D 37079 (2000).

31. P. Zheng and N. Wu, “Fluorescence and sensing applications of graphene oxide and graphene quantum dots: a review,” Chem. Asian J. 12(18), 2343–2353 (2017). [CrossRef]  

32. H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019). [CrossRef]  

33. I. A. Z. Al-Ansari, “Role of Solvent Polarity and Hydrogen-Bonding on Excited-State Fluorescence of 3-[(E)-{4-[Dimethylamino] benzylidene} amino]-2-naphthoic Acid (DMAMN): Isomerization vs Rotomerization,” J. Phys. Chem. A 122(7), 1838–1854 (2018). [CrossRef]  

34. B. Wardle, “Principles and applications of photochemistry,” John Wiley & Sons (2009)

35. T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998). [CrossRef]  

References

  • View by:

  1. S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
    [Crossref]
  2. M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017).
    [Crossref]
  3. M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
    [Crossref]
  4. J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
    [Crossref]
  5. F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
    [Crossref]
  6. F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).
  7. N. Hosseini Motlagh, P. Parvin, M. Refahizadeh, and A. Bavali, “Fluorescence properties of doxorubicin coupled carbon nanocarriers,” Appl. Opt. 56(26), 7498–7503 (2017).
    [Crossref]
  8. Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
    [Crossref]
  9. D.A. Krohn, T. MacDougall, and A. Mendez, “Fiber optic sensors: fundamentals and applications Bellingham,” WA: Spie Press (2014)
  10. F. Ghasemi, P. Parvin, N. S. H. Motlagh, A. Amjadi, and S. Abachi, “” Laser induced breakdown spectroscopy and acoustic response techniques to discriminate healthy and cancerous breast tissues,”,” Appl. Opt. 55(29), 8227–8235 (2016).
    [Crossref]
  11. P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
    [Crossref]
  12. M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)
  13. F. Ghasemi, P. Parvin, N. S. H. Motlagh, and S. Abachi, “LIF spectroscopy of stained malignant breast tissues,” Biomed. Opt. Express 8(2), 512–523 (2017).
    [Crossref]
  14. F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
    [Crossref]
  15. N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016).
    [Crossref]
  16. N. S. H. Motlagh, P. Parvin, F. Ghasemi, and F. Atyabi, “Fluorescence properties of several chemotherapy drugs: Doxorubicin, Paclitaxel and Bleomycin,” Biomed. Opt. Express 7(6), 2400 (2016).
    [Crossref]
  17. E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
    [Crossref]
  18. I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
    [Crossref]
  19. A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).
  20. A. Bavali, P. Parvin, S. Z. Mortazavi, M. Mohammadian, and M. R. Mousavi Pour, “Red/blue spectral shifts of laser-induced fluorescence emission due to different nanoparticle suspensions in various dye solutions,” Appl. Opt. 53(24), 5398–5409 (2014).
    [Crossref]
  21. A. Bavali, P. Parvin, S. Z. Mortazavi, and S. S. Nourazar, “Laser induced fluorescence spectroscopy of various carbon nanostructures (GO, G and nanodiamond) in Rd6G solution,”,” Biomed. Opt. Express 6(5), 1679–1693 (2015).
    [Crossref]
  22. S. K. Panigrahi and A. K. Mishra, “Study on the dependence of fluorescence intensity on optical density of solutions: the use of fluorescence observation field for inner filter effect corrections,” Photochem. Photobiol. Sci. 18(2), 583–591 (2019).
    [Crossref]
  23. A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
    [Crossref]
  24. J. R. Lakowicz, “Principles of fluorescence spectroscopy,” Springer Science & Business Media (2013)
  25. A. Bavali, P. Parvin, M. Tavassoli, and M. R. Mohebbifar, “Angular distribution of laser-induced fluorescence emission of active dyes in scattering media,”,” Appl. Opt. 57(7), B32–B38 (2018).
    [Crossref]
  26. M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5(1), 5722 (2014).
    [Crossref]
  27. R. Altkorn and R. N. Zare, “Effects of saturation on laser-induced fluorescence measurements of population and polarization,” Ann. Rev. Phys. Chem. 35(1), 265–289 (1984).
    [Crossref]
  28. W. W. Liu, “Intensity Clamping During Femtosecond Laser Filamentation,” Chin. J. Phys. 52(1), 465–489 (2014).
    [Crossref]
  29. B. Valeur and M.N. Berberan-Santos, “Molecular Fluorescence: Principles and Applications,” Wiley-VCH (2002)
  30. U. Brackmann. “Laser dyes,” Göttingen (Germany) Lambda Physik AG. D 37079 (2000).
  31. P. Zheng and N. Wu, “Fluorescence and sensing applications of graphene oxide and graphene quantum dots: a review,” Chem. Asian J. 12(18), 2343–2353 (2017).
    [Crossref]
  32. H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
    [Crossref]
  33. I. A. Z. Al-Ansari, “Role of Solvent Polarity and Hydrogen-Bonding on Excited-State Fluorescence of 3-[(E)-{4-[Dimethylamino] benzylidene} amino]-2-naphthoic Acid (DMAMN): Isomerization vs Rotomerization,” J. Phys. Chem. A 122(7), 1838–1854 (2018).
    [Crossref]
  34. B. Wardle, “Principles and applications of photochemistry,” John Wiley & Sons (2009)
  35. T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
    [Crossref]

2019 (2)

S. K. Panigrahi and A. K. Mishra, “Study on the dependence of fluorescence intensity on optical density of solutions: the use of fluorescence observation field for inner filter effect corrections,” Photochem. Photobiol. Sci. 18(2), 583–591 (2019).
[Crossref]

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

2018 (2)

I. A. Z. Al-Ansari, “Role of Solvent Polarity and Hydrogen-Bonding on Excited-State Fluorescence of 3-[(E)-{4-[Dimethylamino] benzylidene} amino]-2-naphthoic Acid (DMAMN): Isomerization vs Rotomerization,” J. Phys. Chem. A 122(7), 1838–1854 (2018).
[Crossref]

A. Bavali, P. Parvin, M. Tavassoli, and M. R. Mohebbifar, “Angular distribution of laser-induced fluorescence emission of active dyes in scattering media,”,” Appl. Opt. 57(7), B32–B38 (2018).
[Crossref]

2017 (5)

P. Zheng and N. Wu, “Fluorescence and sensing applications of graphene oxide and graphene quantum dots: a review,” Chem. Asian J. 12(18), 2343–2353 (2017).
[Crossref]

M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017).
[Crossref]

N. Hosseini Motlagh, P. Parvin, M. Refahizadeh, and A. Bavali, “Fluorescence properties of doxorubicin coupled carbon nanocarriers,” Appl. Opt. 56(26), 7498–7503 (2017).
[Crossref]

F. Ghasemi, P. Parvin, N. S. H. Motlagh, and S. Abachi, “LIF spectroscopy of stained malignant breast tissues,” Biomed. Opt. Express 8(2), 512–523 (2017).
[Crossref]

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

2016 (3)

2015 (2)

Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
[Crossref]

A. Bavali, P. Parvin, S. Z. Mortazavi, and S. S. Nourazar, “Laser induced fluorescence spectroscopy of various carbon nanostructures (GO, G and nanodiamond) in Rd6G solution,”,” Biomed. Opt. Express 6(5), 1679–1693 (2015).
[Crossref]

2014 (5)

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

A. Bavali, P. Parvin, S. Z. Mortazavi, M. Mohammadian, and M. R. Mousavi Pour, “Red/blue spectral shifts of laser-induced fluorescence emission due to different nanoparticle suspensions in various dye solutions,” Appl. Opt. 53(24), 5398–5409 (2014).
[Crossref]

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

W. W. Liu, “Intensity Clamping During Femtosecond Laser Filamentation,” Chin. J. Phys. 52(1), 465–489 (2014).
[Crossref]

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5(1), 5722 (2014).
[Crossref]

2011 (2)

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
[Crossref]

2008 (1)

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

2004 (1)

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

2002 (1)

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

1999 (1)

A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
[Crossref]

1998 (1)

T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
[Crossref]

1991 (1)

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

1984 (1)

R. Altkorn and R. N. Zare, “Effects of saturation on laser-induced fluorescence measurements of population and polarization,” Ann. Rev. Phys. Chem. 35(1), 265–289 (1984).
[Crossref]

Abachi, S.

Al-Ansari, I. A. Z.

I. A. Z. Al-Ansari, “Role of Solvent Polarity and Hydrogen-Bonding on Excited-State Fluorescence of 3-[(E)-{4-[Dimethylamino] benzylidene} amino]-2-naphthoic Acid (DMAMN): Isomerization vs Rotomerization,” J. Phys. Chem. A 122(7), 1838–1854 (2018).
[Crossref]

Alhaique, F.

A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
[Crossref]

Altkorn, R.

R. Altkorn and R. N. Zare, “Effects of saturation on laser-induced fluorescence measurements of population and polarization,” Ann. Rev. Phys. Chem. 35(1), 265–289 (1984).
[Crossref]

Amadori, D.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Amjadi, A.

Anwar, Sh.

Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
[Crossref]

Atyabi, F.

N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016).
[Crossref]

N. S. H. Motlagh, P. Parvin, F. Ghasemi, and F. Atyabi, “Fluorescence properties of several chemotherapy drugs: Doxorubicin, Paclitaxel and Bleomycin,” Biomed. Opt. Express 7(6), 2400 (2016).
[Crossref]

Bagatolli, L.

T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
[Crossref]

Barone, C.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Bavali, A.

Berberan-Santos, M.N.

B. Valeur and M.N. Berberan-Santos, “Molecular Fluorescence: Principles and Applications,” Wiley-VCH (2002)

Bertetto, O.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Bonnabry, P.

S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
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U. Brackmann. “Laser dyes,” Göttingen (Germany) Lambda Physik AG. D 37079 (2000).

Buchner, P.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Bünermann, O.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
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Catalin, J.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
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Ciccolini, J.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
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Conde, O. M.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
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Czejka, M.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Di Costanzo, F.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Ding, F.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Dorenkamp, Y.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Etienne, M. C.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

Farkouh, A.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Firdous, A. H.

Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
[Crossref]

Fischel, J. L.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

Fitatiuk, J.

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

Formento, P.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

Fujimura, T.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Fushida, S.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
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Gather, M. C.

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5(1), 5722 (2014).
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Georgopoulos, A.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Gerstner, J. B.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Ghasemi, F.

F. Ghasemi, P. Parvin, N. S. H. Motlagh, and S. Abachi, “LIF spectroscopy of stained malignant breast tissues,” Biomed. Opt. Express 8(2), 512–523 (2017).
[Crossref]

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016).
[Crossref]

N. S. H. Motlagh, P. Parvin, F. Ghasemi, and F. Atyabi, “Fluorescence properties of several chemotherapy drugs: Doxorubicin, Paclitaxel and Bleomycin,” Biomed. Opt. Express 7(6), 2400 (2016).
[Crossref]

F. Ghasemi, P. Parvin, N. S. H. Motlagh, A. Amjadi, and S. Abachi, “” Laser induced breakdown spectroscopy and acoustic response techniques to discriminate healthy and cancerous breast tissues,”,” Appl. Opt. 55(29), 8227–8235 (2016).
[Crossref]

F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).

Gratton, E.

T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
[Crossref]

Gruenberger, B.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Harris, B. T.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Hosseini Motlagh, N.

N. Hosseini Motlagh, P. Parvin, M. Refahizadeh, and A. Bavali, “Fluorescence properties of doxorubicin coupled carbon nanocarriers,” Appl. Opt. 56(26), 7498–7503 (2017).
[Crossref]

F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).

Jelvani, S.

N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016).
[Crossref]

Jiang, H.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Kammler, M.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Kandratsenka, A.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Kardinal, C. G.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Karimi, R.

F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).

Kaza, M.

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

keraji, M.

M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)

Kim, A.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Krasnowska, E. K.

T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
[Crossref]

Krohn, D.A.

D.A. Krohn, T. MacDougall, and A. Mendez, “Fiber optic sensors: fundamentals and applications Bellingham,” WA: Spie Press (2014)

Krook, J. E.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Labianca, R.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Lakowicz, J. R.

J. R. Lakowicz, “Principles of fluorescence spectroscopy,” Springer Science & Business Media (2013)

Leblond, F.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Levitt, R.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Li, M.

M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017).
[Crossref]

M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017).
[Crossref]

Liu, W. W.

W. W. Liu, “Intensity Clamping During Femtosecond Laser Filamentation,” Chin. J. Phys. 52(1), 465–489 (2014).
[Crossref]

Longo, F.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Luppi, G.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

MacDougall, T.

D.A. Krohn, T. MacDougall, and A. Mendez, “Fiber optic sensors: fundamentals and applications Bellingham,” WA: Spie Press (2014)

Mailliard, J. A.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Manby, F. R.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Mehravaran, H.

M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)

Memoli, A.

A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
[Crossref]

Mendez, A.

D.A. Krohn, T. MacDougall, and A. Mendez, “Fiber optic sensors: fundamentals and applications Bellingham,” WA: Spie Press (2014)

Merlano, M. C.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Milano, G.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

Miller, T. F.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Mirzaee, F.H.

M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)

Mishra, A. K.

S. K. Panigrahi and A. K. Mishra, “Study on the dependence of fluorescence intensity on optical density of solutions: the use of fluorescence observation field for inner filter effect corrections,” Photochem. Photobiol. Sci. 18(2), 583–591 (2019).
[Crossref]

Miwa, K.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Mohammadian, M.

Mohebbifar, M. R.

A. Bavali, P. Parvin, M. Tavassoli, and M. R. Mohebbifar, “Angular distribution of laser-induced fluorescence emission of active dyes in scattering media,”,” Appl. Opt. 57(7), B32–B38 (2018).
[Crossref]

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

Morita, A.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Mortazavi, S. Z.

Motlagh, N. S. H.

Mousavi Pour, M. R.

Nagai, N.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Nawaz, M.

Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
[Crossref]

Ninomiya, I.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Nishimura, G.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Nourazar, S. S.

Nussbaumer, S.

S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
[Crossref]

O’Connell, M. J.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Ohta, T.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Palermiti, L. G.

A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
[Crossref]

Panigrahi, S. K.

S. K. Panigrahi and A. K. Mishra, “Study on the dependence of fluorescence intensity on optical density of solutions: the use of fluorescence observation field for inner filter effect corrections,” Photochem. Photobiol. Sci. 18(2), 583–591 (2019).
[Crossref]

Parasassi, T.

T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
[Crossref]

Parvin, P.

A. Bavali, P. Parvin, M. Tavassoli, and M. R. Mohebbifar, “Angular distribution of laser-induced fluorescence emission of active dyes in scattering media,”,” Appl. Opt. 57(7), B32–B38 (2018).
[Crossref]

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

N. Hosseini Motlagh, P. Parvin, M. Refahizadeh, and A. Bavali, “Fluorescence properties of doxorubicin coupled carbon nanocarriers,” Appl. Opt. 56(26), 7498–7503 (2017).
[Crossref]

F. Ghasemi, P. Parvin, N. S. H. Motlagh, and S. Abachi, “LIF spectroscopy of stained malignant breast tissues,” Biomed. Opt. Express 8(2), 512–523 (2017).
[Crossref]

F. Ghasemi, P. Parvin, N. S. H. Motlagh, A. Amjadi, and S. Abachi, “” Laser induced breakdown spectroscopy and acoustic response techniques to discriminate healthy and cancerous breast tissues,”,” Appl. Opt. 55(29), 8227–8235 (2016).
[Crossref]

N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016).
[Crossref]

N. S. H. Motlagh, P. Parvin, F. Ghasemi, and F. Atyabi, “Fluorescence properties of several chemotherapy drugs: Doxorubicin, Paclitaxel and Bleomycin,” Biomed. Opt. Express 7(6), 2400 (2016).
[Crossref]

A. Bavali, P. Parvin, S. Z. Mortazavi, and S. S. Nourazar, “Laser induced fluorescence spectroscopy of various carbon nanostructures (GO, G and nanodiamond) in Rd6G solution,”,” Biomed. Opt. Express 6(5), 1679–1693 (2015).
[Crossref]

A. Bavali, P. Parvin, S. Z. Mortazavi, M. Mohammadian, and M. R. Mousavi Pour, “Red/blue spectral shifts of laser-induced fluorescence emission due to different nanoparticle suspensions in various dye solutions,” Appl. Opt. 53(24), 5398–5409 (2014).
[Crossref]

F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).

M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)

Paulsen, K. D.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Pawinski, T.

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

Piórkowska, E.

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

Poon, M. A.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Ravasio, R.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Razzaghi, M. R.

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

Refahizadeh, M.

Rehman, A. U.

Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
[Crossref]

Reif, J.

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

Roberts, D. W.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Rostagno, P.

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

Rudzki, P. J.

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

Scheithauer, W.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Schueller, J.

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Sobrero, A.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Souverain, S. F.

S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
[Crossref]

Szlaska, I.

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

Takino, T.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Tavassoli, M.

Terada, I.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Travagli, V.

A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
[Crossref]

Tschetter, L. K.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Valdes, P. A.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Valeur, B.

B. Valeur and M.N. Berberan-Santos, “Molecular Fluorescence: Principles and Applications,” Wiley-VCH (2002)

Veuthey, J. L.

S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
[Crossref]

Vinante, O.

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Wardle, B.

B. Wardle, “Principles and applications of photochemistry,” John Wiley & Sons (2009)

Wieand, H. S.

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

Wilson, B. C.

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

Wodtke, A. M.

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Wu, N.

P. Zheng and N. Wu, “Fluorescence and sensing applications of graphene oxide and graphene quantum dots: a review,” Chem. Asian J. 12(18), 2343–2353 (2017).
[Crossref]

Yoshizumi, T.

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

Yun, S. H.

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5(1), 5722 (2014).
[Crossref]

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R. Altkorn and R. N. Zare, “Effects of saturation on laser-induced fluorescence measurements of population and polarization,” Ann. Rev. Phys. Chem. 35(1), 265–289 (1984).
[Crossref]

Zhang, N.

M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017).
[Crossref]

Zheng, P.

P. Zheng and N. Wu, “Fluorescence and sensing applications of graphene oxide and graphene quantum dots: a review,” Chem. Asian J. 12(18), 2343–2353 (2017).
[Crossref]

Ann. Rev. Phys. Chem. (1)

R. Altkorn and R. N. Zare, “Effects of saturation on laser-induced fluorescence measurements of population and polarization,” Ann. Rev. Phys. Chem. 35(1), 265–289 (1984).
[Crossref]

Anticancer Res. (1)

A. Farkouh, W. Scheithauer, P. Buchner, A. Georgopoulos, J. Schueller, B. Gruenberger, and M. Czejka, “Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab,” Anticancer Res. 34(7), 3669–3673 (2014).

Appl. Opt. (4)

Biomed. Opt. Express (3)

Br. J. Cancer (1)

J. L. Fischel, P. Formento, J. Ciccolini, P. Rostagno, M. C. Etienne, J. Catalin, and G. Milano, “Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity,” Br. J. Cancer 86(7), 1162–1168 (2002).
[Crossref]

Chem. Asian J. (1)

P. Zheng and N. Wu, “Fluorescence and sensing applications of graphene oxide and graphene quantum dots: a review,” Chem. Asian J. 12(18), 2343–2353 (2017).
[Crossref]

Chin. J. Phys. (1)

W. W. Liu, “Intensity Clamping During Femtosecond Laser Filamentation,” Chin. J. Phys. 52(1), 465–489 (2014).
[Crossref]

Clin. Drug Invest. (1)

F. Di Costanzo, R. Ravasio, A. Sobrero, O. Bertetto, O. Vinante, G. Luppi, R. Labianca, D. Amadori, C. Barone, M. C. Merlano, and F. Longo, “Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes’ C colon cancer,” Clin. Drug Invest. 28(10), 645–655 (2008).
[Crossref]

Int. J. Cancer (1)

I. Ninomiya, I. Terada, T. Yoshizumi, T. Takino, N. Nagai, A. Morita, S. Fushida, G. Nishimura, T. Fujimura, T. Ohta, and K. Miwa, “Anti-metastatic effect of capecitabine on human colon cancer xenografts in nude mouse rectum,” Int. J. Cancer 112(1), 135–142 (2004).
[Crossref]

J. Biomed. Opt. (1)

P. A. Valdes, F. Leblond, K. D. Paulsen, A. Kim, B. C. Wilson, O. M. Conde, B. T. Harris, and D. W. Roberts, “Combined fluorescence and reflectance spectroscopy for in vivo quantification of cancer biomarkers in low-and high-grade glioma surgery,” J. Biomed. Opt. 16(11), 116007 (2011).
[Crossref]

J. Clin. Oncol. (1)

M. A. Poon, M. J. O’Connell, H. S. Wieand, J. E. Krook, J. B. Gerstner, L. K. Tschetter, R. Levitt, C. G. Kardinal, and J. A. Mailliard, “Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer,” J. Clin. Oncol. 9(11), 1967–1972 (1991).
[Crossref]

J. Fluoresc. (1)

T. Parasassi, E. K. Krasnowska, L. Bagatolli, and E. Gratton, “Laurdan and Prodan as polarity-sensitive fluorescent membrane probes,” J. Fluoresc. 8(4), 365–373 (1998).
[Crossref]

J. Laser Appl. (1)

F. Ghasemi, P. Parvin, J. Reif, S. Abachi, M. R. Mohebbifar, and M. R. Razzaghi, “Laser induced breakdown spectroscopy for the diagnosis of several malignant tissue samples,”,” J. Laser Appl. 29(4), 042005 (2017).
[Crossref]

J. Pharm. Biomed. Anal. (1)

A. Memoli, L. G. Palermiti, V. Travagli, and F. Alhaique, “Effects of surfactants on the spectral behaviour of calcein (II): a method of evaluation,” J. Pharm. Biomed. Anal. 19(3-4), 627–632 (1999).
[Crossref]

J. Phys. Chem. A (1)

I. A. Z. Al-Ansari, “Role of Solvent Polarity and Hydrogen-Bonding on Excited-State Fluorescence of 3-[(E)-{4-[Dimethylamino] benzylidene} amino]-2-naphthoic Acid (DMAMN): Isomerization vs Rotomerization,” J. Phys. Chem. A 122(7), 1838–1854 (2018).
[Crossref]

Laser Phys. Lett. (2)

N. S. H. Motlagh, P. Parvin, F. Ghasemi, F. Atyabi, and S. Jelvani, “Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine,” Laser Phys. Lett. 13(7), 075604 (2016).
[Crossref]

Sh. Anwar, A. H. Firdous, A. U. Rehman, and M. Nawaz, “Optical diagnostic of breast cancer using Raman polarimetric and fluorescence spectroscopy,” Laser Phys. Lett. 12(4), 045601 (2015).
[Crossref]

Nat. Commun. (1)

M. C. Gather and S. H. Yun, “Bio-optimized energy transfer in densely packed fluorescent protein enables near-maximal luminescence and solid-state lasers,” Nat. Commun. 5(1), 5722 (2014).
[Crossref]

Pharmazie (1)

E. Piórkowska, M. Kaza, J. Fitatiuk, I. Szlaska, T. Pawinski, and P. J. Rudzki, “Rapid and simplified HPLC-UV method with on-line wavelengths switching for determination of capecitabine in human plasma,” Pharmazie 69(7), 500–505 (2014).
[Crossref]

Photochem. Photobiol. Sci. (1)

S. K. Panigrahi and A. K. Mishra, “Study on the dependence of fluorescence intensity on optical density of solutions: the use of fluorescence observation field for inner filter effect corrections,” Photochem. Photobiol. Sci. 18(2), 583–591 (2019).
[Crossref]

Science (1)

H. Jiang, M. Kammler, F. Ding, Y. Dorenkamp, F. R. Manby, A. M. Wodtke, T. F. Miller, A. Kandratsenka, and O. Bünermann, “Imaging covalent bond formation by H atom scattering from graphene,” Science 364(6438), 379–382 (2019).
[Crossref]

Talanta (1)

S. Nussbaumer, P. Bonnabry, J. L. Veuthey, and S. F. Souverain, “Analysis of anticancer drugs: a review,” Talanta 85(5), 2265–2289 (2011).
[Crossref]

Trop. J. Pharm. Res. (1)

M. Li, N. Zhang, and M. Li, “Capecitabine treatment of HCT-15 colon cancer cells induces apoptosis via mitochondrial pathway,” Trop. J. Pharm. Res. 16(7), 1529–1536 (2017).
[Crossref]

Other (7)

F. Ghasemi, P. Parvin, N. Hosseini Motlagh, A. Bavali, and R. Karimi, “Optical spectroscopic methods to discriminate in- Vitro Hodgkin cancerous and normal tissues,” Optical Molecular Probes, Imaging and Drug Delivery.Optical Society of America (pp. JT3A-40) (2015).

D.A. Krohn, T. MacDougall, and A. Mendez, “Fiber optic sensors: fundamentals and applications Bellingham,” WA: Spie Press (2014)

M. keraji, F.H. Mirzaee, A. Bavali, H. Mehravaran, and P. Parvin, “Laser induced fluorescence and breakdown spectroscopy and acoustic response, to discriminate malignant and normal tissues,” Proc. of OSA-SPIE Germany (p. 87980A) (2013)

B. Wardle, “Principles and applications of photochemistry,” John Wiley & Sons (2009)

J. R. Lakowicz, “Principles of fluorescence spectroscopy,” Springer Science & Business Media (2013)

B. Valeur and M.N. Berberan-Santos, “Molecular Fluorescence: Principles and Applications,” Wiley-VCH (2002)

U. Brackmann. “Laser dyes,” Göttingen (Germany) Lambda Physik AG. D 37079 (2000).

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Figures (7)

Fig. 1.
Fig. 1. (a) Experimental set-up for LIF measurement of Capecitabine, including coherent excitation source of ArF laser, detector with triggered modular spectrometer and the optical collimating lens (b) UV-VIS absorption spectra of Capecitabine in different concentration characterizing three absorbance peaks at 216, 237 and 302 nm. Inset: absorption peak intensity versus fluorophore concentrations (c) Normalized overlapping area between absorption and LIF spectra as well as absorbance peak at 216 nm, emission peak at 408 nm and stokes shift Δ=202 nm. Note: Cuvette length is 1 cm.
Fig. 2.
Fig. 2. (a) LIF peak intensity versus Capecitabine concentration ranging 0.25-10 (mg/ml). Inset: Corresponding LIF spectra of different concentrations b) Emission wavelength in terms of Capecitabine concentration indicating a lucid red shift of 6 nm. This is mainly due to the reabsorption events that arises from the spectral overlap of absorbance and fluorescence emission. Inset: FWHM of LIF signals versus concentration. Note that FWHM reduction arises from the shrinkage of overlapping area that strongly affects the fluorescence properties of Capecitabine to slow down the rate of red shift at dense concentrations. Number of 50 trial measurements are averaged to find each datapoint.
Fig. 3.
Fig. 3. (a) Capecitabine fluorescence signal intensity versus pulse energy of ArF laser, inset (i) LIF spectra at different pulse energies ranging 130-270 mJ, inset (ii) Emission wavelength versus pulse energy (b) LIF peak intensity in terms of PRR of ArF laser. Inset (i) Capecitabine LIF spectra versus PRR (1-10 Hz) inset (ii) output pulsed energy in different PRRs. Number of 50 trial measurements are averaged to find each datapoint.
Fig. 4.
Fig. 4. (a) LIF peak intensity in terms of RdB concentration ranging 3-50 (µg/ml) Inset: LIF spectra for different concentrations. (b) Emission wavelength versus RdB concentration emphasizing obvious spectral red shift, inset (i) The corresponding FWHM versus concentration, inset (ii) Normalized absorbance emission spectra. The overlapping spectral area is highlighted. Number of 50 trial measurements are averaged to find each datapoint.
Fig. 5.
Fig. 5. (a) Quantum yields and (b) spectral shifts of chemo-drugs of interest: Capecitabine, Paclitaxel and Bleomycin as biocompatible fluorophores against RdB as the reference fluorophore. Here, the fluorescence properties of Capecitabine is compared with other typical Chemodrugs (Paclitaxel and Bleomycin [16]) and RdB as reference fluorophore [30].
Fig. 6.
Fig. 6. (a) LIF peak intensity of Capecitabine in terms of GO densities ranging 2.5-50 (µg/ml) at certain 2.5 mg/ml Capecitabine concentration. Inset: Corresponding LIF spectra of Capecitabine at the attendance of different GO densities (b) Emission wavelength versus GO density at Cp=2.5 mg/ml indicating an obvious red shift. Inset: F0/F ratio in terms of variable GO densities. Number of 50 trial measurements are averaged to find each datapoint (c) Chemical structure of (GO + Cap) compound including π- π stacking and hydrogen bindings of GO with Capecitabine. Note that chemical structures are sketched using ChemDraw Ultra V.8.0 compound
Fig. 7.
Fig. 7. (a) LIF peak intensity of RdB in terms of GO densities ranging 20-1000 (µg/ml) at certain 0.01 mg/ml RdB concentration. Inset: RdB LIF spectra of Capecitabine at the attendance of different GO densities (b) F0/F ratio of (RdB + GO) suspension in terms of variable GO densities. Inset: Fluorescence emission wavelength in terms of GO density. Number of 50 trial measurements are averaged to find each datapoint.

Tables (2)

Tables Icon

Table 1. Spectral properties of LIF emission for Capecitabine and RdB as reference

Tables Icon

Table 2. Fluorescence properties of Capecitabine versus RdB (Reference)

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

I f = β ( 1 10 α C l ) e k C l
I f = I a η f λ f ¯ λ a b s = I a η f λ f ¯ Δ + λ f
F 0 / F = 1 + K [ Q ]

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