Abstract

Current imaging techniques capable of tracking nanoparticles in vivo supply either a large field of view or cellular resolution, but not both. Here, we demonstrate a multimodality imaging platform of optical coherence tomography (OCT) techniques for high resolution, wide field of view in vivo imaging of nanoparticles. This platform includes the first in vivo images of nanoparticle pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying images of microvascular and tissue morphology. Gold nanorods (51.8 ± 8.1 nm by 15.2 ± 3.3 nm) were intravenously injected into mice, and their accumulation into mammary tumors was non-invasively imaged in vivo in three dimensions over 24 hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold nanorods reached peak distribution throughout the tumors by 16 hours, and remained well-dispersed up to 24 hours post-injection. In contrast, the overall accumulation of gold nanorods within the tumors peaked around 16 hours post-injection. The accumulation of gold nanorods within the tumors was validated post-mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies.

© 2014 Optical Society of America

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2013 (3)

2012 (6)

C. Pache, N. L. Bocchio, A. Bouwens, M. Villiger, C. Berclaz, J. Goulley, M. I. Gibson, C. Santschi, and T. Lasser, “Fast three-dimensional imaging of gold nanoparticles in living cells with photothermal optical lock-in Optical Coherence Microscopy,” Opt. Express20(19), 21385–21399 (2012).
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H. M. Subhash, H. Xie, J. W. Smith, and O. J. T. McCarty, “Optical detection of indocyanine green encapsulated biocompatible poly (lactic-co-glycolic) acid nanoparticles with photothermal optical coherence tomography,” Opt. Lett.37(5), 981–983 (2012).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

2011 (5)

J. Fang, H. Nakamura, and H. Maeda, “The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect,” Adv. Drug Deliv. Rev.63(3), 136–151 (2011).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

A. S. Thakor, J. Jokerst, C. Zavaleta, T. F. Massoud, and S. S. Gambhir, “Gold Nanoparticles: A Revival in Precious Metal Administration to Patients,” Nano Lett.11(10), 4029–4036 (2011).
[CrossRef] [PubMed]

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[CrossRef] [PubMed]

G. Y. Guan, R. Reif, Z. H. Huang, and R. K. K. Wang, “Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography,” J. Biomed. Opt.16(12), 126003 (2011).
[CrossRef] [PubMed]

2010 (6)

S. K. Libutti, G. F. Paciotti, A. A. Byrnes, H. R. Alexander, W. E. Gannon, M. Walker, G. D. Seidel, N. Yuldasheva, and L. Tamarkin, “Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine,” Clin. Cancer Res.16(24), 6139–6149 (2010).
[CrossRef] [PubMed]

J. Park, A. Estrada, J. A. Schwartz, P. Diagaradjane, S. Krishnan, A. K. Dunn, and J. W. Tunnell, “Intra-Organ Biodistribution of Gold Nanoparticles Using Intrinsic Two-photon Induced Photoluminescence,” Lasers Surg. Med.42(7), 630–639 (2010).
[CrossRef] [PubMed]

A. S. Paranjape, R. Kuranov, S. Baranov, L. L. Ma, J. W. Villard, T. Y. Wang, K. V. Sokolov, M. D. Feldman, K. P. Johnston, and T. E. Milner, “Depth resolved photothermal OCT detection of macrophages in tissue using nanorose,” Biomed. Opt. Express1(1), 2–16 (2010).
[CrossRef] [PubMed]

S. Moon, S. W. Lee, and Z. P. Chen, “Reference spectrum extraction and fixed-pattern noise removal in optical coherence tomography,” Opt. Express18(24), 24395–24404 (2010).
[CrossRef] [PubMed]

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
[CrossRef] [PubMed]

D. Jacob, R. L. Shelton, and B. E. Applegate, “Fourier domain pump-probe optical coherence tomography imaging of Melanin,” Opt. Express18(12), 12399–12410 (2010).
[CrossRef] [PubMed]

2009 (8)

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

J. A. Schwartz, A. M. Shetty, R. E. Price, R. J. Stafford, J. C. Wang, R. K. Uthamanthil, K. Pham, R. J. McNichols, C. L. Coleman, and J. D. Payne, “Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model,” Cancer Res.69(4), 1659–1667 (2009).
[CrossRef] [PubMed]

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

C. L. Zavaleta, B. R. Smith, I. Walton, W. Doering, G. Davis, B. Shojaei, M. J. Natan, and S. S. Gambhir, “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.106(32), 13511–13516 (2009).
[CrossRef] [PubMed]

L. Tong, Q. S. Wei, A. Wei, and J. X. Cheng, “Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects,” Photochem. Photobiol.85(1), 21–32 (2009).
[CrossRef] [PubMed]

Y. Akiyama, T. Mori, Y. Katayama, and T. Niidome, “The effects of PEG grafting level and injection dose on gold nanorod biodistribution in the tumor-bearing mice,” J. Control. Release139(1), 81–84 (2009).
[CrossRef] [PubMed]

S. D. Perrault, C. Walkey, T. Jennings, H. C. Fischer, and W. C. W. Chan, “Mediating Tumor Targeting Efficiency of Nanoparticles Through Design,” Nano Lett.9(5), 1909–1915 (2009).
[CrossRef] [PubMed]

2008 (5)

A. Mariampillai, B. A. Standish, E. H. Moriyama, M. Khurana, N. R. Munce, M. K. K. Leung, J. Jiang, A. Cable, B. C. Wilson, I. A. Vitkin, and V. X. D. Yang, “Speckle variance detection of microvasculature using swept-source optical coherence tomography,” Opt. Lett.33(13), 1530–1532 (2008).
[CrossRef] [PubMed]

X. M. Qian, X. H. Peng, D. O. Ansari, Q. Yin-Goen, G. Z. Chen, D. M. Shin, L. Yang, A. N. Young, M. D. Wang, and S. M. Nie, “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags,” Nat. Biotechnol.26(1), 83–90 (2008).
[CrossRef] [PubMed]

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. A. M. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials29(12), 1912–1919 (2008).
[CrossRef] [PubMed]

D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express16(7), 4376–4393 (2008).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal Optical Coherence Tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

2007 (6)

T. Akkin, C. Joo, and J. F. de Boer, “Depth-resolved measurement of transient structural changes during action potential propagation,” Biophys. J.93(4), 1347–1353 (2007).
[CrossRef] [PubMed]

H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni, “Renal clearance of quantum dots,” Nat. Biotechnol.25(10), 1165–1170 (2007).
[CrossRef] [PubMed]

A. M. Gobin, M. H. Lee, N. J. Halas, W. D. James, R. A. Drezek, and J. L. West, “Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy,” Nano Lett.7(7), 1929–1934 (2007).
[CrossRef] [PubMed]

A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys.102(6), 064701 (2007).
[CrossRef]

A. K. Oyelere, P. C. Chen, X. H. Huang, I. H. El-Sayed, and M. A. El-Sayed, “Peptide-conjugated gold nanorods for nuclear targeting,” Bioconjug. Chem.18(5), 1490–1497 (2007).
[CrossRef] [PubMed]

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, “Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods,” Nano Lett.7(4), 941–945 (2007).
[CrossRef] [PubMed]

2006 (3)

J. F. Hainfeld, D. N. Slatkin, T. M. Focella, and H. M. Smilowitz, “Gold nanoparticles: a new X-ray contrast agent,” Br. J. Radiol.79(939), 248–253 (2006).
[CrossRef] [PubMed]

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2005 (1)

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2004 (1)

M. D. Wojtkowski, T. H. Ko, J. G. Fujimoto, T. Bajraszewski, I. Gorczynska, P. Targowski, A. Kowalczyk, J. S. Schuman, and J. S. Duker, “Ultrahigh speed, ultrahigh resolution optical coherence tomography using spectral domain detection,” Invest. Ophthalmol. Vis. Sci.45, U50 (2004).

2003 (1)

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1998 (1)

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R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
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Agarwal, A.

A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys.102(6), 064701 (2007).
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G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas,” Cancer Res.69(9), 3892–3900 (2009).
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T. Akkin, C. Joo, and J. F. de Boer, “Depth-resolved measurement of transient structural changes during action potential propagation,” Biophys. J.93(4), 1347–1353 (2007).
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S. K. Libutti, G. F. Paciotti, A. A. Byrnes, H. R. Alexander, W. E. Gannon, M. Walker, G. D. Seidel, N. Yuldasheva, and L. Tamarkin, “Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine,” Clin. Cancer Res.16(24), 6139–6149 (2010).
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X. M. Qian, X. H. Peng, D. O. Ansari, Q. Yin-Goen, G. Z. Chen, D. M. Shin, L. Yang, A. N. Young, M. D. Wang, and S. M. Nie, “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags,” Nat. Biotechnol.26(1), 83–90 (2008).
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Ashkenazi, S.

A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys.102(6), 064701 (2007).
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M. D. Wojtkowski, T. H. Ko, J. G. Fujimoto, T. Bajraszewski, I. Gorczynska, P. Targowski, A. Kowalczyk, J. S. Schuman, and J. S. Duker, “Ultrahigh speed, ultrahigh resolution optical coherence tomography using spectral domain detection,” Invest. Ophthalmol. Vis. Sci.45, U50 (2004).

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G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas,” Cancer Res.69(9), 3892–3900 (2009).
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Bartlett, L. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni, “Renal clearance of quantum dots,” Nat. Biotechnol.25(10), 1165–1170 (2007).
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S. W. Jones, R. A. Roberts, G. R. Robbins, J. L. Perry, M. P. Kai, K. Chen, T. Bo, M. E. Napier, J. P. Y. Ting, J. M. Desimone, and J. E. Bear, “Nanoparticle clearance is governed by Th1/Th2 immunity and strain background,” J. Clin. Invest.123(7), 3061–3073 (2013).
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N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, “Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods,” Nano Lett.7(4), 941–945 (2007).
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Bhatia, S. N.

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas,” Cancer Res.69(9), 3892–3900 (2009).
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S. W. Jones, R. A. Roberts, G. R. Robbins, J. L. Perry, M. P. Kai, K. Chen, T. Bo, M. E. Napier, J. P. Y. Ting, J. M. Desimone, and J. E. Bear, “Nanoparticle clearance is governed by Th1/Th2 immunity and strain background,” J. Clin. Invest.123(7), 3061–3073 (2013).
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Boppart, S. A.

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
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A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
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B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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Burger, M. C.

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. A. M. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials29(12), 1912–1919 (2008).
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S. K. Libutti, G. F. Paciotti, A. A. Byrnes, H. R. Alexander, W. E. Gannon, M. Walker, G. D. Seidel, N. Yuldasheva, and L. Tamarkin, “Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine,” Clin. Cancer Res.16(24), 6139–6149 (2010).
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Cable, A.

Chan, W. C. W.

S. D. Perrault, C. Walkey, T. Jennings, H. C. Fischer, and W. C. W. Chan, “Mediating Tumor Targeting Efficiency of Nanoparticles Through Design,” Nano Lett.9(5), 1909–1915 (2009).
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Chaney, E. J.

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
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Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, G. Z.

X. M. Qian, X. H. Peng, D. O. Ansari, Q. Yin-Goen, G. Z. Chen, D. M. Shin, L. Yang, A. N. Young, M. D. Wang, and S. M. Nie, “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags,” Nat. Biotechnol.26(1), 83–90 (2008).
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Chen, K.

S. W. Jones, R. A. Roberts, G. R. Robbins, J. L. Perry, M. P. Kai, K. Chen, T. Bo, M. E. Napier, J. P. Y. Ting, J. M. Desimone, and J. E. Bear, “Nanoparticle clearance is governed by Th1/Th2 immunity and strain background,” J. Clin. Invest.123(7), 3061–3073 (2013).
[CrossRef] [PubMed]

Chen, P. C.

A. K. Oyelere, P. C. Chen, X. H. Huang, I. H. El-Sayed, and M. A. El-Sayed, “Peptide-conjugated gold nanorods for nuclear targeting,” Bioconjug. Chem.18(5), 1490–1497 (2007).
[CrossRef] [PubMed]

Chen, Y. S.

Y. S. Chen, W. Frey, S. Kim, P. Kruizinga, K. Homan, and S. Emelianov, “Silica-Coated Gold Nanorods as Photoacoustic Signal Nanoamplifiers,” Nano Lett.11(2), 348–354 (2011).
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Chen, Z. P.

Cheng, J. X.

L. Tong, Q. S. Wei, A. Wei, and J. X. Cheng, “Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects,” Photochem. Photobiol.85(1), 21–32 (2009).
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Chilkoti, A.

A. A. Manzoor, L. H. Lindner, C. D. Landon, J. Y. Park, A. J. Simnick, M. R. Dreher, S. Das, G. Hanna, W. Park, A. Chilkoti, G. A. Koning, T. L. M. ten Hagen, D. Needham, and M. W. Dewhirst, “Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors,” Cancer Res.72(21), 5566–5575 (2012).
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M. R. Dreher, W. G. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst.98(5), 335–344 (2006).
[CrossRef] [PubMed]

Chiu, S. J.

Choi, H. S.

H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni, “Renal clearance of quantum dots,” Nat. Biotechnol.25(10), 1165–1170 (2007).
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Coleman, C. L.

J. A. Schwartz, A. M. Shetty, R. E. Price, R. J. Stafford, J. C. Wang, R. K. Uthamanthil, K. Pham, R. J. McNichols, C. L. Coleman, and J. D. Payne, “Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model,” Cancer Res.69(4), 1659–1667 (2009).
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Colvin, D. C.

Crow, M. J.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal Optical Coherence Tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
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Das, S.

A. A. Manzoor, L. H. Lindner, C. D. Landon, J. Y. Park, A. J. Simnick, M. R. Dreher, S. Das, G. Hanna, W. Park, A. Chilkoti, G. A. Koning, T. L. M. ten Hagen, D. Needham, and M. W. Dewhirst, “Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors,” Cancer Res.72(21), 5566–5575 (2012).
[CrossRef] [PubMed]

Das, S. K.

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas,” Cancer Res.69(9), 3892–3900 (2009).
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Davis, G.

C. L. Zavaleta, B. R. Smith, I. Walton, W. Doering, G. Davis, B. Shojaei, M. J. Natan, and S. S. Gambhir, “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.106(32), 13511–13516 (2009).
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Day, K. C.

A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys.102(6), 064701 (2007).
[CrossRef]

Day, M.

A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys.102(6), 064701 (2007).
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de Boer, J. F.

T. Akkin, C. Joo, and J. F. de Boer, “Depth-resolved measurement of transient structural changes during action potential propagation,” Biophys. J.93(4), 1347–1353 (2007).
[CrossRef] [PubMed]

De Jong, W. H.

W. H. De Jong, W. I. Hagens, P. Krystek, M. C. Burger, A. J. A. M. Sips, and R. E. Geertsma, “Particle size-dependent organ distribution of gold nanoparticles after intravenous administration,” Biomaterials29(12), 1912–1919 (2008).
[CrossRef] [PubMed]

Desimone, J. M.

S. W. Jones, R. A. Roberts, G. R. Robbins, J. L. Perry, M. P. Kai, K. Chen, T. Bo, M. E. Napier, J. P. Y. Ting, J. M. Desimone, and J. E. Bear, “Nanoparticle clearance is governed by Th1/Th2 immunity and strain background,” J. Clin. Invest.123(7), 3061–3073 (2013).
[CrossRef] [PubMed]

Dewhirst, M. W.

A. A. Manzoor, L. H. Lindner, C. D. Landon, J. Y. Park, A. J. Simnick, M. R. Dreher, S. Das, G. Hanna, W. Park, A. Chilkoti, G. A. Koning, T. L. M. ten Hagen, D. Needham, and M. W. Dewhirst, “Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors,” Cancer Res.72(21), 5566–5575 (2012).
[CrossRef] [PubMed]

M. R. Dreher, W. G. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst.98(5), 335–344 (2006).
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Diagaradjane, P.

J. Park, A. Estrada, J. A. Schwartz, P. Diagaradjane, S. Krishnan, A. K. Dunn, and J. W. Tunnell, “Intra-Organ Biodistribution of Gold Nanoparticles Using Intrinsic Two-photon Induced Photoluminescence,” Lasers Surg. Med.42(7), 630–639 (2010).
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Doering, W.

C. L. Zavaleta, B. R. Smith, I. Walton, W. Doering, G. Davis, B. Shojaei, M. J. Natan, and S. S. Gambhir, “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.106(32), 13511–13516 (2009).
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Dreher, M. R.

A. A. Manzoor, L. H. Lindner, C. D. Landon, J. Y. Park, A. J. Simnick, M. R. Dreher, S. Das, G. Hanna, W. Park, A. Chilkoti, G. A. Koning, T. L. M. ten Hagen, D. Needham, and M. W. Dewhirst, “Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors,” Cancer Res.72(21), 5566–5575 (2012).
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M. R. Dreher, W. G. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst.98(5), 335–344 (2006).
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A. M. Gobin, M. H. Lee, N. J. Halas, W. D. James, R. A. Drezek, and J. L. West, “Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy,” Nano Lett.7(7), 1929–1934 (2007).
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Duker, J. S.

M. D. Wojtkowski, T. H. Ko, J. G. Fujimoto, T. Bajraszewski, I. Gorczynska, P. Targowski, A. Kowalczyk, J. S. Schuman, and J. S. Duker, “Ultrahigh speed, ultrahigh resolution optical coherence tomography using spectral domain detection,” Invest. Ophthalmol. Vis. Sci.45, U50 (2004).

Dunn, A. K.

J. Park, A. Estrada, J. A. Schwartz, P. Diagaradjane, S. Krishnan, A. K. Dunn, and J. W. Tunnell, “Intra-Organ Biodistribution of Gold Nanoparticles Using Intrinsic Two-photon Induced Photoluminescence,” Lasers Surg. Med.42(7), 630–639 (2010).
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Durr, N. J.

N. J. Durr, T. Larson, D. K. Smith, B. A. Korgel, K. Sokolov, and A. Ben-Yakar, “Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods,” Nano Lett.7(4), 941–945 (2007).
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Duvall, C. L.

El-Sayed, I. H.

A. K. Oyelere, P. C. Chen, X. H. Huang, I. H. El-Sayed, and M. A. El-Sayed, “Peptide-conjugated gold nanorods for nuclear targeting,” Bioconjug. Chem.18(5), 1490–1497 (2007).
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El-Sayed, M. A.

A. K. Oyelere, P. C. Chen, X. H. Huang, I. H. El-Sayed, and M. A. El-Sayed, “Peptide-conjugated gold nanorods for nuclear targeting,” Bioconjug. Chem.18(5), 1490–1497 (2007).
[CrossRef] [PubMed]

Emelianov, S.

Y. S. Chen, W. Frey, S. Kim, P. Kruizinga, K. Homan, and S. Emelianov, “Silica-Coated Gold Nanorods as Photoacoustic Signal Nanoamplifiers,” Nano Lett.11(2), 348–354 (2011).
[CrossRef] [PubMed]

Estrada, A.

J. Park, A. Estrada, J. A. Schwartz, P. Diagaradjane, S. Krishnan, A. K. Dunn, and J. W. Tunnell, “Intra-Organ Biodistribution of Gold Nanoparticles Using Intrinsic Two-photon Induced Photoluminescence,” Lasers Surg. Med.42(7), 630–639 (2010).
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Estrada, R.

Fang, J.

J. Fang, H. Nakamura, and H. Maeda, “The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect,” Adv. Drug Deliv. Rev.63(3), 136–151 (2011).
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A. K. Iyer, G. Khaled, J. Fang, and H. Maeda, “Exploiting the enhanced permeability and retention effect for tumor targeting,” Drug Discov. Today11(17-18), 812–818 (2006).
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Farsiu, S.

Feldman, M. D.

Fischer, H. C.

S. D. Perrault, C. Walkey, T. Jennings, H. C. Fischer, and W. C. W. Chan, “Mediating Tumor Targeting Efficiency of Nanoparticles Through Design,” Nano Lett.9(5), 1909–1915 (2009).
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Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science254(5035), 1178–1181 (1991).
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Focella, T. M.

J. F. Hainfeld, D. N. Slatkin, T. M. Focella, and H. M. Smilowitz, “Gold nanoparticles: a new X-ray contrast agent,” Br. J. Radiol.79(939), 248–253 (2006).
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Frangioni, J. V.

H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni, “Renal clearance of quantum dots,” Nat. Biotechnol.25(10), 1165–1170 (2007).
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Frey, W.

Y. S. Chen, W. Frey, S. Kim, P. Kruizinga, K. Homan, and S. Emelianov, “Silica-Coated Gold Nanorods as Photoacoustic Signal Nanoamplifiers,” Nano Lett.11(2), 348–354 (2011).
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D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express16(7), 4376–4393 (2008).
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M. D. Wojtkowski, T. H. Ko, J. G. Fujimoto, T. Bajraszewski, I. Gorczynska, P. Targowski, A. Kowalczyk, J. S. Schuman, and J. S. Duker, “Ultrahigh speed, ultrahigh resolution optical coherence tomography using spectral domain detection,” Invest. Ophthalmol. Vis. Sci.45, U50 (2004).

J. G. Fujimoto, “Optical coherence tomography for ultrahigh resolution in vivo imaging,” Nat. Biotechnol.21(11), 1361–1367 (2003).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science254(5035), 1178–1181 (1991).
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Fukumura, D.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
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Gambhir, S. S.

A. S. Thakor, J. Jokerst, C. Zavaleta, T. F. Massoud, and S. S. Gambhir, “Gold Nanoparticles: A Revival in Precious Metal Administration to Patients,” Nano Lett.11(10), 4029–4036 (2011).
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C. L. Zavaleta, B. R. Smith, I. Walton, W. Doering, G. Davis, B. Shojaei, M. J. Natan, and S. S. Gambhir, “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.106(32), 13511–13516 (2009).
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G. Y. Guan, R. Reif, Z. H. Huang, and R. K. K. Wang, “Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography,” J. Biomed. Opt.16(12), 126003 (2011).
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M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal Optical Coherence Tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
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A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
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L. Tong, Q. S. Wei, A. Wei, and J. X. Cheng, “Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects,” Photochem. Photobiol.85(1), 21–32 (2009).
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L. Tong, Q. S. Wei, A. Wei, and J. X. Cheng, “Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects,” Photochem. Photobiol.85(1), 21–32 (2009).
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X. M. Qian, X. H. Peng, D. O. Ansari, Q. Yin-Goen, G. Z. Chen, D. M. Shin, L. Yang, A. N. Young, M. D. Wang, and S. M. Nie, “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags,” Nat. Biotechnol.26(1), 83–90 (2008).
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X. M. Qian, X. H. Peng, D. O. Ansari, Q. Yin-Goen, G. Z. Chen, D. M. Shin, L. Yang, A. N. Young, M. D. Wang, and S. M. Nie, “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags,” Nat. Biotechnol.26(1), 83–90 (2008).
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S. K. Libutti, G. F. Paciotti, A. A. Byrnes, H. R. Alexander, W. E. Gannon, M. Walker, G. D. Seidel, N. Yuldasheva, and L. Tamarkin, “Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine,” Clin. Cancer Res.16(24), 6139–6149 (2010).
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A. S. Thakor, J. Jokerst, C. Zavaleta, T. F. Massoud, and S. S. Gambhir, “Gold Nanoparticles: A Revival in Precious Metal Administration to Patients,” Nano Lett.11(10), 4029–4036 (2011).
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C. L. Zavaleta, B. R. Smith, I. Walton, W. Doering, G. Davis, B. Shojaei, M. J. Natan, and S. S. Gambhir, “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.106(32), 13511–13516 (2009).
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Y. Jung, R. Reif, Y. G. Zeng, and R. K. Wang, “Three-Dimensional High-Resolution Imaging of Gold Nanorods Uptake in Sentinel Lymph Nodes,” Nano Lett.11(7), 2938–2943 (2011).
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H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni, “Renal clearance of quantum dots,” Nat. Biotechnol.25(10), 1165–1170 (2007).
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Biomaterials (1)

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J. A. Schwartz, A. M. Shetty, R. E. Price, R. J. Stafford, J. C. Wang, R. K. Uthamanthil, K. Pham, R. J. McNichols, C. L. Coleman, and J. D. Payne, “Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model,” Cancer Res.69(4), 1659–1667 (2009).
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Invest. Ophthalmol. Vis. Sci. (1)

M. D. Wojtkowski, T. H. Ko, J. G. Fujimoto, T. Bajraszewski, I. Gorczynska, P. Targowski, A. Kowalczyk, J. S. Schuman, and J. S. Duker, “Ultrahigh speed, ultrahigh resolution optical coherence tomography using spectral domain detection,” Invest. Ophthalmol. Vis. Sci.45, U50 (2004).

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A. Agarwal, S. W. Huang, M. O’Donnell, K. C. Day, M. Day, N. Kotov, and S. Ashkenazi, “Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging,” J. Appl. Phys.102(6), 064701 (2007).
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G. Y. Guan, R. Reif, Z. H. Huang, and R. K. K. Wang, “Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography,” J. Biomed. Opt.16(12), 126003 (2011).
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S. W. Jones, R. A. Roberts, G. R. Robbins, J. L. Perry, M. P. Kai, K. Chen, T. Bo, M. E. Napier, J. P. Y. Ting, J. M. Desimone, and J. E. Bear, “Nanoparticle clearance is governed by Th1/Th2 immunity and strain background,” J. Clin. Invest.123(7), 3061–3073 (2013).
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A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
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J. Natl. Cancer Inst. (1)

M. R. Dreher, W. G. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, and A. Chilkoti, “Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers,” J. Natl. Cancer Inst.98(5), 335–344 (2006).
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A. M. Gobin, M. H. Lee, N. J. Halas, W. D. James, R. A. Drezek, and J. L. West, “Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy,” Nano Lett.7(7), 1929–1934 (2007).
[CrossRef] [PubMed]

A. S. Thakor, J. Jokerst, C. Zavaleta, T. F. Massoud, and S. S. Gambhir, “Gold Nanoparticles: A Revival in Precious Metal Administration to Patients,” Nano Lett.11(10), 4029–4036 (2011).
[CrossRef] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal Optical Coherence Tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett.8(10), 3461–3467 (2008).
[CrossRef] [PubMed]

Y. Jung, R. Reif, Y. G. Zeng, and R. K. Wang, “Three-Dimensional High-Resolution Imaging of Gold Nanorods Uptake in Sentinel Lymph Nodes,” Nano Lett.11(7), 2938–2943 (2011).
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H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, and J. V. Frangioni, “Renal clearance of quantum dots,” Nat. Biotechnol.25(10), 1165–1170 (2007).
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J. G. Fujimoto, “Optical coherence tomography for ultrahigh resolution in vivo imaging,” Nat. Biotechnol.21(11), 1361–1367 (2003).
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X. M. Qian, X. H. Peng, D. O. Ansari, Q. Yin-Goen, G. Z. Chen, D. M. Shin, L. Yang, A. N. Young, M. D. Wang, and S. M. Nie, “In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags,” Nat. Biotechnol.26(1), 83–90 (2008).
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L. Tong, Q. S. Wei, A. Wei, and J. X. Cheng, “Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects,” Photochem. Photobiol.85(1), 21–32 (2009).
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C. L. Zavaleta, B. R. Smith, I. Walton, W. Doering, G. Davis, B. Shojaei, M. J. Natan, and S. S. Gambhir, “Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy,” Proc. Natl. Acad. Sci. U.S.A.106(32), 13511–13516 (2009).
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