Abstract

Lack of better understanding of nanoparticles targeted delivery into cancer cells calls for advanced optical microscopy methodologies. Here we present a development of fluorescence microspectroscopy (spectral imaging) based on a white light spinning disk confocal microscope with emission wavelength selection by a liquid crystal tunable filter. Spectral contrasting of images was used to localize polymer nanoparticles and cell membranes labeled with fluorophores that have substantially overlapping spectra. In addition, fluorescence microspectroscopy enabled spatially-resolved detection of small but significant effects of local molecular environment on the properties of environment-sensitive fluorescent probe. The observed spectral shift suggests that the delivery of suitably composed cancerostatic alkylphospholipid nanoparticles into living cancer cells might rely on the fusion with plasma cell membrane.

© 2011 OSA

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]

2011 (6)

K. Loomis, K. McNeeley, and R. V. Bellamkonda, “Nanoparticles with targeting, triggered release, and imaging functionality for cancer applications,” Soft Matter 7(3), 839–856 (2011).
[CrossRef]

V. Torchilin, “Tumor delivery of macromolecular drugs based on the EPR effect,” Adv. Drug Deliv. Rev. 63(3), 131–135 (2011).
[CrossRef] [PubMed]

G. Zacharakis, R. Favicchio, M. Simantiraki, and J. Ripoll, “Spectroscopic detection improves multi-color quantification in fluorescence tomography,” Biomed. Opt. Express 2(3), 431–439 (2011).
[PubMed]

S. Pajk, M. Garvas, J. Štrancar, and S. Pečar, “Nitroxide-fluorophore double probes: a potential tool for studying membrane heterogeneity by ESR and fluorescence,” Org. Biomol. Chem. 9(11), 4150–4159 (2011).
[CrossRef] [PubMed]

A. Esposito, A. N. Bader, S. C. Schlachter, D. J. van den Heuvel, G. S. Schierle, A. R. Venkitaraman, C. F. Kaminski, and H. C. Gerritsen, “Design and application of a confocal microscope for spectrally resolved anisotropy imaging,” Opt. Express 19(3), 2546–2555 (2011).
[CrossRef] [PubMed]

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

2010 (4)

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

J. M. Lerner, N. Gat, and E. Wachman, “Approaches to spectral imaging hardware,” Curr. Protoc. Cytom. 53, 12.20.1–12.20.40 (2010).
[PubMed]

M. Baker, “Laser tricks without labels,” Nat. Methods 7(4), 261–266 (2010).
[CrossRef] [PubMed]

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

2009 (1)

A. P. Demchenko, Y. Mély, G. Duportail, and A. S. Klymchenko, “Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes,” Biophys. J. 96(9), 3461–3470 (2009).
[CrossRef] [PubMed]

2008 (2)

M. Hintersteiner and M. Auer, “Single-bead, single-molecule, single-cell fluorescence: technologies for drug screening and target validation,” Ann. N. Y. Acad. Sci. 1130(1), 1–11 (2008).
[CrossRef] [PubMed]

T. Koklič, R. Zeisig, and M. Šentjurc, “Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration,” Biochim. Biophys. Acta 1778(12), 2682–2689 (2008).
[CrossRef] [PubMed]

2007 (4)

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

S. J. Woltman, G. D. Jay, and G. P. Crawford, “Liquid-crystal materials find a new order in biomedical applications,” Nat. Mater. 6(12), 929–938 (2007).
[CrossRef] [PubMed]

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

2006 (3)

R. M. Levenson and J. R. Mansfield, “Multispectral imaging in biology and medicine: slices of life,” Cytometry A 69A(8), 748–758 (2006).
[CrossRef] [PubMed]

Y. Garini, I. T. Young, and G. McNamara, “Spectral imaging: principles and applications,” Cytometry A 69A(8), 735–747 (2006).
[CrossRef] [PubMed]

M. Eisenstein, “Something to see,” Nature 443(7114), 1017–1021 (2006).
[PubMed]

2005 (5)

J.-A. Conchello and J. W. Lichtman, “Optical sectioning microscopy,” Nat. Methods 2(12), 920–931 (2005).
[CrossRef] [PubMed]

C. Oberle, U. Massing, and H. F. Krug, “On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells,” Biol. Chem. 386(3), 237–245 (2005).
[CrossRef] [PubMed]

R. Gräf, J. Rietdorf, and T. Zimmermann, “Live cell spinning disk microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 57–75 (2005).
[PubMed]

T. Zimmermann, “Spectral imaging and linear unmixing in light microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 245–265 (2005).
[PubMed]

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

2003 (1)

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

2002 (1)

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[CrossRef] [PubMed]

2001 (2)

R. Lansford, G. Bearman, and S. E. Fraser, “Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy,” J. Biomed. Opt. 6(3), 311–318 (2001).
[CrossRef] [PubMed]

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

2000 (1)

L. A. Bagatolli and E. Gratton, “A correlation between lipid domain shape and binary phospholipid mixture composition in free standing bilayers: A two-photon fluorescence microscopy study,” Biophys. J. 79(1), 434–447 (2000).
[CrossRef] [PubMed]

1998 (1)

R. Zeisig, D. Arndt, R. Stahn, and I. Fichtner, “Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid,” Biochim. Biophys. Acta 1414(1-2), 238–248 (1998).
[CrossRef] [PubMed]

1996 (1)

T. Schmidt, G. J. Schütz, W. Baumgartner, H. J. Gruber, and H. Schindler, “Imaging of single molecule diffusion,” Proc. Natl. Acad. Sci. U.S.A. 93(7), 2926–2929 (1996).
[CrossRef] [PubMed]

1994 (1)

Arndt, D.

R. Zeisig, D. Arndt, R. Stahn, and I. Fichtner, “Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid,” Biochim. Biophys. Acta 1414(1-2), 238–248 (1998).
[CrossRef] [PubMed]

Auer, M.

M. Hintersteiner and M. Auer, “Single-bead, single-molecule, single-cell fluorescence: technologies for drug screening and target validation,” Ann. N. Y. Acad. Sci. 1130(1), 1–11 (2008).
[CrossRef] [PubMed]

Bader, A. N.

Bagatolli, L. A.

L. A. Bagatolli and E. Gratton, “A correlation between lipid domain shape and binary phospholipid mixture composition in free standing bilayers: A two-photon fluorescence microscopy study,” Biophys. J. 79(1), 434–447 (2000).
[CrossRef] [PubMed]

Baker, M.

M. Baker, “Laser tricks without labels,” Nat. Methods 7(4), 261–266 (2010).
[CrossRef] [PubMed]

Bartucci, R.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Baumgartner, W.

T. Schmidt, G. J. Schütz, W. Baumgartner, H. J. Gruber, and H. Schindler, “Imaging of single molecule diffusion,” Proc. Natl. Acad. Sci. U.S.A. 93(7), 2926–2929 (1996).
[CrossRef] [PubMed]

Bearman, G.

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

R. Lansford, G. Bearman, and S. E. Fraser, “Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy,” J. Biomed. Opt. 6(3), 311–318 (2001).
[CrossRef] [PubMed]

Bellamkonda, R. V.

K. Loomis, K. McNeeley, and R. V. Bellamkonda, “Nanoparticles with targeting, triggered release, and imaging functionality for cancer applications,” Soft Matter 7(3), 839–856 (2011).
[CrossRef]

Borst, J. W.

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

Cho, B. R.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Choo, H.-J.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Chourpa, I.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Chua, M.

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

Clements, I.

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

Cohen-Jonathan, S.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Conchello, J.-A.

J.-A. Conchello and J. W. Lichtman, “Optical sectioning microscopy,” Nat. Methods 2(12), 920–931 (2005).
[CrossRef] [PubMed]

Crawford, G. P.

S. J. Woltman, G. D. Jay, and G. P. Crawford, “Liquid-crystal materials find a new order in biomedical applications,” Nat. Mater. 6(12), 929–938 (2007).
[CrossRef] [PubMed]

de Almeida, R. F. M.

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

Demchenko, A. P.

A. P. Demchenko, Y. Mély, G. Duportail, and A. S. Klymchenko, “Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes,” Biophys. J. 96(9), 3461–3470 (2009).
[CrossRef] [PubMed]

Dickinson, M. E.

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

Dubois, P.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Duportail, G.

A. P. Demchenko, Y. Mély, G. Duportail, and A. S. Klymchenko, “Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes,” Biophys. J. 96(9), 3461–3470 (2009).
[CrossRef] [PubMed]

Dzuba, S. A.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Eisenstein, M.

M. Eisenstein, “Something to see,” Nature 443(7114), 1017–1021 (2006).
[PubMed]

Erilov, D. A.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Esposito, A.

Favicchio, R.

Fedorov, A.

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

Fichtner, I.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

R. Zeisig, D. Arndt, R. Stahn, and I. Fichtner, “Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid,” Biochim. Biophys. Acta 1414(1-2), 238–248 (1998).
[CrossRef] [PubMed]

Fischer, R.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

Fraser, S. E.

R. Lansford, G. Bearman, and S. E. Fraser, “Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy,” J. Biomed. Opt. 6(3), 311–318 (2001).
[CrossRef] [PubMed]

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

Garini, Y.

Y. Garini, I. T. Young, and G. McNamara, “Spectral imaging: principles and applications,” Cytometry A 69A(8), 735–747 (2006).
[CrossRef] [PubMed]

Garvas, M.

S. Pajk, M. Garvas, J. Štrancar, and S. Pečar, “Nitroxide-fluorophore double probes: a potential tool for studying membrane heterogeneity by ESR and fluorescence,” Org. Biomol. Chem. 9(11), 4150–4159 (2011).
[CrossRef] [PubMed]

Gat, N.

J. M. Lerner, N. Gat, and E. Wachman, “Approaches to spectral imaging hardware,” Curr. Protoc. Cytom. 53, 12.20.1–12.20.40 (2010).
[PubMed]

Gerritsen, H. C.

Gräf, R.

R. Gräf, J. Rietdorf, and T. Zimmermann, “Live cell spinning disk microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 57–75 (2005).
[PubMed]

Gratton, E.

L. A. Bagatolli and E. Gratton, “A correlation between lipid domain shape and binary phospholipid mixture composition in free standing bilayers: A two-photon fluorescence microscopy study,” Biophys. J. 79(1), 434–447 (2000).
[CrossRef] [PubMed]

Gruber, H. J.

T. Schmidt, G. J. Schütz, W. Baumgartner, H. J. Gruber, and H. Schindler, “Imaging of single molecule diffusion,” Proc. Natl. Acad. Sci. U.S.A. 93(7), 2926–2929 (1996).
[CrossRef] [PubMed]

Guzzi, R.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Haraguchi, T.

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[CrossRef] [PubMed]

Helm, M.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

Herve, K.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Hintersteiner, M.

M. Hintersteiner and M. Auer, “Single-bead, single-molecule, single-cell fluorescence: technologies for drug screening and target validation,” Ann. N. Y. Acad. Sci. 1130(1), 1–11 (2008).
[CrossRef] [PubMed]

Hiraoka, Y.

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[CrossRef] [PubMed]

Hirsch, M.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

Hoyt, C. C.

Järve, A.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

Jay, G. D.

S. J. Woltman, G. D. Jay, and G. P. Crawford, “Liquid-crystal materials find a new order in biomedical applications,” Nat. Mater. 6(12), 929–938 (2007).
[CrossRef] [PubMed]

Jeon, S.-J.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Joo, T.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Jung, S.-Y.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Kaminski, C. F.

Kim, C. H.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Kim, H. M.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Kim, I.-H.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

Klymchenko, A. S.

A. P. Demchenko, Y. Mély, G. Duportail, and A. S. Klymchenko, “Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes,” Biophys. J. 96(9), 3461–3470 (2009).
[CrossRef] [PubMed]

Ko, Y.-G.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Koklic, T.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

T. Koklič, R. Zeisig, and M. Šentjurc, “Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration,” Biochim. Biophys. Acta 1778(12), 2682–2689 (2008).
[CrossRef] [PubMed]

Krug, H. F.

C. Oberle, U. Massing, and H. F. Krug, “On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells,” Biol. Chem. 386(3), 237–245 (2005).
[CrossRef] [PubMed]

Lansford, R.

R. Lansford, G. Bearman, and S. E. Fraser, “Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy,” J. Biomed. Opt. 6(3), 311–318 (2001).
[CrossRef] [PubMed]

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

Lemm, M.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

Lerner, J. M.

J. M. Lerner, N. Gat, and E. Wachman, “Approaches to spectral imaging hardware,” Curr. Protoc. Cytom. 53, 12.20.1–12.20.40 (2010).
[PubMed]

Levenson, R. M.

R. M. Levenson and J. R. Mansfield, “Multispectral imaging in biology and medicine: slices of life,” Cytometry A 69A(8), 748–758 (2006).
[CrossRef] [PubMed]

Lichtman, J. W.

J.-A. Conchello and J. W. Lichtman, “Optical sectioning microscopy,” Nat. Methods 2(12), 920–931 (2005).
[CrossRef] [PubMed]

Linassier, C.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Loomis, K.

K. Loomis, K. McNeeley, and R. V. Bellamkonda, “Nanoparticles with targeting, triggered release, and imaging functionality for cancer applications,” Soft Matter 7(3), 839–856 (2011).
[CrossRef]

Mansfield, J. R.

R. M. Levenson and J. R. Mansfield, “Multispectral imaging in biology and medicine: slices of life,” Cytometry A 69A(8), 748–758 (2006).
[CrossRef] [PubMed]

Marsh, D.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Maryasov, A. G.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Massing, U.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

C. Oberle, U. Massing, and H. F. Krug, “On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells,” Biol. Chem. 386(3), 237–245 (2005).
[CrossRef] [PubMed]

McNamara, G.

Y. Garini, I. T. Young, and G. McNamara, “Spectral imaging: principles and applications,” Cytometry A 69A(8), 735–747 (2006).
[CrossRef] [PubMed]

McNeeley, K.

K. Loomis, K. McNeeley, and R. V. Bellamkonda, “Nanoparticles with targeting, triggered release, and imaging functionality for cancer applications,” Soft Matter 7(3), 839–856 (2011).
[CrossRef]

Mély, Y.

A. P. Demchenko, Y. Mély, G. Duportail, and A. S. Klymchenko, “Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes,” Biophys. J. 96(9), 3461–3470 (2009).
[CrossRef] [PubMed]

Morris, H. R.

Munnier, E.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Oberle, C.

C. Oberle, U. Massing, and H. F. Krug, “On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells,” Biol. Chem. 386(3), 237–245 (2005).
[CrossRef] [PubMed]

Orthmann, A.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

Pajk, S.

S. Pajk, M. Garvas, J. Štrancar, and S. Pečar, “Nitroxide-fluorophore double probes: a potential tool for studying membrane heterogeneity by ESR and fluorescence,” Org. Biomol. Chem. 9(11), 4150–4159 (2011).
[CrossRef] [PubMed]

Park, W.-H.

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Pecar, S.

S. Pajk, M. Garvas, J. Štrancar, and S. Pečar, “Nitroxide-fluorophore double probes: a potential tool for studying membrane heterogeneity by ESR and fluorescence,” Org. Biomol. Chem. 9(11), 4150–4159 (2011).
[CrossRef] [PubMed]

Pepperkok, R.

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

Prieto, M.

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

Rietdorf, J.

R. Gräf, J. Rietdorf, and T. Zimmermann, “Live cell spinning disk microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 57–75 (2005).
[PubMed]

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

Rigby, P.

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

Ripoll, J.

Rohr, K.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

Salmon, W.

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

Schierle, G. S.

Schindler, H.

T. Schmidt, G. J. Schütz, W. Baumgartner, H. J. Gruber, and H. Schindler, “Imaging of single molecule diffusion,” Proc. Natl. Acad. Sci. U.S.A. 93(7), 2926–2929 (1996).
[CrossRef] [PubMed]

Schlachter, S. C.

Schmidt, T.

T. Schmidt, G. J. Schütz, W. Baumgartner, H. J. Gruber, and H. Schindler, “Imaging of single molecule diffusion,” Proc. Natl. Acad. Sci. U.S.A. 93(7), 2926–2929 (1996).
[CrossRef] [PubMed]

Schütz, G. J.

T. Schmidt, G. J. Schütz, W. Baumgartner, H. J. Gruber, and H. Schindler, “Imaging of single molecule diffusion,” Proc. Natl. Acad. Sci. U.S.A. 93(7), 2926–2929 (1996).
[CrossRef] [PubMed]

Šentjurc, M.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

T. Koklič, R. Zeisig, and M. Šentjurc, “Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration,” Biochim. Biophys. Acta 1778(12), 2682–2689 (2008).
[CrossRef] [PubMed]

Shimi, T.

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[CrossRef] [PubMed]

Shubin, A. A.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Simantiraki, M.

Souce, M.

E. Munnier, S. Cohen-Jonathan, K. Herve, C. Linassier, M. Souce, P. Dubois, and I. Chourpa, “Doxorubicin delivered to MCF-7 cancer cells by superparamagnetic iron oxide nanoparticles: effects on subcellular distribution and cytotoxicity,” J. Nanopart. Res. 13(3), 959–971 (2011).
[CrossRef]

Sportelli, L.

D. A. Erilov, R. Bartucci, R. Guzzi, A. A. Shubin, A. G. Maryasov, D. Marsh, S. A. Dzuba, and L. Sportelli, “Water concentration profiles in membranes measured by ESEEM of spin-labeled lipids,” J. Phys. Chem. B 109(24), 12003–12013 (2005).
[CrossRef] [PubMed]

Stahn, R.

R. Zeisig, D. Arndt, R. Stahn, and I. Fichtner, “Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid,” Biochim. Biophys. Acta 1414(1-2), 238–248 (1998).
[CrossRef] [PubMed]

Štrancar, J.

S. Pajk, M. Garvas, J. Štrancar, and S. Pečar, “Nitroxide-fluorophore double probes: a potential tool for studying membrane heterogeneity by ESR and fluorescence,” Org. Biomol. Chem. 9(11), 4150–4159 (2011).
[CrossRef] [PubMed]

Tille, S.

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

Torchilin, V.

V. Torchilin, “Tumor delivery of macromolecular drugs based on the EPR effect,” Adv. Drug Deliv. Rev. 63(3), 131–135 (2011).
[CrossRef] [PubMed]

Treado, P. J.

Trendelenburg, M. F.

I.-H. Kim, A. Järve, M. Hirsch, R. Fischer, M. F. Trendelenburg, U. Massing, K. Rohr, and M. Helm, “FRET imaging of cells transfected with siRNA/liposome complexes,” Methods Mol. Biol. 606, 439–455 (2010).
[CrossRef] [PubMed]

van den Heuvel, D. J.

Venkitaraman, A. R.

Visser, A. J. W. G.

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

Wachman, E.

J. M. Lerner, N. Gat, and E. Wachman, “Approaches to spectral imaging hardware,” Curr. Protoc. Cytom. 53, 12.20.1–12.20.40 (2010).
[PubMed]

Wiesner, B.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

Woltman, S. J.

S. J. Woltman, G. D. Jay, and G. P. Crawford, “Liquid-crystal materials find a new order in biomedical applications,” Nat. Mater. 6(12), 929–938 (2007).
[CrossRef] [PubMed]

Young, I. T.

Y. Garini, I. T. Young, and G. McNamara, “Spectral imaging: principles and applications,” Cytometry A 69A(8), 735–747 (2006).
[CrossRef] [PubMed]

Zacharakis, G.

Zeisig, R.

A. Orthmann, R. Zeisig, T. Koklič, M. Šentjurc, B. Wiesner, M. Lemm, and I. Fichtner, “Impact of membrane properties on uptake and transcytosis of colloidal nanocarriers across an epithelial cell barrier model,” J. Pharm. Sci. 99(5), 2423–2433 (2010).
[PubMed]

T. Koklič, R. Zeisig, and M. Šentjurc, “Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration,” Biochim. Biophys. Acta 1778(12), 2682–2689 (2008).
[CrossRef] [PubMed]

R. Zeisig, D. Arndt, R. Stahn, and I. Fichtner, “Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid,” Biochim. Biophys. Acta 1414(1-2), 238–248 (1998).
[CrossRef] [PubMed]

Zimmermann, T.

R. Gräf, J. Rietdorf, and T. Zimmermann, “Live cell spinning disk microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 57–75 (2005).
[PubMed]

T. Zimmermann, “Spectral imaging and linear unmixing in light microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 245–265 (2005).
[PubMed]

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

Zucker, R. M.

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

Adv. Biochem. Eng. Biotechnol. (2)

R. Gräf, J. Rietdorf, and T. Zimmermann, “Live cell spinning disk microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 57–75 (2005).
[PubMed]

T. Zimmermann, “Spectral imaging and linear unmixing in light microscopy,” Adv. Biochem. Eng. Biotechnol. 95, 245–265 (2005).
[PubMed]

Adv. Drug Deliv. Rev. (1)

V. Torchilin, “Tumor delivery of macromolecular drugs based on the EPR effect,” Adv. Drug Deliv. Rev. 63(3), 131–135 (2011).
[CrossRef] [PubMed]

Ann. N. Y. Acad. Sci. (1)

M. Hintersteiner and M. Auer, “Single-bead, single-molecule, single-cell fluorescence: technologies for drug screening and target validation,” Ann. N. Y. Acad. Sci. 1130(1), 1–11 (2008).
[CrossRef] [PubMed]

Appl. Spectrosc. (1)

Biochim. Biophys. Acta (2)

T. Koklič, R. Zeisig, and M. Šentjurc, “Interaction of alkylphospholipid liposomes with MT-3 breast-cancer cells depends critically on cholesterol concentration,” Biochim. Biophys. Acta 1778(12), 2682–2689 (2008).
[CrossRef] [PubMed]

R. Zeisig, D. Arndt, R. Stahn, and I. Fichtner, “Physical properties and pharmacological activity in vitro and in vivo of optimised liposomes prepared from a new cancerostatic alkylphospholipid,” Biochim. Biophys. Acta 1414(1-2), 238–248 (1998).
[CrossRef] [PubMed]

Biol. Chem. (1)

C. Oberle, U. Massing, and H. F. Krug, “On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells,” Biol. Chem. 386(3), 237–245 (2005).
[CrossRef] [PubMed]

Biomed. Opt. Express (1)

Biophys. J. (3)

R. F. M. de Almeida, J. W. Borst, A. Fedorov, M. Prieto, and A. J. W. G. Visser, “Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by combining imaging and microscopic and macroscopic time-resolved fluorescence,” Biophys. J. 93(2), 539–553 (2007).
[CrossRef] [PubMed]

A. P. Demchenko, Y. Mély, G. Duportail, and A. S. Klymchenko, “Monitoring biophysical properties of lipid membranes by environment-sensitive fluorescent probes,” Biophys. J. 96(9), 3461–3470 (2009).
[CrossRef] [PubMed]

L. A. Bagatolli and E. Gratton, “A correlation between lipid domain shape and binary phospholipid mixture composition in free standing bilayers: A two-photon fluorescence microscopy study,” Biophys. J. 79(1), 434–447 (2000).
[CrossRef] [PubMed]

Biotechniques (1)

M. E. Dickinson, G. Bearman, S. Tille, R. Lansford, and S. E. Fraser, “Multi-spectral imaging and linear unmixing add a whole new dimension to laser scanning fluorescence microscopy,” Biotechniques 31(6), 1272–1278, 1274–1276, 1278 (2001).
[PubMed]

Cell Struct. Funct. (1)

Y. Hiraoka, T. Shimi, and T. Haraguchi, “Multispectral imaging fluorescence microscopy for living cells,” Cell Struct. Funct. 27(5), 367–374 (2002).
[CrossRef] [PubMed]

ChemBioChem (1)

H. M. Kim, H.-J. Choo, S.-Y. Jung, Y.-G. Ko, W.-H. Park, S.-J. Jeon, C. H. Kim, T. Joo, and B. R. Cho, “A two-photon fluorescent probe for lipid raft imaging: C-laurdan,” ChemBioChem 8(5), 553–559 (2007).
[CrossRef] [PubMed]

Curr. Protoc. Cytom. (1)

J. M. Lerner, N. Gat, and E. Wachman, “Approaches to spectral imaging hardware,” Curr. Protoc. Cytom. 53, 12.20.1–12.20.40 (2010).
[PubMed]

Cytometry A (3)

R. M. Levenson and J. R. Mansfield, “Multispectral imaging in biology and medicine: slices of life,” Cytometry A 69A(8), 748–758 (2006).
[CrossRef] [PubMed]

Y. Garini, I. T. Young, and G. McNamara, “Spectral imaging: principles and applications,” Cytometry A 69A(8), 735–747 (2006).
[CrossRef] [PubMed]

R. M. Zucker, P. Rigby, I. Clements, W. Salmon, and M. Chua, “Reliability of confocal microscopy spectral imaging systems: use of multispectral beads,” Cytometry A 71A(3), 174–189 (2007).
[CrossRef] [PubMed]

FEBS Lett. (1)

T. Zimmermann, J. Rietdorf, and R. Pepperkok, “Spectral imaging and its applications in live cell microscopy,” FEBS Lett. 546(1), 87–92 (2003).
[CrossRef] [PubMed]

J. Biomed. Opt. (1)

R. Lansford, G. Bearman, and S. E. Fraser, “Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy,” J. Biomed. Opt. 6(3), 311–318 (2001).
[CrossRef] [PubMed]

J. Nanopart. Res. (1)

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Figures (4)

Fig. 1
Fig. 1

A schematic presentation of the configuration of the experimental setup. The light coming from the spinning disk confocal module can be directed to the camera in two different paths by moving two mirrors (indicated by the double-headed arrows) in or out of the optical path. The first path (a) where the light goes through the LCTF represents the (confocal) fluorescence microspectroscopic mode while the second path (b) represents the conventional (confocal) fluorescence microscopy imaging mode.

Fig. 2
Fig. 2

Spectral contrasting of a microspectroscopic image. (a) Fluorescence microspectroscopic mode provides a stack of images obtained at different wavelength settings of the LCTF (a λ-stack of images) in FMS system. Different regions of interest can be selected from which (b) fluorescence emission spectra are extracted. The spectra are used in the color coding procedure to provide (c) a spectrally contrasted image, in this case the confocal image of equatorial optical slice through fluorescent beads. For details see text.

Fig. 3
Fig. 3

Interaction of polystyrene nanoparticles with living MCF-7 human breast cancer cells. Images of cells incubated in vitro with NBD-FA probe, i.e. a lipophilic NBD based fluorescent probe, and with (a) fluorescent 50 nm polymer nanoparticles imaged in wide-field mode or (b) imaged in confocal mode and with (c) 500 nm nanoparticles imaged in confocal mode. (a.1, b.1, c.1) Fluorescence intensity contrasted images. Fluorescent emission spectra of the nanoparticles and the lipophilic probe overlap, so it is not possible to determine the delivery efficiency of nanoparticles to the cancer cells from microscopic image, except for the aggregated nanoparticles indicated by arrows. (a.2, b.2, c.2) Spectrally contrasted images, which show the distribution of the NBD-FA probe (green/yellow) and fluorescein (violet/blue). The observed colors correspond to the measured (537 nm) and declared (shoulder at 515 nm) emission maximum values for membrane and nanoparticle probe, respectively.

Fig. 4
Fig. 4

Interaction of OPP lipid nanoparticles with living MCF-7 human breast cancer cells. Cells incubated in vitro with (a) 100 nm OPP5 LUV labeled with NBD-PC or with (b) labeled OPP15 LUV. (a.1-a.3, b.1-b.3) The time evolution of the intensity contrasted images of the cancer cells. (a.4, b.4) Color-coded images corresponding to the last image in the time line. Between the two color-coded images the histogram of the distribution of fitted spectrum peak positions (λmax) from the accordingly-colored squared regions in a.4 and b.4 are shown. The histogram confirms the significance of the observed small shifts in the λmax(hist) value.

Equations (1)

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h = 0.8   ( 1 ( λ m a x λ 1 λ 2 λ 1 ) 1.2 ) 1.3 , s = 1 , v = i 0.5 ,

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