The effect of co-delivery of paclitaxel and curcumin by transferrin-targeted PEG-PE-based mixed micelles on resistant ovarian cancer in 3-D spheroids and in vivo tumors

European Journal of Pharmaceutics and Biopharmaceutics

Volumn 88, Issue 2, 2014, Pages 539-550

  Sarisozen, Can ^a   Abouzeid, Abraham H ^a   Torchilin, Vladimir P ^a  

^a NORTHEASTERN UNIVERSITY   (United States)

Author keywords

Cancer cell spheroids; Co delivery; Curcumin; Micelles; Multi drug resistance; Paclitaxel; Transferrin

Indexed keywords

CURCUMIN; MACROGOL; PACLITAXEL; PHOSPHATIDYLETHANOLAMINE; TRANSFERRIN; TRANSFERRIN RECEPTOR; ANTINEOPLASTIC AGENT; MACROGOL DERIVATIVE; MICELLE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL CULTURE; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; DRUG ACCUMULATION; DRUG DELIVERY SYSTEM; DRUG PENETRATION; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IN VIVO STUDY; MICELLE; MONOLAYER CULTURE; MOUSE; NONHUMAN; OVARIAN CANCER CELL LINE; OVARY CANCER; PROTEIN EXPRESSION; TUMOR SPHEROID; CHEMISTRY; DRUG RESISTANCE; FEMALE; MULTICELLULAR SPHEROID; OVARY TUMOR; PATHOLOGY; TUMOR CELL LINE;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE, TUMOR; CURCUMIN; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MICELLES; OVARIAN NEOPLASMS; PACLITAXEL; PHOSPHATIDYLETHANOLAMINES; POLYETHYLENE GLYCOLS; SPHEROIDS, CELLULAR;

EID: 84908362289     PISSN: 09396411     EISSN: 18733441     Source Type: Journal    
DOI: 10.1016/j.ejpb.2014.07.001     Document Type: Article

References (110)

1. A.H. Abouzeid, N.R. Patel, C. Sarisozen, and V.P. Torchilin Transferrin-targeted polymeric micelles co-loaded with curcumin and paclitaxel: efficient killing of paclitaxel-resistant cancer cells Pharm. Res. 2014 10.1007/s11095-013-1295-x
2. M.E. Ackerman, D. Pawlowski, and K.D. Wittrup Effect of antigen turnover rate and expression level on antibody penetration into tumor spheroids Mol. Cancer Ther. 7 2008 2233 2240
3. B.B. Aggarwal Activation of transcription factor NF-kappaB is suppressed by curcumin (diferuloylmethane) J. Biol. Chem. 270 1995 24995 25000
4. A. Algeciras-Schimnich, E.M. Pietras, B.C. Barnhart, P. Legembre, S. Vijayan, S.L. Holbeck, and M.E. Peter Two CD95 tumor classes with different sensitivities to antitumor drugs Proc. Natl. Acad. Sci. USA 100 2003 11445 11450
5. P. Anand, H.B. Nair, B. Sung, A.B. Kunnumakkara, V.R. Yadav, R.R. Tekmal, and B.B. Aggarwal Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo Biochem. Pharmacol. 79 2010 330 338
6. P. Anand, C. Sundaram, S. Jhurani, A.B. Kunnumakkara, and B.B. Aggarwal Curcumin and cancer: an "old-age" disease with an "age-old" solution Cancer Lett. 267 2008 133 164
7. E.V. Batrakova, and A.V. Kabanov Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers J. Control. Release 130 2008 98 106
8. S.V. Bava, C.N. Sreekanth, A.K.T. Thulasidasan, N.P. Anto, V.T. Cheriyan, V.T. Puliyappadamba, S.G. Menon, S.D. Ravichandran, and R.J. Anto Akt is upstream and MAPKs are downstream of NF-kappa B in paclitaxel-induced survival signaling events, which are down-regulated by curcumin contributing to their synergism Int. J. Biochem. Cell Biol. 43 2011 331 341
9. A.L. Berrier, and K.M. Yamada Cell-matrix adhesion J. Cell. Physiol. 213 2007 565 573
10. K. Carver, X. Ming, and R.L. Juliano Multicellular tumor spheroids as a model for assessing delivery of oligonucleotides in three dimensions Mol. Ther. Nucl. Acids 3 2014 e153
11. T.T. Chang, and M. Hughes-Fulford Monolayer and spheroid culture of human liver hepatocellular carcinoma cell line cells demonstrate distinct global gene expression patterns and functional phenotypes Tissue Eng. Part A 15 2009 559 567
12. C.H. Choi, C.A. Alabi, P. Webster, and M.E. Davis Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles Proc. Natl. Acad. Sci. USA 107 2010 1235 1240
13. E. Cukierman, R. Pankov, D.R. Stevens, and K.M. Yamada Taking cell-matrix adhesions to the third dimension Science 294 2001 1708 1712
14. R.D. Dabholkar, R.M. Sawant, D.A. Mongayt, P.V. Devarajan, and V.P. Torchilin Polyethylene glycol-phosphatidylethanolamine conjugate (PEG-PE)-based mixed micelles: some properties, loading with paclitaxel, and modulation of P-glycoprotein-mediated efflux Int. J. Pharm. 315 2006 148 157
15. T.R. Daniels, E. Bernabeu, J.A. Rodriguez, S. Patel, M. Kozman, D.A. Chiappetta, E. Holler, J.Y. Ljubimova, G. Helguera, and M.L. Penichet The transferrin receptor and the targeted delivery of therapeutic agents against cancer Biochim. Biophys. Acta 1820 2012 291 317
16. T.R. Daniels, T. Delgado, G. Helguera, and M.L. Penichet The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells Clin. Immunol. 121 2006 159 176
17. A. Dicko, L.D. Mayer, and P.G. Tardi Use of nanoscale delivery systems to maintain synergistic drug ratios in vivo Expert Opin. Drug Deliv. 7 2010 1329 1341
18. X. Dong, C.A. Mattingly, M.T. Tseng, M.J. Cho, Y. Liu, V.R. Adams, and R.J. Mumper Doxorubicin and paclitaxel-loaded lipid-based nanoparticles overcome multidrug resistance by inhibiting P-glycoprotein and depleting ATP Cancer Res. 69 2009 3918 3926
19. S. Doublier, D.C. Belisario, M. Polimeni, L. Annaratone, C. Riganti, E. Allia, D. Ghigo, A. Bosia, and A. Sapino HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast BMC Cancer 12 2012 4
20. R.E. Durand Slow penetration of anthracyclines into spheroids and tumors: a therapeutic advantage? Cancer Chemother. Pharmacol. 26 1990 198 204
21. S.J. Fey, and K. Wrzesinski Determination of drug toxicity using 3D spheroids constructed from an immortal human hepatocyte cell line Toxicol. Sci. 127 2012 403 411
22. C. Fischbach, R. Chen, T. Matsumoto, T. Schmelzle, J.S. Brugge, P.J. Polverini, and D.J. Mooney Engineering tumors with 3D scaffolds Nat. Methods 4 2007 855 860
23. J.P. Freyer, and R.M. Sutherland Selective dissociation and characterization of cells from different regions of multicell tumor spheroids Cancer Res. 40 1980 3956 3965
24. J. Friedrich, R. Ebner, and L.A. Kunz-Schughart Experimental anti-tumor therapy in 3-D: spheroids-old hat or new challenge? Int. J. Radiat. Biol. 83 2007 849 871
25. J. Friedrich, C. Seidel, R. Ebner, and L.A. Kunz-Schughart Spheroid-based drug screen: considerations and practical approach Nat. Protoc. 4 2009 309 324
26. P.T. Gomme, K.B. McCann, and J. Bertolini Transferrin: structure, function and potential therapeutic actions Drug Discov. Today 10 2005 267 273
27. T.T. Goodman, C.P. Ng, and S.H. Pun 3-D tissue culture systems for the evaluation and optimization of nanoparticle-based drug carriers Bioconjug. Chem. 19 2008 1951 1959
28. T.T. Goodman, P.L. Olive, and S.H. Pun Increased nanoparticle penetration in collagenase-treated multicellular spheroids Int. J. Nanomed. 2 2007 265 274
29. S.C. Gupta, C. Sundaram, S. Reuter, and B.B. Aggarwal Inhibiting NF-kappa B activation by small molecules as a therapeutic strategy Biochim. Biophys. Acta - Gene Regul. Mech. 1799 2010 775 787
30. M.D. Hall, C. Martin, D.J. Ferguson, R.M. Phillips, T.W. Hambley, and R. Callaghan Comparative efficacy of novel platinum(IV) compounds with established chemotherapeutic drugs in solid tumour models Biochem. Pharmacol. 67 2004 17 30
31. G. Hamilton Multicellular spheroids as an in vitro tumor model Cancer Lett. 131 1998 29 34
32. M. Han, Y. Bae, N. Nishiyama, K. Miyata, M. Oba, and K. Kataoka Transfection study using multicellular tumor spheroids for screening non-viral polymeric gene vectors with low cytotoxicity and high transfection efficiencies J. Control. Release 121 2007 38 48
33. M. Han, M. Oba, N. Nishiyama, M.R. Kano, S. Kizaka-Kondoh, and K. Kataoka Enhanced percolation and gene expression in tumor hypoxia by PEGylated polyplex micelles Mol. Ther. 17 2009 1404 1410
34. F. Hirschhaeuser, H. Menne, C. Dittfeld, J. West, W. Mueller-Klieser, and L.A. Kunz-Schughart Multicellular tumor spheroids: an underestimated tool is catching up again J. Biotechnol. 148 2010 3 15
35. W.Y. Ho, S.K. Yeap, C.L. Ho, R.A. Rahim, and N.B. Alitheen Development of multicellular tumor spheroid (MCTS) culture from breast cancer cell and a high throughput screening method using the MTT assay PLoS ONE 7 2012 e44640
36. T. Hoevel, R. Macek, K. Swisshelm, and M. Kubbies Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids Int. J. Cancer 108 2004 374 383
37. A.L. Howes, G.G. Chiang, E.S. Lang, C.B. Ho, G. Powis, K. Vuori, and R.T. Abraham The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures Mol. Cancer Ther. 6 2007 2505 2514
38. A. Ivascu, and M. Kubbies Rapid generation of single-tumor spheroids for high-throughput cell function and toxicity analysis J. Biomol. Screen. 11 2006 922 932
39. A. Ivascu, and M. Kubbies Diversity of cell-mediated adhesions in breast cancer spheroids Int. J. Oncol. 31 2007 1403 1413
40. S.H. Jang, M.G. Wientjes, and J.L. Au Kinetics of P-glycoprotein-mediated efflux of paclitaxel J. Pharmacol. Exp. Ther. 298 2001 1236 1242
41. S.H. Jang, M.G. Wientjes, D. Lu, and J.L. Au Drug delivery and transport to solid tumors Pharm. Res. 20 2003 1337 1350
42. M. Juweid, R. Neumann, C. Paik, M.J. Perez-Bacete, J. Sato, W. van Osdol, and J.N. Weinstein Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier Cancer Res. 52 1992 5144 5153
43. A.V. Kabanov, E.V. Batrakova, and V.Y. Alakhov Pluronic block copolymers for overcoming drug resistance in cancer Adv. Drug Deliv. Rev. 54 2002 759 779
44. J.M. Kelm, N.E. Timmins, C.J. Brown, M. Fussenegger, and L.K. Nielsen Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types Biotechnol. Bioeng. 83 2003 173 180
45. D.J. Kerr, T.E. Wheldon, S. Hydns, and S.B. Kaye Cytotoxic drug penetration studies in multicellular tumour spheroids Xenobiotica 18 1988 641 648
46. V.I. Khaoustov, G.J. Darlington, H.E. Soriano, B. Krishnan, D. Risin, N.R. Pellis, and B. Yoffe Induction of three-dimensional assembly of human liver cells by simulated microgravity In Vitro Cell. Dev. Biol. Anim. 35 1999 501 509
47. D. Kim, Z.G. Gao, E.S. Lee, and Y.H. Bae In vivo evaluation of doxorubicin-loaded polymeric micelles targeting folate receptors and early endosomal pH in drug-resistant ovarian cancer Mol. Pharm. 6 2009 1353 1362
48. T.H. Kim, C.W. Mount, W.R. Gombotz, and S.H. Pun The delivery of doxorubicin to 3-D multicellular spheroids and tumors in a murine xenograft model using tumor-penetrating triblock polymeric micelles Biomaterials 31 2010 7386 7397
49. T. Kobayashi, T. Ishida, Y. Okada, S. Ise, H. Harashima, and H. Kiwada Effect of transferrin receptor-targeted liposomal doxorubicin in P-glycoprotein-mediated drug resistant tumor cells Int. J. Pharm. 329 2007 94 102
50. A. Kolchinsky, and I.B. Roninson Drug resistance conferred by MDR1 expression in spheroids formed by glioblastoma cell lines Anticancer Res. 17 1997 3321 3327
51. L.A. Kunz-Schughart Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor Cell Biol. Int. 23 1999 157 161
52. G.Y. Lee, P.A. Kenny, E.H. Lee, and M.J. Bissell Three-dimensional culture models of normal and malignant breast epithelial cells Nat. Methods 4 2007 359 365
53. X.R. Li, P.Z. Li, Y.H. Zhang, Y.X. Zhou, X.W. Chen, Y.Q. Huang, and Y. Liu Novel mixed polymeric micelles for enhancing delivery of anticancer drug and overcoming multidrug resistance in tumor cell lines simultaneously Pharm. Res. 27 2010 1498 1511
54. C.-C. Lin, A. Raza, and H. Shih PEG hydrogels formed by thiol-ene photo-click chemistry and their effect on the formation and recovery of insulin-secreting cell spheroids Biomaterials 32 2011 9685 9695
55. D. Loessner, K.S. Stok, M.P. Lutolf, D.W. Hutmacher, J.A. Clements, and S.C. Rizzi Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells Biomaterials 31 2010 8494 8506
56. J.A. Ludwig, G. Szakacs, S.E. Martin, B.F. Chu, C. Cardarelli, Z.E. Sauna, N.J. Caplen, H.M. Fales, S.V. Ambudkar, J.N. Weinstein, and M.M. Gottesman Selective toxicity of NSC73306 in MDR1-positive cells as a new strategy to circumvent multidrug resistance in cancer Cancer Res. 66 2006 4808 4815
57. A.N. Lukyanov, Z. Gao, L. Mazzola, and V.P. Torchilin Polyethylene glycol-diacyllipid micelles demonstrate increased acculumation in subcutaneous tumors in mice Pharm. Res. 19 2002 1424 1429
58. A.N. Lukyanov, and V.P. Torchilin Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs Adv. Drug Deliv. Rev. 56 2004 1273 1289
59. L.D. Mayer, and A.S. Janoff Optimizing combination chemotherapy by controlling drug ratios Mol. Int. 7 2007 216 223
60. G. Mehta, A.Y. Hsiao, M. Ingram, G.D. Luker, and S. Takayama Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy J. Control. Release 164 2012 192 204
61. A.S. Mikhail, S. Eetezadi, and C. Allen Multicellular tumor spheroids for evaluation of cytotoxicity and tumor growth inhibitory effects of nanomedicines in vitro: a comparison of docetaxel-loaded block copolymer micelles and Taxotere(R) PLoS ONE 8 2013 e62630
62. A.I. Minchinton, and I.F. Tannock Drug penetration in solid tumours Nat. Rev. Cancer 6 2006 583 592
63. L. Mu, T.A. Elbayoumi, and V.P. Torchilin Mixed micelles made of poly(ethylene glycol)-phosphatidylethanolamine conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin Int. J. Pharm. 306 2005 142 149
64. T. Musacchio, V. Laquintana, A. Latrofa, G. Trapani, and V.P. Torchilin PEG-PE micelles loaded with paclitaxel and surface-modified by a PBR-ligand: synergistic anticancer effect Mol. Pharm. 6 2009 468 479
65. K.L. Nair, A.K. Thulasidasan, G. Deepa, R.J. Anto, and G.S. Kumar Purely aqueous PLGA nanoparticulate formulations of curcumin exhibit enhanced anticancer activity with dependence on the combination of the carrier Int. J. Pharm. 425 2012 44 52
66. C.P. Ng, and S.H. Pun A perfusable 3D cell-matrix tissue culture chamber for in situ evaluation of nanoparticle vehicle penetration and transport Biotechnol. Bioeng. 99 2008 1490 1501
67. S.L. Nyberg, J. Hardin, B. Amiot, U.A. Argikar, R.P. Remmel, and P. Rinaldo Rapid, large-scale formation of porcine hepatocyte spheroids in a novel spheroid reservoir bioartificial liver Liver Transpl. 11 2005 901 910
68. A. Oloumi, W. Lam, J.P. Banath, and P.L. Olive Identification of genes differentially expressed in V79 cells grown as multicell spheroids Int. J. Radiat. Biol. 78 2002 483 492
69. S.C. Owen, and M.S. Shoichet Design of three-dimensional biomimetic scaffolds J. Biomed. Mater. Res. A 94 2010 1321 1331
70. H.L. Pahl Activators and target genes of Rel/NF-kappaB transcription factors Oncogene 18 1999 6853 6866
71. F. Pampaloni, E.G. Reynaud, and E.H. Stelzer The third dimension bridges the gap between cell culture and live tissue Nat. Rev. Mol. Cell Biol. 8 2007 839 845
72. N.R. Patel, A. Rathi, D. Mongayt, and V.P. Torchilin Reversal of multidrug resistance by co-delivery of tariquidar (XR9576) and paclitaxel using long-circulating liposomes Int. J. Pharm. 2011
73. Y. Patil, T. Sadhukha, L. Ma, and J. Panyam Nanoparticle-mediated simultaneous and targeted delivery of paclitaxel and tariquidar overcomes tumor drug resistance J. Control. Release 136 2009 21 29
74. F. Perche, N.R. Patel, and V.P. Torchilin Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model J. Control. Release 164 2012 95 102
75. F. Perche, and V.P. Torchilin Cancer cell spheroids as a model to evaluate chemotherapy protocols Cancer Biol. Ther. 13 2012 1205 1213
76. V. Ponce de Leon, and R. Barrera-Rodriguez Changes in P-glycoprotein activity are mediated by the growth of a tumour cell line as multicellular spheroids Cancer Cell Int. 5 2005 20
77. J.A. Romashkova, and S.S. Makarov NF-kappa B is a target of AKT in anti-apoptotic PDGF signalling Nature 401 1999 86 90
78. S.K. Sahoo, W. Ma, and V. Labhasetwar Efficacy of transferrin-conjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer Int. J. Cancer 112 2004 335 340
79. G. Salzano, R. Riehle, G. Navarro, F. Perche, G. de Rosa, and V.P. Torchilin Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: a promising strategy to overcome drug resistance in cancer Cancer Lett. 343 2014 224 231
80. C. Sarisozen, I. Vural, T. Levchenko, A.A. Hincal, and V.P. Torchilin Long-circulating PEG-PE micelles co-loaded with paclitaxel and elacridar (GG918) overcome multidrug resistance Drug Deliv. 19 2012 363 370
81. C. Sarisozen, I. Vural, T. Levchenko, A.A. Hincal, and V.P. Torchilin PEG-PE-based micelles co-loaded with paclitaxel and cyclosporine A or loaded with paclitaxel and targeted by anticancer antibody overcome drug resistance in cancer cells Drug Deliv. 19 2012 169 176
82. R.R. Sawant, A.M. Jhaveri, A. Koshkaryev, F. Qureshi, and V.P. Torchilin The effect of dual ligand-targeted micelles on the delivery and efficacy of poorly soluble drug for cancer therapy J. Drug Target. 21 2013 630 638
83. R.R. Sawant, R.M. Sawant, and V.P. Torchilin Mixed PEG-PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: improved drug solubilization and enhanced in vitro cytotoxicity Eur. J. Pharm. Biopharm.: Off. J. Arbeitsgemeinschaft Pharm. Verfahrenstechnik e.V 70 2008 51 57
84. N. Shah, K. Chaudhari, P. Dantuluri, R.S. Murthy, and S. Das Paclitaxel-loaded PLGA nanoparticles surface modified with transferrin and Pluronic((R))P85, an in vitro cell line and in vivo biodistribution studies on rat model J. Drug Target. 17 2009 533 542
85. M. Shakibaei, T. John, G. Schulze-Tanzil, I. Lehmann, and A. Mobasheri Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis Biochem. Pharmacol. 73 2007 1434 1445
86. C.S. Shin, B. Kwak, B. Han, and K. Park Development of an in vitro 3D tumor model to study therapeutic efficiency of an anticancer drug Mol. Pharm. 10 2013 2167 2175
87. S. Shishodia, H.M. Amin, R. Lai, and B.B. Aggarwal Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma Biochem. Pharmacol. 70 2005 700 713
88. K.L. Sodek, M.J. Ringuette, and T.J. Brown Compact spheroid formation by ovarian cancer cells is associated with contractile behavior and an invasive phenotype Int. J. Cancer 124 2009 2060 2070
89. H. Song, O. David, S. Clejan, C.L. Giordano, H. Pappas-Lebeau, L. Xu, and K.C. O'Connor Spatial composition of prostate cancer spheroids in mixed and static cultures Tissue Eng. 10 2004 1266 1276
90. T. Sonoda, H. Kobayashi, T. Kaku, T. Hirakawa, and H. Nakano Expression of angiogenesis factors in monolayer culture, multicellular spheroid and in vivo transplanted tumor by human ovarian cancer cell lines Cancer Lett. 196 2003 229 237
91. C.N. Sreekanth, S.V. Bava, E. Sreekumar, and R.J. Anto Molecular evidences for the chemosensitizing efficacy of liposomal curcumin in paclitaxel chemotherapy in mouse models of cervical cancer Oncogene 30 2011 3139 3152
92. M. Sugimura, S. Sagae, S. Ishioka, Y. Nishioka, K. Tsukada, and R. Kudo Mechanisms of paclitaxel-induced apoptosis in an ovarian cancer cell line and its paclitaxel-resistant clone Oncology 66 2004 53 61
93. R.M. Sutherland Cell and environment interactions in tumor microregions: the multicell spheroid model Science 240 1988 177 184
94. R.M. Sutherland, J.A. McCredie, and W.R. Inch Growth of multicell spheroids in tissue culture as a model of nodular carcinomas J. Natl. Cancer Inst. 46 1971 113 120
95. V.P. Torchilin Lipid-core micelles for targeted drug delivery Curr. Drug Deliv. 2 2005 319 327
96. V.P. Torchilin, T.S. Levchenko, A.N. Lukyanov, B.A. Khaw, A.L. Klibanov, R. Rammohan, G.P. Samokhin, and K.R. Whiteman P-nitrophenylcarbonyl-PEG-PE-liposomes: fast and simple attachment of specific ligands, including monoclonal antibodies, to distal ends of PEG chains via p-nitrophenylcarbonyl groups Biochim. Biophys. Acta 1511 2001 397 411
97. R. Venkatasubramanian, M.A. Henson, and N.S. Forbes Integrating cell-cycle progression, drug penetration and energy metabolism to identify improved cancer therapeutic strategies J. Theor. Biol. 253 2008 98 117
98. I. Vermes, C. Haanen, H. Steffens-Nakken, and C. Reutelingsperger A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V J. Immunol. Methods 184 1995 39 51
99. P.J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E.H. Stelzer High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy Nat. Methods 4 2007 311 313
100. M. Vinci, S. Gowan, F. Boxall, L. Patterson, M. Zimmermann, W. Court, C. Lomas, M. Mendiola, D. Hardisson, and S.A. Eccles Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation BMC Biol. 10 2012 29
101. J. Walker, C. Martin, and R. Callaghan Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can restore anticancer drug efficacy Eur. J. Cancer 40 2004 594 605
102. T.H. Wang, H.S. Wang, and Y.K. Soong Paclitaxel-induced cell death: where the cell cycle and apoptosis come together Cancer 88 2000 2619 2628
103. M. Wartenberg, K. Fischer, J. Hescheler, and H. Sauer Modulation of intrinsic P-glycoprotein expression in multicellular prostate tumor spheroids by cell cycle inhibitors Biochim. Biophys. Acta 1589 2002 49 62
104. M. Wartenberg, J. Hescheler, H. Acker, H. Diedershagen, and H. Sauer Doxorubicin distribution in multicellular prostate cancer spheroids evaluated by confocal laser scanning microscopy and the "optical probe technique" Cytometry 31 1998 137 145
105. N. Watanabe, R. Hirayama, and N. Kubota The chemopreventive flavonoid apigenin confers radiosensitizing effect in human tumor cells grown as monolayers and spheroids J. Radiat. Res. 48 2007 45 50
106. V. Weissig, K.R. Whiteman, and V.P. Torchilin Accumulation of protein-loaded long-circulating micelles and liposomes in subcutaneous Lewis lung carcinoma in mice Pharm. Res. 15 1998 1552 1556
107. H.L. Wong, R. Bendayan, A.M. Rauth, and X.Y. Wu Simultaneous delivery of doxorubicin and GG918 (Elacridar) by new polymer-lipid hybrid nanoparticles (PLN) for enhanced treatment of multidrug-resistant breast cancer J. Control. Release 116 2006 275 284
108. M.M. Yallapu, M.R. Dobberpuhl, D.M. Maher, M. Jaggi, and S.C. Chauhan Design of curcumin loaded cellulose nanoparticles for prostate cancer Curr. Drug Metab. 13 2012 120 128
109. W. Zhang, Y. Shi, Y. Chen, S. Yu, J. Hao, J. Luo, X. Sha, and X. Fang Enhanced antitumor efficacy by paclitaxel-loaded pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance Eur. J. Pharm. Biopharm.: Off. J. Arbeitsgemeinschaft Pharm. Verfahrenstechnik e.V 75 2010 341 353
110. C.L. Zhao, M.A. Winnik, G. Riess, and M.D. Croucher Fluorescence probe techniques used to study micelle formation in water-soluble block copolymers Langmuir 6 1990 514 516