HPMA copolymers for modulating cellular signaling and overcoming multidrug resistance

Advanced Drug Delivery Reviews

Volumn 62, Issue 2, 2010, Pages 192-202

  Minko, Tamara ^a  

^a RUTGERS UNIVERSITY   (United States)

Author keywords

Apoptosis; EPR effect; Gene and protein expression; Macromolecules; Nanotherapeutics; Pump and nonpump resistance; Signal transduction; Tumor hypoxia

Indexed keywords

APOPTOSIS; EPR EFFECT; NANOTHERAPEUTICS; PROTEIN EXPRESSIONS; TUMOR HYPOXIA;

BACTERIOPHAGES; CELL DEATH; COPOLYMERIZATION; DETOXIFICATION; DRUG DELIVERY; ELECTRON RESONANCE; ELECTRON SPIN RESONANCE SPECTROSCOPY; GENE EXPRESSION; MACROMOLECULES; ORGANIC POLYMERS; PARAMAGNETIC RESONANCE; PROTEINS; PUMPS; QUANTUM THEORY; SIGNALING; TUMORS;

SIGNAL TRANSDUCTION;

ABC TRANSPORTER; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; APOPTOTIC PROTEASE ACTIVATING FACTOR 1; CAMPTOTHECIN; CYCLOSPORIN; CYTOCHROME C; DAUNORUBICIN; DOXORUBICIN; FLUOROURACIL; GELDANAMYCIN; GEMCITABINE; GLYCOPROTEIN P; GLYCYLPHENYLALANYLLEUCYLGLYCYL; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 70; HYDROXYPROPYLMETHYLCELLULOSE; MULTIDRUG RESISTANCE PROTEIN; PACLITAXEL; PLATINUM COMPLEX; PROCASPASE 9; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN C JUN; PROTEIN P53; TALAPORFIN; TETRAPEPTIDE; THAPSIGARGIN; UNCLASSIFIED DRUG; VASCULOTROPIN; ACRYLAMIDE DERIVATIVE; N-(2-HYDROXYPROPYL)METHACRYLAMIDE; POLYMER;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CELL DEATH; CELL MEMBRANE PERMEABILITY; CELL REGENERATION; CELL TRANSPORT; DNA REPAIR; DNA REPLICATION; DNA SYNTHESIS; DOWN REGULATION; DRUG DELIVERY SYSTEM; DRUG TRANSPORT; ENDOCYTOSIS; HUMAN; INTERNALIZATION; LIPID PEROXIDATION; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR MECHANICS; MULTIDRUG RESISTANCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TUMOR CELL; ANIMAL; CHEMISTRY; DRUG EFFECTS; DRUG RESISTANCE; PHYSIOLOGY; TUMOR CELL LINE;

ACRYLAMIDES; ANIMALS; CELL DEATH; CELL LINE, TUMOR; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; HUMANS; POLYMERS; SIGNAL TRANSDUCTION;

EID: 75749106657     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.addr.2009.12.002     Document Type: Review

References (128)

1. Kopecek J., Kopeckova P., Minko T., and Lu Z. HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action. Eur. J. Pharm. Biopharm. 50 (2000) 61-81
2. Al-Obaidi H., Brocchini S., and Buckton G. Anomalous properties of spray dried solid dispersions. J. Pharm. Sci. 98 12 (2009) 4724-4737
3. Arun A., and Reddy B.S. In vitro drug release studies of 2-hydroxyethyl acrylate or 2-hydroxypropyl methacrylate-4-{(1E, 4E)-5-[4-(acryloyloxy)phenyl]-3-oxopenta-1, 4-dienyl}phenyl acrylate copolymer beads. J Biomed Mater Res B Appl Biomater 73 (2005) 291-300
4. Barz M., Tarantola M., Fischer K., Schmidt M., Luxenhofer R., Janshoff A., Theato P., and Zentel R. From defined reactive diblock copolymers to functional HPMA-based self-assembled nanoaggregates. Biomacromolecules 9 (2008) 3114-3118
5. Fisher K.D., Stallwood Y., Green N.K., Ulbrich K., Mautner V., and Seymour L.W. Polymer-coated adenovirus permits efficient retargeting and evades neutralising antibodies. Gene Ther. 8 (2001) 341-348
6. Howard K.A., Dash P.R., Read M.L., Ward K., Tomkins L.M., Nazarova O., Ulbrich K., and Seymour L.W. Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA. Biochim. Biophys. Acta 1475 (2000) 245-255
7. Kanwar S.S., Verma H.K., Pathak S., Kaushal R.K., Kumar Y., Verma M.L., Chimni S.S., and Chauhan G.S. Enhancement of ethyl propionate synthesis by poly (AAc-co-HPMA-cl-MBAm)-immobilized Pseudomonas aeruginosa MTCC-4713, exposed to Hg2+ and NH4+ ions. Acta Microbiol. Immunol. Hung. 53 (2006) 195-207
8. Krakovicova H., Etrych T., and Ulbrich K. HPMA-based polymer conjugates with drug combination. Eur J Pharm Sci 37 (2009) 405-412
9. Kreppel F., and Kochanek S. Modification of adenovirus gene transfer vectors with synthetic polymers: a scientific review and technical guide. Mol Ther 16 (2008) 16-29
10. Line B.R., Mitra A., Nan A., and Ghandehari H. Targeting tumor angiogenesis: comparison of peptide and polymer-peptide conjugates. J Nucl Med 46 (2005) 1552-1560
11. Mobley H.L., Chippendale G.R., Swihart K.G., and Welch R.A. Cytotoxicity of the HpmA hemolysin and urease of Proteus mirabilis and Proteus vulgaris against cultured human renal proximal tubular epithelial cells. Infect. Immun. 59 (1991) 2036-2042
12. Nan A., Croft S.L., Yardley V., and Ghandehari H. Targetable water-soluble polymer-drug conjugates for the treatment of visceral leishmaniasis. J Control Release 94 (2004) 115-127
13. Nicoletti S., Seifert K., and Gilbert I.H. N-(2-hydroxypropyl)methacrylamide-amphotericin B (HPMA-AmB) copolymer conjugates as antileishmanial agents. Int J Antimicrob Agents 33 (2009) 441-448
14. Oupicky D., Konak C., Ulbrich K., Wolfert M.A., and Seymour L.W. DNA delivery systems based on complexes of DNA with synthetic polycations and their copolymers. J Cont Release 65 (2000) 149-171
15. Pan H., Kopeckova P., Liu J., Wang D., Miller S.C., and Kopecek J. Stability in plasmas of various species of HPMA copolymer-PGE1 conjugates. Pharm. Res. 24 (2007) 2270-2280
16. Read M.L., Dash P.R., Clark A., Howard K.A., Oupicky D., Toncheva V., Alpar H.O., Schacht E.H., Ulbrich K., and Seymour L.W. Physicochemical and biological characterisation of an antisense oligonucleotide targeted against the bcl-2 mRNA complexed with cationic-hydrophilic copolymers. Eur J Pharm Sci 10 (2000) 169-177
17. Sykova E., and Jendelova P. In vivo tracking of stem cells in brain and spinal cord injury. Prog. Brain Res. 161 (2007) 367-383
18. Wang D., Sima M., Mosley R.L., Davda J.P., Tietze N., Miller S.C., Gwilt P.R., Kopeckova P., and Kopecek J. Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers. Mol Pharm 3 (2006) 717-725
19. York A.W., Zhang Y., Holley A.C., Guo Y., Huang F., and McCormick C.L. Facile synthesis of multivalent folate-block copolymer conjugates via aqueous RAFT polymerization: targeted delivery of siRNA and subsequent gene suppression. Biomacromolecules 10 (2009) 936-943
20. Yuan W., Yang J., Kopeckova P., and Kopecek J. Smart hydrogels containing adenylate kinase: translating substrate recognition into macroscopic motion. J Am Chem Soc 130 (2008) 15760-15761
21. Duncan R. Development of HPMA copolymer-anticancer conjugates: clinical experience and lessons learnt. Adv Drug Deliv Rev 61 (2009) 1131-1148
22. Borgman M.P., Aras O., Geyser-Stoops S., Sausville E.A., and Ghandehari H. Biodistribution of HPMA copolymer-aminohexylgeldanamycin-RGDfK conjugates for prostate cancer drug delivery. Mol Pharm (2009)
23. Caiolfa V.R., Zamai M., Fiorino A., Frigerio E., Pellizzoni C., d'Argy R., Ghiglieri A., Castelli M.G., Farao M., Pesenti E., Gigli M., Angelucci F., and Suarato A. Polymer-bound camptothecin: initial biodistribution and antitumour activity studies. J Control Release 65 (2000) 105-119
24. Chesler L., Goldenberg D.D., Seales I.T., Satchi-Fainaro R., Grimmer M., Collins R., Struett C., Nguyen K.N., Kim G., Tihan T., Bao Y., Brekken R.A., Bergers G., Folkman J., and Weiss W.A. Malignant progression and blockade of angiogenesis in a murine transgenic model of neuroblastoma. Cancer Res. 67 (2007) 9435-9442
25. Chirico G., Collini M., Olivini F., Zamai M., Frigerio E., and Caiolfa V.R. Aggregation properties of a HPMA-camptothecin copolymer in isotonic solutions. Biophys. Chem. 110 (2004) 281-295
26. Chytil P., Etrych T., Konak C., Sirova M., Mrkvan T., Boucek J., Rihova B., and Ulbrich K. New HPMA copolymer-based drug carriers with covalently bound hydrophobic substituents for solid tumour targeting. J Control Release 127 (2008) 121-130
27. Etrych T., Chytil P., Mrkvan T., Sirova M., Rihova B., and Ulbrich K. Conjugates of doxorubicin with graft HPMA copolymers for passive tumor targeting. J Control Release 132 (2008) 184-192
28. Gianasi E., Wasil M., Evagorou E.G., Keddle A., Wilson G., and Duncan R. HPMA copolymer platinates as novel antitumour agents: in vitro properties, pharmacokinetics and antitumour activity in vivo. Eur. J. Cancer 35 (1999) 994-1002
29. Keprtova J., Vyhnakova M., Minarova E., and Kleinwachter V. Effects of daunomycin and its macromolecular analog daunophilin on the proliferation of mammalian cells. Neoplasma 40 (1993) 161-165
30. Lammers T., Subr V., Peschke P., Kuhnlein R., Hennink W.E., Ulbrich K., Kiessling F., Heilmann M., Debus J., Huber P.E., and Storm G. Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy. Br. J. Cancer 99 (2008) 900-910
31. Lammers T., Hennink W.E., and Storm G. Tumour-targeted nanomedicines: principles and practice. Br. J. Cancer 99 (2008) 392-397
32. Lammers T., Subr V., Ulbrich K., Peschke P., Huber P.E., Hennink W.E., and Storm G. Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials 30 (2009) 3466-3475
33. Lin X., Zhang Q., Rice J.R., Stewart D.R., Nowotnik D.P., and Howell S.B. Improved targeting of platinum chemotherapeutics. the antitumour activity of the HPMA copolymer platinum agent AP5280 in murine tumour models. Eur. J. Cancer 40 (2004) 291-297
34. Lu J.M., Peterson C.M., Guo-Shiah J., Gu Z.W., Peterson C.A., Straight R.C., and Kopecek J. Cooperativity between free and N-(2-hydroxypropyl) methacrylamide copolymer bound adriamycin and meso-chlorin e6 monoethylene diamine induced photodynamic therapy in human epithelial ovarian carcinoma in vitro. Int J Oncol 15 (1999) 5-16
35. Lu Z.R., Gao S.Q., Kopeckova P., and Kopecek J. Modification of cyclosporin A and conjugation of its derivative to HPMA copolymers. Bioconjug. Chem. 12 (2001) 129-133
36. Miller K., Erez R., Segal E., Shabat D., and Satchi-Fainaro R. Targeting bone metastases with a bispecific anticancer and antiangiogenic polymer-alendronate-taxane conjugate. Angew. Chem. Int. Ed. Engl. 48 (2009) 2949-2954
37. Nowotnik D.P., and Cvitkovic E. ProLindac (AP5346): a review of the development of an HPMA DACH platinum polymer therapeutic. Adv Drug Deliv Rev 61 (2009) 1214-1219
38. Peterson C.M., Shiah J.G., Sun Y., Kopeckova P., Minko T., Straight R.C., and Kopecek J. HPMA copolymer delivery of chemotherapy and photodynamic therapy in ovarian cancer. Adv. Exp. Med. Biol. 519 (2003) 101-123
39. Putnam D., and Kopecek J. Enantioselective release of 5-fluorouracil from N-(2-hydroxypropyl)methacrylamide-based copolymers via lysosomal enzymes. Bioconjug. Chem. 6 (1995) 483-492
40. Satchi-Fainaro R., Mamluk R., Wang L., Short S.M., Nagy J.A., Feng D., Dvorak A.M., Dvorak H.F., Puder M., Mukhopadhyay D., and Folkman J. Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin. Cancer Cell 7 (2005) 251-261
41. Sood P., Thurmond Jr. K.B., Jacob J.E., Waller L.K., Silva G.O., Stewart D.R., and Nowotnik D.P. Synthesis and characterization of AP5346, a novel polymer-linked diaminocyclohexyl platinum chemotherapeutic agent. Bioconjug. Chem. 17 (2006) 1270-1279
42. Tijerina M., Kopeckova P., and Kopecek J. Correlation of subcellular compartmentalization of HPMA copolymer-Mce6 conjugates with chemotherapeutic activity in human ovarian carcinoma cells. Pharm. Res. 20 (2003) 728-737
43. Borgman M.P., Ray A., Kolhatkar R.B., Sausville E.A., Burger A.M., and Ghandehari H. Targetable HPMA copolymer-aminohexylgeldanamycin conjugates for prostate cancer therapy. Pharm. Res. 26 (2009) 1407-1418
44. Carlisle R.C., Benjamin R., Briggs S.S., Sumner-Jones S., McIntosh J., Gill D., Hyde S., Nathwani A., Subr V., Ulbrich K., Seymour L.W., and Fisher K.D. Coating of adeno-associated virus with reactive polymers can ablate virus tropism, enable retargeting and provide resistance to neutralising antisera. J Gene Med 10 (2008) 400-411
45. Cuchelkar V., Kopeckova P., and Kopecek J. Novel HPMA copolymer-bound constructs for combined tumor and mitochondrial targeting. Mol Pharm 5 (2008) 776-786
46. David A., Kopeckova P., Minko T., Rubinstein A., and Kopecek J. Design of a multivalent galactoside ligand for selective targeting of HPMA copolymer-doxorubicin conjugates to human colon cancer cells. Eur. J. Cancer 40 (2004) 148-157
47. Ding H., Kopeckova P., and Kopecek J. Self-association properties of HPMA copolymers containing an amphipathic heptapeptide. J Drug Target 15 (2007) 465-474
48. Fowers K.D., Callahan J., Byron P., and Kopecek J.I. Preparation of Fab′ from murine IgG2a for thiol reactive conjugation. J Drug Target 9 (2001) 281-294
49. Greco F., Vicent M.J., Penning N.A., Nicholson R.I., and Duncan R. HPMA copolymer-aminoglutethimide conjugates inhibit aromatase in MCF-7 cell lines. J Drug Target 13 (2005) 459-470
50. Hongrapipat J., Kopeckova P., Liu J., Prakongpan S., and Kopecek J. Combination chemotherapy and photodynamic therapy with fab′ fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells. Mol Pharm 5 (2008) 696-709
51. Jelinkova M., Strohalm J., Etrych T., Ulbrich K., and Rihova B. Starlike vs. classic macromolecular prodrugs: two different antibody-targeted HPMA copolymers of doxorubicin studied in vitro and in vivo as potential anticancer drugs. Pharm. Res. 20 (2003) 1558-1564
52. Jensen K.D., Nori A., Tijerina M., Kopeckova P., and Kopecek J. Cytoplasmic delivery and nuclear targeting of synthetic macromolecules. J Control Release 87 (2003) 89-105
53. Johnson R.N., Kopeckova P., and Kopecek J. Synthesis and evaluation of multivalent branched HPMA copolymer-Fab′ conjugates targeted to the B-cell antigen CD20. Bioconjug. Chem. 20 (2009) 129-137
54. Kovar M., Mrkvan T., Strohalm J., Etrych T., Ulbrich K., Stastny M., and Rihova B. HPMA copolymer-bound doxorubicin targeted to tumor-specific antigen of BCL1 mouse B cell leukemia. J Control Release 92 (2003) 315-330
55. Kunath K., Kopeckova P., Minko T., and Kopecek J. HPMA copolymer-anticancer drug-OV-TL16 antibody conjugates. 3. The effect of free and polymer-bound adriamycin on the expression of some genes in the OVCAR-3 human ovarian carcinoma cell line. Eur. J. Pharm. Biopharm. 49 (2000) 11-15
56. Liu J., Kopeckova P., Buhler P., Wolf P., Pan H., Bauer H., Elsasser-Beile U., and Kopecek J. Biorecognition and subcellular trafficking of HPMA copolymer-anti-PSMA antibody conjugates by prostate cancer cells. Mol Pharm 6 (2009) 959-970
57. Lu Z.R., Shiah J.G., Sakuma S., Kopeckova P., and Kopecek J. Design of novel bioconjugates for targeted drug delivery. J Control Release 78 (2002) 165-173
58. Luo Y., Bernshaw N.J., Lu Z.R., Kopecek J., and Prestwich G.D. Targeted delivery of doxorubicin by HPMA copolymer-hyaluronan bioconjugates. Pharm. Res. 19 (2002) 396-402
59. Mitra A., Coleman T., Borgman M., Nan A., Ghandehari H., and Line B.R. Polymeric conjugates of mono- and bi-cyclic alphaVbeta3 binding peptides for tumor targeting. J Control Release 114 (2006) 175-183
60. Morrison J., Briggs S.S., Green N.K., Thoma C., Fisher K.D., Kehoe S., and Seymour L.W. Cetuximab retargeting of adenovirus via the epidermal growth factor receptor for treatment of intraperitoneal ovarian cancer. Hum. Gene Ther. 20 (2009) 239-251
61. Nori A., and Kopecek J. Intracellular targeting of polymer-bound drugs for cancer chemotherapy. Adv Drug Deliv Rev 57 (2005) 609-636
62. Omelyanenko V., Kopeckova P., Prakash R.K., Ebert C.D., and Kopecek J. Biorecognition of HPMA copolymer-adriamycin conjugates by lymphocytes mediated by synthetic receptor binding epitopes. Pharm. Res. 16 (1999) 1010-1019
63. Pan H., Sima M., Kopeckova P., Wu K., Gao S., Liu J., Wang D., Miller S.C., and Kopecek J. Biodistribution and pharmacokinetic studies of bone-targeting N-(2-hydroxypropyl)methacrylamide copolymer-alendronate conjugates. Mol Pharm 5 (2008) 548-558
64. Pechar M., Ulbrich K., Etrych T., Fabra A., Stevenson M., and Seymour L. Oligopeptides as targeting structures in cancer therapy. J Control Release 101 (2005) 376-379
65. Pola R., Studenovsky M., Pechar M., Ulbrich K., Hovorka O., Vetvicka D., and Rihova B. HPMA-copolymer conjugates targeted to tumor endothelium using synthetic oligopeptides. J Drug Target 17 (2009) 773-786
66. Russell-Jones G., McTavish K., McEwan J., Rice J., and Nowotnik D. Vitamin-mediated targeting as a potential mechanism to increase drug uptake by tumours. J Inorg Biochem 98 (2004) 1625-1633
67. Satchi-Fainaro R., Puder M., Davies J.W., Tran H.T., Sampson D.A., Greene A.K., Corfas G., and Folkman J. Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470. Nat. Med. 10 (2004) 255-261
68. Segal E., Pan H., Ofek P., Udagawa T., Kopeckova P., Kopecek J., and Satchi-Fainaro R. Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PLoS ONE 4 (2009) e5233
69. Tang A., Kopeikova P., and Kopeckeva J. Binding and cytotoxicity of HPMA copolymer conjugates to lymphocytes mediated by receptor-binding epitopes. Pharm. Res. 20 (2003) 360-367
70. Wroblewski S., Rihova B., Rossmann P., Hudcovicz T., Rehakova Z., Kopeckova P., and Kopecek J. The influence of a colonic microbiota on HPMA copolymer lectin conjugates binding in rodent intestine. J Drug Target 9 (2001) 85-94
71. Yang N., Ye Z., Li F., and Mahato R.I. HPMA polymer-based site-specific delivery of oligonucleotides to hepatic stellate cells. Bioconjug. Chem. 20 (2009) 213-221
72. Zarabi B., Nan A., Zhuo J., Gullapalli R., and Ghandehari H. Macrophage targeted N-(2-hydroxypropyl)methacrylamide conjugates for magnetic resonance imaging. Mol Pharm 3 (2006) 550-557
73. Zhou Q.H., You Y.Z., Wu C., Huang Y., and Oupicky D. Cyclic RGD-targeting of reversibly stabilized DNA nanoparticles enhances cell uptake and transfection in vitro. J Drug Target 17 (2009) 364-373
74. Kratz F., Abu Ajaj K., and Warnecke A. Anticancer carrier-linked prodrugs in clinical trials. Expert Opin Investig Drugs 16 (2007) 1037-1058
75. Bilim V. Technology evaluation: PK1, Pfizer/Cancer Research UK. Curr Opin Mol Ther 5 (2003) 326-330
76. Rademaker-Lakhai J.M., Terret C., Howell S.B., Baud C.M., De Boer R.F., Pluim D., Beijnen J.H., Schellens J.H., and Droz J.P. A Phase I and pharmacological study of the platinum polymer AP5280 given as an intravenous infusion once every 3 weeks in patients with solid tumors. Clin Cancer Res 10 (2004) 3386-3395
77. Seymour L.W., Ferry D.R., Kerr D.J., Rea D., Whitlock M., Poyner R., Boivin C., Hesslewood S., Twelves C., Blackie R., Schatzlein A., Jodrell D., Bissett D., Calvert H., Lind M., Robbins A., Burtles S., Duncan R., and Cassidy J. Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int J Oncol 34 (2009) 1629-1636
78. Minko T., Kopeckova P., and Kopecek J. Comparison of the anticancer effect of free and HPMA copolymer-bound adriamycin in human ovarian carcinoma cells. Pharm. Res. 16 (1999) 986-996
79. Minko T., Kopeckova P., and Kopecek J. Chronic exposure to HPMA copolymer-bound adriamycin does not induce multidrug resistance in a human ovarian carcinoma cell line. J. Control. Release 59 (1999) 133-148
80. Minko T., Kopeckova P., and Kopecek J. Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma. Int. J. Cancer 86 (2000) 108-117
81. Minko T., Kopeckova P., and Kopecek J. Preliminary evaluation of caspases-dependent apoptosis signaling pathways of free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells. J Control Release 71 (2001) 227-237
82. Minko T., Kopeckova P., Pozharov V., Jensen K.D., and Kopecek J. The influence of cytotoxicity of macromolecules and of VEGF gene modulated vascular permeability on the enhanced permeability and retention effect in resistant solid tumors. Pharm. Res. 17 (2000) 505-514
83. Minko T., Kopeckova P., Pozharov V., and Kopecek J. HPMA copolymer bound adriamycin overcomes MDR1 gene encoded resistance in a human ovarian carcinoma cell line. J Control Release 54 (1998) 223-233
84. Demoy M., Minko T., Kopeckova P., and Kopecek J. Time- and concentration-dependent apoptosis and necrosis induced by free and HPMA copolymer-bound doxorubicin in human ovarian carcinoma cells. J Control Release 69 (2000) 185-196
85. Kasuya Y., Lu Z.R., Kopeckova P., Minko T., Tabibi S.E., and Kopecek J. Synthesis and characterization of HPMA copolymer-aminopropylgeldanamycin conjugates. J Control Release 74 (2001) 203-211
86. Wang D., Kopeckova J.P., Minko T., Nanayakkara V., and Kopecek J. Synthesis of starlike N-(2-hydroxypropyl)methacrylamide copolymers: potential drug carriers. Biomacromolecules 1 (2000) 313-319
87. Szakacs G., Jakab K., Antal F., and Sarkadi B. Diagnostics of multidrug resistance in cancer. Pathol Oncol Res 4 (1998) 251-257
88. van Veen H.W., and Konings W.N. The ABC family of multidrug transporters in microorganisms. Biochim. Biophys. Acta 1365 (1998) 31-36
89. de Vries E.G., Hamilton T.C., Lind M., Dauplat J., Neijt J.P., and Ozols R.F. Advanced ovarian cancer. Drug resistance, supportive care and dose intensity. Ann. Oncol. 4 Suppl 4 (1993) 57-62
90. Kaye S.B. Multidrug resistance: clinical relevance in solid tumours and strategies for circumvention. Curr. Opin. Oncol. 10 Suppl 1 (1998) S15-19
91. Yusuf R.Z., Duan Z., Lamendola D.E., Penson R.T., and Seiden M.V. Paclitaxel resistance: molecular mechanisms and pharmacologic manipulation. Curr Cancer Drug Targets 3 (2003) 1-19
92. Izquierdo M.A., Scheffer G.L., Flens M.J., Shoemaker R.H., Rome L.H., and Scheper R.J. Relationship of LRP-human major vault protein to in vitro and clinical resistance to anticancer drugs. Cytotechnology 19 (1996) 191-197
93. Giannios J., and Ioannidou-Mouzaka L. Molecular aspects of breast and ovarian cancer. Eur. J. Gynaecol. Oncol. 18 (1997) 387-393
94. Saad M., Garbuzenko O.B., and Minko T. Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer. Nanomed 3 (2008) 761-776
95. Minko T., Dharap S.S., Pakunlu R.I., and Wang Y. Molecular targeting of drug delivery systems to cancer. Curr Drug Targets 5 (2004) 389-406
96. Pakunlu R.I., Cook T.J., and Minko T. Simultaneous modulation of multidrug resistance and antiapoptotic cellular defense by MDR1 and BCL-2 targeted antisense oligonucleotides enhances the anticancer efficacy of doxorubicin. Pharm. Res. 20 (2003) 351-359
97. Pakunlu R.I., Wang Y., Tsao W., Pozharov V., Cook T.J., and Minko T. Enhancement of the efficacy of chemotherapy for lung cancer by simultaneous suppression of multidrug resistance and antiapoptotic cellular defense: novel multicomponent delivery system. Cancer Res. 64 (2004) 6214-6224
98. Pakunlu R.I., Wang Y., Saad M., Khandare J.J., Starovoytov V., and Minko T. In vitro and in vivo intracellular liposomal delivery of antisense oligonucleotides and anticancer drug. J. Control. Release 114 (2006) 153-162
99. Wang Y., and Minko T. A novel cancer therapy: combined liposomal hypoxia inducible factor 1 alpha antisense oligonucleotides and an anticancer drug. Biochem. Pharmacol. 68 (2004) 2031-2042
100. Wang Y., Saad M., Pakunlu R.I., Khandare J.J., Garbuzenko O.B., Vetcher A.A., Soldatenkov V.A., Pozharov V.P., and Minko T. Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxia-inducible factor 1{alpha} enhances the efficacy of chemotherapy in drug-resistant tumor. Clin. Cancer Res. 14 (2008) 3607-3616
101. Pakunlu R.I., Wang Y., Tsao W., Pozharov V., Cook T.J., and Minko T. Enhancement of the efficacy of chemotherapy for lung cancer by simultaneous suppression of multidrug resistance and antiapoptotic cellular defense: novel multicomponent delivery system. Cancer Res. 64 (2004) 6214-6224
102. Minko T., Pakunlu R.I., Wang Y., Khandare J.J., and Saad M. New generation of liposomal drugs for cancer. Anticancer Agents Med Chem 6 (2006) 537-552
103. Dharap S.S., Chandna P., Wang Y., Khandare J.J., Qiu B., Stein S., and Minko T. Molecular targeting of BCL2 and BCLXL proteins by synthetic BCL2 homology 3 domain peptide enhances the efficacy of chemotherapy. J. Pharmacol. Exp. Ther. 316 (2006) 992-998
104. Dharap S.S., and Minko T. Targeted proapoptotic LHRH-BH3 peptide. Pharm. Res. 20 (2003) 889-896
105. Minko T., Dharap S.S., and Fabbricatore A.T. Enhancing the efficacy of chemotherapeutic drugs by the suppression of antiapoptotic cellular defense. Cancer Detect. Prev. 27 (2003) 193-202
106. Minko T., Batrakova E.V., Li S., Li Y., Pakunlu R.I., Alakhov V.Y., and Kabanov A.V. Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells. J. Control. Release 105 (2005) 269-278
107. Minko T., Kopeckova P., and Kopecek J. Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma. Int. J. Cancer 86 (2000) 108-117
108. Minko T., Kopeckova P., and Kopecek J. Mechanisms of anticancer action of HPMA copolymer-bound doxorubicin. In: Kahovec J. (Ed). Polymers in Medicine, Wiley-VCH (2001) 35-47
109. Greish K., Fang J., Inutsuka T., Nagamitsu A., and Maeda H. Macromolecular therapeutics: advantages and prospects with special emphasis on solid tumour targeting. Clin. Pharmacokinet. 42 (2003) 1089-1105
110. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv. Enzyme Regul. 41 (2001) 189-207
111. Matsumura Y., and Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent SMANCs. Cancer Res. 46 (1986) 6387-6392
112. Fang J., Sawa T., and Maeda H. Factors and mechanism of, EPR effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv. Exp. Med. Biol. 519 (2003) 29-49
113. Omelyanenko V., Kopeckova P., Gentry C., and Kopecek J. Targetable HPMA copolymer-adriamycin conjugates. Recognition, internalization, and subcellular fate. J Control Release 53 (1998) 25-37
114. Rihova B., Jelinkova M., Strohalm J., Subr V., Plocova D., Hovorka O., Novak M., Plundrova D., Germano Y., and Ulbrich K. Polymeric drugs based on conjugates of synthetic and natural macromolecules. II. Anti-cancer activity of antibody or (Fab′)(2)-targeted conjugates and combined therapy with immunomodulators. J Control Release 64 (2000) 241-261
115. Khandare J., and Minko T. Polymer-drug conjugates: progress in polymeric prodrugs. Progr. Polym. Sci. 31 (2006) 359-397
116. Zalipsky S., Saad M., Kiwan R., Ber E., Yu N., and Minko T. Antitumor activity of new liposomal prodrug of mitomycin C in multidrug resistant solid tumor: insights of the mechanism of action. J. Drug Target. 15 (2007) 518-530
117. Chaudhary K.S., Abel P.D., and Lalani E.N. Role of the Bcl-2 gene family in prostate cancer progression and its implications for therapeutic intervention. Environ. Health Perspect. 107 Suppl 1 (1999) 49-57
118. Chandna P., Saad M., Wang Y., Ber E., Khandare J., Vetcher A.A., Soldatenkov V.A., and Minko T. Targeted proapoptotic anticancer drug delivery system. Mol. Pharm. 4 (2007) 668-678
119. Dharap S.S., Qiu B., Williams G.C., Sinko P., Stein S., and Minko T. Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides. J. Control. Release 91 (2003) 61-73
120. Nishiyama N., Nori A., Malugin A., Kasuya Y., Kopeckova P., and Kopecek J. Free and N-(2-hydroxypropyl)methacrylamide copolymer-bound geldanamycin derivative induce different stress responses in A2780 human ovarian carcinoma cells. Cancer Res. 63 (2003) 7876-7882
121. Minko T., Kopeckova P., Pozharov V., and Kopecek J. HPMA copolymer bound adriamycin overcomes MDR1 gene encoded resistance in a human ovarian carcinoma cell line. J. Control. Release 54 (1998) 223-233
122. Hu S., Snipas S.J., Vincenz C., Salvesen G., and Dixit V.M. Caspase-14 is a novel developmentally regulated protease. J Biol Chem 273 (1998) 29648-29653
123. Slee E.A., Harte M.T., Kluck R.M., Wolf B.B., Casiano C.A., Newmeyer D.D., Wang H.G., Reed J.C., Nicholson D.W., Alnemri E.S., Green D.R., and Martin S.J. Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 144 (1999) 281-292
124. Bruce-Keller A.J., Begley J.G., Fu W., Butterfield D.A., Bredesen D.E., Hutchins J.B., Hensley K., and Mattson M.P. Bcl-2 protects isolated plasma and mitochondrial membranes against lipid peroxidation induced by hydrogen peroxide and amyloid beta-peptide. J Neurochem 70 (1998) 31-39
125. Emir M., Ozisik K., Cagli K., Misirlioglu M., Ozisik P., Iscan Z., Yildirim E., Kilinc K., and Sener E. Effect of erythropoietin on bcl-2 gene expression in rat cardiac myocytes after traumatic brain injury. Transplant. Proc. 36 (2004) 2935-2938
126. Bernardo A., Greco A., Levi G., and Minghetti L. Differential lipid peroxidation, Mn superoxide, and bcl-2 expression contribute to the maturation-dependent vulnerability of oligodendrocytes to oxidative stress. J Neuropathol Exp Neurol 62 (2003) 509-519
127. Minko T. Mechanisms of cellular drug resistance and strategies to overcome it. In: Mahato R.I. (Ed). Biomaterials for Delivery and Targeting of Proteins and Nucleic Acids (2005), CRC Press, Boca Raton, London, New York, Washington, D.C. 461-492
128. Minko T., Khandare J., and Jayant S. Polymeric drugs. In: Matyjaszewski K., Gnanou Y., and Leibler L. (Eds). Macromolecular Engineering: From Precise Macromolecular Synthesis to Macroscopic Material Properties and Application (2007), Wiley-VCH Verlag GmbH & Co, Weinheim. Germany 2541-2595