Polymer-drug conjugates for anticancer drug delivery

Critical Reviews in Therapeutic Drug Carrier Systems

Volumn 32, Issue 3, 2015, Pages 215-245

  Wadhwa, Saurabh ^a   Mumper, Russell J ^b  

^a REGENERON PHARMACEUTICALS INC   (United States)

^b UNC Hamner Institute for Drug Safety Sciences   (United States)

Author keywords

Cancer; Covalent; Drug conjugation; Spacer; Sustained release

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ALENDRONIC ACID; ASIALOGLYCOPROTEIN RECEPTOR; CAMPTOTHECIN; CATHEPSIN B; CD71 ANTIGEN; CELL PENETRATING PEPTIDE; CELL SURFACE RECEPTOR; CHITOSAN; DEXTRAN; DRUG CARRIER; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FUNCTIONAL GROUP; GELATIN; GELATINASE A; GELATINASE B; HYALURONIC ACID; MACROGOL; METHOTREXATE; MULTIDRUG RESISTANCE PROTEIN; N (2 HYDROXYPROPYL) METHACRYLAMIDE; POLY ALPHA MALIC ACID; POLY ASPARTIC ACID; POLY BETA MALIC ACID; POLY N (2 HYDROXYETHYL) L GLUTAMINE; POLYGLYCOLIC ACID; POLYLYSINE; POLYMER; PULLULAN; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; DELAYED RELEASE FORMULATION;

BINDING AFFINITY; DRUG CONJUGATION; DRUG CYTOTOXICITY; DRUG DELIVERY SYSTEM; DRUG RELEASE; DRUG SOLUBILITY; DRUG TARGETING; DRUG TUMOR LEVEL; DRUG UPTAKE; GENE OVEREXPRESSION; HUMAN; MOLECULAR WEIGHT; MULTIDRUG RESISTANCE; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RETICULOENDOTHELIAL SYSTEM; REVIEW; SURFACE CHARGE; ANIMAL; CHEMISTRY; DELAYED RELEASE FORMULATION; DRUG RESISTANCE; NEOPLASMS; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; DELAYED-ACTION PREPARATIONS; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; DRUG RESISTANCE, NEOPLASM; HUMANS; NEOPLASMS; POLYMERS;

EID: 84949499170     PISSN: 07434863     EISSN: 2162660X     Source Type: Journal    
DOI: 10.1615/CritRevTherDrugCarrierSyst.2015010174     Document Type: Review

References (160)

1. Cavallaro G, Mariano L, Salmaso S, Caliceti P, Gaetano G. Folate-mediated targeting of polymeric conjugates of gemcitabine. Int J Pharm. 2006;307(2):258-69.
2. Bhatt R, de Vries P, Tulinsky J, Bellamy G, Baker B, Singer JW, Klein P. Synthesis and in vivo antitumor activity of poly(l-glutamic acid) conjugates of 20S-camptothecin. J Med Chem. 2003;46(1):190-3.
3. Li C, Yu DF, Newman RA, Cabral F, Stephens LC, Hunter N, Milas L, Wallace S. Complete regression of well-established tumors using a novel water-soluble poly(l-glutamic acid)-paclitaxel conjugate. Cancer Res. 1998;58(11):2404-9.
4. Chau Y, Padera RF, Dang NM, Langer R. Antitumor efficacy of a novel polymer-peptide-drug conjugate in human tumor xenograft models. Int J Cancer. 2006;118(6):1519-26.
5. Cavallaro G, Pitarresi G, Licciardi M, Giammona G. Polymeric prodrug for release of an antitumoral agent by specific enzymes. Bioconjugate Chem. 2001;12(2):143-51.
6. Ringsdorf H. Structure and properties of pharmacologically active polymers. J Polym Sci C Polym Symp. 1975(51):135-53.
7. Rowland GF, O'Neill GJ, Davies DA. Suppression of tumour growth in mice by a drug-antibody conjugate using a novel approach to linkage. Nature. 1975;255(5508):487-8.
8. Polyak D, Eldar-Boock A, Baabur-Cohen H, Satchi-Fainaro R. Polymer conjugates for focal and targeted delivery of drugs. Polym Adv Technol. 2013;24(9):777-90.
9. Morimoto Y, Sugibayashi K, Sugihara S, Hosoya K, Nozaki S, Ogawa Y. Antitumor agent poly (amino acid) conjugates as a drug carrier in cancer chemotherapy. J Pharmacobiodyn. 1984;7(9):688-98.
10. Shen WC, Ryser HJ. Poly (l-lysine) and poly (d-lysine) conjugates of methotrexate: Different inhibitory effect on drug resistant cells. Mol Pharmacol. 1979;16(2):614-22.
11. Demarre A, Seymour LW, Schacht E. Evaluation of the hydrolytic and enzymatic stability of macromolecular mitomycin C derivatives. J Control Release. 1994;31(1):89-97.
12. Gupte A, Wadhwa S, Mumper RJ. Enhanced intracellular delivery of the reactive oxygen species (ROS)-generating copper chelator D-penicillamine via a novel gelatin-D-penicillamine conjugate. Bioconjugate Chem. 2008;19(7):1382-8.
13. Yokoyama M, Miyauchi M, Yamada N, Okano T, Sakurai Y, Kataoka K, Inoue S. Polymer micelles as novel drug carrier - adriamycin-conjugated poly(ethylene glycol) poly(aspartic acid) block co-polymer. J Control Release. 1990;11(1-3):269-78.
14. Abdellaoui K, Boustta M, Vert M, Morjani H, Manfait M. Metabolite-derived artificial polymers designed for drug targeting, cell penetration and bioresorption. Eur J Pharm Sci. 1998;6(1):61-73.
15. Harada M, Murata J, Sakamura Y, Sakakibara H, Okuno S, Suzuki T. Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats. J Control Release. 2001;71(1):71-86.
16. Nogusa H, Yamamoto K, Yano T, Kajiki M, Hamana H, Okuno S. Distribution characteristics of carboxymethylpullulan-peptide-doxorubicin conjugates in tumor-bearing rats: Different sequence of peptide spacers and doxorubicin contents. Biol Pharm Bull. 2000;23(5):621-6.
17. Lee JY, Choi YS, Suh JS, Kwon YM, Yang VC, Lee SJ, Chung CP, Park YJ. Cell-penetrating chitosan/doxorubicin/TAT conjugates for efficient cancer therapy. Int J Cancer. 2011;128(10):2470-80.
18. Wei X, Senanayake TH, Warren G, Vinogradov SV. Hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity designed for the targeting of CD44-positive and drug-resistant tumors. Bioconjug Chem. 2013;24(4):658-68.
19. Mittapalli RK, Liu X, Adkins CE, Nounou MI, Bohn KA, Terrell TB, Qhattal HS, Geldenhuys WJ, Palmieri D, Steeg PS, Smith QR, Lockman PR. Paclitaxel-hyaluronic nano-conjugates prolong overall survival in a preclinical brain metastases of breast cancer model. Mol Cancer Ther. 2013;(11):2389-99.
20. Minko T, Kopeckova P, Pozharov V, Kopecek J. HPMA copolymer bound adriamycin over-comes MDR1 gene encoded resistance in a human ovarian carcinoma cell line. J Control Release. 1998;54(2):223-33.
21. Shiah JG, Sun Y, Peterson CM, Straight RC, Kopecek J. Antitumor activity of N-(2-hydroxypropyl) methacrylamide copolymer-mesochlorine e6 and adriamycin conjugates in combination treatments. Clin Cancer Res. 2000;6(3):1008-15.
22. Kostková H, Etrych T, Říhová B, Kostka L, Starovoytová L, Kovář M, Ulbrich K. HPMA copolymer conjugates of DOX and mitomycin C for combination therapy: Physicochemical characterization, cytotoxic effects, combination index analysis, and anti-tumor efficacy. Macromol Biosci. 2013;(12):1648-60.
23. Deacon SP, Apostolovic B, Carbajo RJ, Schott AK, Beck K, Vicent MJ, Pineda-Lucena A, Klok HA, Duncan R. Polymer coiled-coil conjugates: Potential for development as a new class of therapeutic "molecular switch." Biomacromolecules. 2011;12(1):19-27.
24. Wadhwa S, Mumper RJ. Polypeptide conjugates of d-penicillamine and idarubicin for anticancer therapy. J Control Release. 2012;158(2):215-23.
25. Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46(12 Pt 1):6387-92.
26. Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol. 2010;7(11): 653-64.
27. Guan H, McGuire MJ, Li S, Brown KC. Peptide-targeted polyglutamic acid doxorubicin conjugates for the treatment of αvβ3-positive cancers. Bioconjugate Chem. 2008;19(9):1813-21.
28. Ye H, Jin L, Hu R, Yi Z, Li J, Wu Y, Xi X, Wu Z. Poly(γ-l-glutamic acid)-cisplatin conjugate effectively inhibits human breast tumor xenografted in nude mice. Biomaterials. 2006;27(35):5958-65.
29. Christie RJ, Grainger DW. Design strategies to improve soluble macromolecular delivery constructs. Adv Drug Deliv Rev. 2003;55(3):421-37.
30. Ofek P, Miller K, Eldar-Boock A, Polyak D, Segal E, Satchi-Fainaro R. Rational design of multifunctional polymer therapeutics for cancer theranostics. Isr J Chem. 2010;50(2):185-203.
31. Takakura Y, Matsumoto S, Hashida M, Sezaki H. Physicochemical properties and antitumor activities of polymeric prodrugs of mitomycin-C with different regeneration rates. J Control Release. 1989;10(1):97-105.
32. Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst. 2006;98(5): 335-44.
33. Seymour LW, Duncan R, Strohalm J, Kopecek J. Effect of molecular weight (MW) of N-(2-hydroxypropyl)methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration to rats. J Biomed Mater Res. 1987;21(11): 1341-58.
34. Mehvar R, Robinson MA, Reynolds JM. Dose dependency of the kinetics of dextrans in rats: Effects of molecular weight. J Pharm Sci. 1995;84(7):815-8.
35. Alshamkhani A, Duncan R. Radioiodination of alginate via covalently-bound tyrosinamide allows monitoring of its fate in vivo. J Bioact Compat Polym. 1995;10(1):4-13.
36. Alshamkhani A, Duncan R. Synthesis, controlled release properties and antitumor activity of alginate-cis-aconityl-daunomycin conjugates. Int J Pharm. 1995;122(1-2):107-19.
37. Lammers T, Kuhnlein R, Kissel M, Subr V, Etrych T, Pola R, Pechar M, Ulbrich K, Storm G, Huber P, Peschke P. Effect of physicochemical modification on the biodistribution and tumor accumulation of HPMA copolymers. J Control Release. 2005;110(1):103-18.
38. Etrych T, Kovar L, Strohalm J, Chytil P, Rihova B, Ulbrich K. Biodegradable star HPMA polymer-drug conjugates: Biodegradability, distribution and anti-tumor efficacy. J Control Release. 2011;154(3): 241-8.
39. Dubowchik GM, Mosure K, Knipe JO, Firestone RA. Cathepsin b-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (taxol), mitomycin c and doxorubicin. Bioorg Med Chem Lett. 1998;8(23):3347-52.
40. Shaffer SA, Baker-Lee C, Kennedy J, Lai MS, de Vries P, Buhler K, Singer JW. In vitro and in vivo metabolism of paclitaxel poliglumex: Identification of metabolites and active proteases. Cancer Chemother Pharmacol. 2007;59(4):537-48.
41. Chen CS, Ofner CM, 3rd. The effect of molecular weight, drug load, and charge of gelatin-MTX conjugates on growth inhibition of HL-60 leukemia cells. Pharm Res. 2009;26(2):338-45.
42. Soukos NS, Hamblin MR, Hasan T. The effect of charge on cellular uptake and phototoxicity of polylysine chlorin(e6) conjugates. Photochem Photobiol. 1997;65(4):723-9.
43. Chau Y, Tan FE, Langer R. Synthesis and characterization of dextran-peptide-methotrexate conjugates for tumor targeting via mediation by matrix metalloproteinase II and matrix metalloproteinase IX. Bioconjugate Chem. 2004;15(4):931-41.
44. Ouchi T, Banba T, Matsumoto T, Suzuki S, Suzuki M. Synthesis and antitumor activity of conjugates of 5-fluorouracil and chito-oligosaccharides involving a hexamethylene spacer group and carbamoyl bonds. Drug Des Deliv. 1990;6(4):281-7.
45. Nogusa H, Yano T, Okuno S, Hamana H, Inoue K. Synthesis of carboxymethylpullulan-peptide-doxorubicin conjugates and their properties. Chem Pharm Bull (Tokyo). 1995;43(11):1931-6.
46. Tabata Y, Kawai T, Murakami Y, Ikada Y. Electric charge influence of dextran derivatives on their tumor accumulation after intravenous injection. Drug Deliv. 1997;4(3):213-21.
47. Hudecz F, Clegg JA, Kajtar J, Embleton MJ, Szekerke M, Baldwin RW. Synthesis, conformation, biodistribution, and in vitro cytotoxicity of daunomycin-branched polypeptide conjugates. Bioconjugate Chem. 1992;3(1):49-57.
48. Abdellaoui K, Boustta M, Morjani H, Manfait M, Vert M. Uptake and intracellular distribution of 4-aminofluorescein-labelled poly(l-lysine citramide imide) in K562 cells. J Drug Target. 1998;5(3): 193-206.
49. Satchi-Fainaro R, Puder M, Davies JW, Tran HT, Sampson DA, Greene AK, Corfas G, Folkman J. Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470. Nat Med. 2004;10(3): 255-61.
50. Minko T, Kopeckova P, Kopecek J. Chronic exposure to HPMA copolymer-bound adriamycin does not induce multidrug resistance in a human ovarian carcinoma cell line. J Control Release. 1999;59(2): 133-48.
51. Omelyanenko V, Kopeckova P, Gentry C, Kopecek J. Targetable HPMA copolymer-adriamycin conjugates. Recognition, internalization, and subcellular fate. J Control Release. 1998;53(1-3):25-37.
52. Greco F, Vicent MJ, Gee S, Jones AT, Gee J, Nicholson RI, Duncan R. Investigating the mechanism of enhanced cytotoxicity of HPMA copolymer-Dox-AGM in breast cancer cells. J Control Release. 2007;117(1):28-39.
53. Jensen KD, Kopeckova P, Bridge JH, Kopecek J. The cytoplasmic escape and nuclear accumulation of endocytosed and microinjected HPMA copolymers and a basic kinetic study in Hep G2 cells. AAPS PharmSci. 2001;3(4):E32.
54. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proc Natl Acad Sci. 1995;92(16):7297-301.
55. Asayama S, Kato H, Kawakami H, Nagaoka S. Carboxymethyl poly(l-histidine) as a new pH-sensitive polypeptide at endosomal/lysosomal pH. Polym Adv Technol. 2007;18(4):329-33.
56. Lavignac N, Nicholls JL, Ferruti P, Duncan R. Poly(amidoamine) conjugates containing doxorubicin bound via an acid-sensitive linker. Macromol Biosci. 2009;9(5):480-7.
57. Erbacher P, Roche AC, Monsigny M, Midoux P. Putative role of chloroquine in gene transfer into a human hepatoma cell line by DNA/lactosylated polylysine complexes. Exp Cell Res. 1996;225(1):186-94.
58. Ciftci K, Levy RJ. Enhanced plasmid DNA transfection with lysosomotropic agents in cultured fibroblasts. Int J Pharm. 2001;218(1-2):81-92.
59. Lindgren M, Hallbrink M, Prochiantz A, Langel U. Cell-penetrating peptides. Trends Pharmacol Sci. 2000;21(3):99-103.
60. Schwarze SR, Hruska KA, Dowdy SF. Protein transduction: Unrestricted delivery into all cells? Trends Cell Biol. 2000;10(7):290-5.
61. Allinquant B, Hantraye P, Mailleux P, Moya K, Bouillot C, Prochiantz A. Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro. J Cell Biol. 1995;128(5):919-27.
62. Calvet S, Doherty P, Prochiantz A. Identification of a signaling pathway activated specifically in the somatodendritic compartment by a heparan sulfate that regulates dendrite growth. J Neurosci. 1998;18(23):9751-65.
63. Fawell S, Seery J, Daikh Y, Moore C, Chen LL, Pepinsky B, Barsoum J. Tat-mediated delivery of heterologous proteins into cells. Proc Natl Acad Sci. 1994;91(2):664-8.
64. Schwarze SR, Ho A, Vocero-Akbani A, Dowdy SF. In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science. 1999;285(5433):1569-72.
65. Rogers KE, Carr BI, Tokes ZA. Cell surface-mediated cytotoxicity of polymer-bound adriamycin against drug-resistant hepatocytes. Cancer Res. 1983;43(6):2741-8.
66. Tokes ZA, Rogers KE, Rembaum A. Synthesis of adriamycin-coupled polyglutaraldehyde micro-spheres and evaluation of their cytostatic activity. Proc Natl Acad Sci. 1982;79(6):2026-30.
67. Segal E, Pan H, Ofek P, Udagawa T, Kopeckova P, Kopecek J, Satchi-Fainaro R. Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics. PLoS One. 2009;4(4): e5233.
68. Erez R, Segal E, Miller K, Satchi-Fainaro R, Shabat D. Enhanced cytotoxicity of a polymer-drug conjugate with triple payload of paclitaxel. Biorg Med Chem. 2009;17(13):4327-35.
69. Davidson B, Goldberg I, Kopolovic J, Lerner-Geva L, Gotlieb WH, Ben-Baruch G, Reich R. MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma-a clinicopathologic study using immunohistochemistry and mRNA in situ hybridization. Gynecol Oncol. 1999;73(3):372-82.
70. Passlick B, Sienel W, Seen-Hibler R, Wockel W, Thetter O, Mutschler W, Pantel K. Overexpression of matrix metalloproteinase 2 predicts unfavorable outcome in early-stage non-small cell lung cancer. Clin Cancer Res. 2000;6(10):3944-8.
71. Liu Z, Li L, Yang Z, Luo W, Li X, Yang H, Yao K, Wu B, Fang W. Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC cancer. 2010;10:270.
72. Campo E, Munoz J, Miquel R, Palacin A, Cardesa A, Sloane BF, Emmert-Buck MR. Cathepsin B expression in colorectal carcinomas correlates with tumor progression and shortened patient survival. Am J Pathol. 1994;145(2):301-9.
73. Turk V, Turk B, Turk D. Lysosomal cysteine proteases: Facts and opportunities. EMBO J. 2001;20(17): 4629-33.
74. Duncan R, Hume IC, Kopeckova P, Ulbrich K, Strohalm J, Kopecek J. Anticancer agents coupled to N-(2-hydroxypropyl) methacrylamide copolymers 3. Evaluation of adriamycin conjugates against mouse leukemia l1210 in vivo. J Control Release. 1989;10(1):51-63.
75. Nogusa H, Yano T, Kashima N, Yamamoto K, Okuno S, Hamana H. Structure-activity relationships of carboxymethylpullulan-peptide-doxorubicin conjugates-systematic modification of peptide spacers. Bioorg Med Chem Lett. 2000;10(3):227-30.
76. Hoes CJT, Potman W, Van Heeswijk WAR, Mud J, De Grooth BG, Greve J, Feijen J. Optimization of macromolecular prodrugs of the antitumor antibiotic adriamycin. J Control Release. 1985;2:205-14.
77. Ghosh SC, Auzenne E, Khodadadian M, Farquhar D, Klostergaard J. N,N-dimethylsphingosine conjugates of poly-l-glutamic acid: Synthesis, characterization, and initial biological evaluation. Bioorg Med Chem Lett. 2009;19(3):1012-7.
78. Lee RJ, Wang S, Low PS. Measurement of endosome pH following folate receptor-mediated endocytosis. Biochim Biophys Acta. 1996;1312(3):237-42.
79. Mellman I, Fuchs R, Helenius A. Acidification of the endocytic and exocytic pathways. Annu Rev Biochem. 1986;55:663-700.
80. Shen WC, Ryser HJ. Cis-aconityl spacer between daunomycin and macromolecular carriers: A model of pH-sensitive linkage releasing drug from a lysosomotropic conjugate. Biochem Biophys Res Commun. 1981;102(3):1048-54.
81. Yuan H, Luo K, Lai Y, Pu Y, He B, Wang G, Wu Y, Gu Z. A novel poly(l-glutamic acid) dendrimer based drug delivery system with both pH-sensitive and targeting functions. Mol Pharm. 2010;7(4): 953-62.
82. She W, Luo K, Zhang C, Wang G, Geng Y, Li L, He B, Gu Z. The potential of self-assembled, pH-responsive nanoparticles of m-PEGylated peptide dendron-doxorubicin conjugates for cancer therapy. Biomaterials. 2013;34(5):1613-23.
83. Scomparin A, Salmaso S, Bersani S, Saatchi-Fainaro R, Calceti P. Novel folated and non-folated pullulan bioconjugates for anticancer drug delivery. Eur J Pharm Sci. 2011;42(5):547-58.
84. Ulbrich K, Etrych T, Chytil P, Jelinkova M, Rihova B. HPMA copolymers with pH-controlled release of doxorubicin: In vitro cytotoxicity and in vivo antitumor activity. J Control Release. 2003;87(1-3):33-47.
85. Kovar M, Kovar L, Subr V, Etrych T, Ulbrich K, Mrkvan T, Loucka J, Rihova B. HPMA copolymers containing doxorubicin bound by a proteolytically or hydrolytically cleavable bond: Comparison of biological properties in vitro. J Control Release. 2004;99(2):301-14.
86. Choi WM, Kopeckova P, Minko T, Kopecek J. Synthesis of HPMA copolymer containing adriamycin bound via an acid-labile spacer and its activity toward human ovarian carcinoma cells. J Bioact Compat Polym. 1999;14(6):447-56.
87. Kiew LV, Cheong SK, Sidik K, Chung LY. Improved plasma stability and sustained release profile of gemcitabine via polypeptide conjugation. Int J Pharm. 2010;391(1-2):212-20.
88. Ross S, Spencer SD, Holcomb I, Tan C, Hongo J, Devaux B, Rangell L, Keller GA, Schow P, Steeves RM, Lutz RJ, Frantz G, Hillan K, Peale F, Tobin P, Eberhard D, Rubin MA, Lasky LA, Koeppen H. Prostate stem cell antigen as therapy target: Tissue expression and in vivo efficacy of an immunoconjugate. Cancer Res. 2002;62(9):2546-53.
89. Liu C, Tadayoni BM, Bourret LA, Mattocks KM, Derr SM, Widdison WC, Kedersha NL, Ariniello PD, Goldmacher VS, Lambert JM, Blattler WA, Chari RV. Eradication of large colon tumor xenografts by targeted delivery of maytansinoids. Proc Natl Acad Sci. 1996;93(16):8618-23.
90. Cuchelkar V, Kopeckova P, Kopecek J. Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates. Macromol Biosci. 2008;8(5):375-83.
91. Yang J, Chen H, Vlahov IR, Cheng JX, Low PS. Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging. Proc Natl Acad Sci. 2006;103(37):13872-7.
92. Shen WC, Ryser HJ, LaManna L. Disulfide spacer between methotrexate and poly(d-lysine). A probe for exploring the reductive process in endocytosis. J Biol Chem. 1985;260(20):10905-8.
93. Feener EP, Shen WC, Ryser HJ. Cleavage of disulfide bonds in endocytosed macromolecules. A processing not associated with lysosomes or endosomes. J Biol Chem. 1990;265(31):18780-5.
94. Austin CD, Wen X, Gazzard L, Nelson C, Scheller RH, Scales SJ. Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates. Proc Natl Acad Sci. 2005;102(50):17987-92.
95. Arunachalam B, Phan UT, Geuze HJ, Cresswell P. Enzymatic reduction of disulfide bonds in lysosomes: Characterization of a γ-interferon-inducible lysosomal thiol reductase (GILT). Proc Natl Acad Sci. 2000;97(2):745-50.
96. Noiva R. Protein disulfide isomerase: The multifunctional redox chaperone of the endoplasmic reticulum. Semin Cell Dev Biol. 1999;10(5):481-93.
97. Collins DS, Unanue ER, Harding CV. Reduction of disulfide bonds within lysosomes is a key step in antigen processing. J Immunol. 1991;147(12):4054-9.
98. Gao W, Langer R, Farokhzad OC. Poly(ethylene glycol) with observable shedding. Angew Chem. 2010;49(37):6567-71.
99. Ulbrich K, Subr V, Strohalm J, Plocova D, Jelinkova M, Rihova B. Polymeric drugs based on conjugates of synthetic and natural macromolecules. I. Synthesis and physico-chemical characterisation. J Control Release. 2000;64(1-3):63-79.
100. Wen X, Jackson EF, Price RE, Kim EE, Wu Q, Wallace S, Charnsangavej C, Gelovani JG, Li C. Synthesis and characterization of poly(l-glutamic acid) gadolinium chelate: A new biodegradable MRI contrast agent. Bioconjugate Chem. 2004;15(6):1408-15.
101. Bae YH, Park K. Targeted drug delivery to tumors: Myths, reality and possibility. J Control Release. 2011;153(3):198-205.
102. Duncan R. Development of HPMA copolymer-anticancer conjugates: Clinical experience and lessons learnt. Adv Drug Deliv Rev. 2009;61(13):1131-48.
103. Iyer AK, Greish K, Seki T, Okazaki S, Fang J, Takeshita K, Maeda H. Polymeric micelles of zinc protoporphyrin for tumor targeted delivery based on EPR effect and singlet oxygen generation. J Drug Target. 2007;15(7-8):496-506.
104. Zalipsky S, Saad M, Kiwan R, Ber E, Yu N, 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. 2007;15(7-8):518-30.
105. Bae YH. Drug targeting and tumor heterogeneity. J Control Release. 2009;133(1):2-3.
106. Yuan F, Krol A, Tong S. Available space and extracellular transport of macromolecules: Effects of pore size and connectedness. Ann Biomed Eng. 2001;29(12):1150-8.
107. McDaniel JR, Callahan DJ, Chilkoti A. Drug delivery to solid tumors by elastin-like polypeptides. Adv Drug Deliv Rev. 2010;62(15):1456-67.
108. Liu W, Dreher MR, Furgeson DY, Peixoto KV, Yuan H, Zalutsky MR, Chilkoti A. Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice. J Control Release. 2006;116(2):170-8.
109. Trissel LA. Pharmaceutical properties of paclitaxel and their effects on preparation and administration. Pharmacotherapy. 1997;17(5 Pt 2):133S-9S.
110. Greenwald RB, Pendri A, Bolikal D. Highly water-soluble taxol derivatives: 7-polyethylene glycol carbamates and carbonates. J Org Chem. 1995;60(2):331-6.
111. Greenwald RB. PEG drugs: An overview. J Control Release. 2001 Jul 6;74(1-3):159-71.
112. Khandare J, Minko T. Polymer-drug conjugates: Progress in polymeric prodrugs. Prog Polym Sci. 2006;31(4):359-97.
113. Singer JW, De Vries P, Bhatt R, Tulinsky J, Klein P, Li C, Milas L, Lewis RA, Wallace S. Conjugation of camptothecins to poly-(l-glutamic acid). Ann NY Acad Sci. 2000;922:136-50.
114. Li C, Price JE, Milas L, Hunter NR, Ke S, Yu DF, Charnsangavej C, Wallace S. Antitumor activity of poly(l-glutamic acid)-paclitaxel on syngeneic and xenografted tumors. Clin Cancer Res. 1999;5(4):891-7.
115. Gautier S, Boustta M, Vert M. Poly (l-lysine citramide), a water-soluble bioresorbable carrier for drug delivery: Aqueous solution properties of hydrophobized derivatives. J Bioact Compat Polym. 1997;12(2):77-98.
116. Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, Baker JR, Jr., Van Echo DA, Von Hoff DD, Leyland-Jones B. Hypersensitivity reactions from taxol. J Clin Oncol. 1990;8(7): 1263-8.
117. Eldar-Boock A, Miller K, Sanchis J, Lupu R, Vicent MJ, Satchi-Fainaro R. Integrin-assisted drug delivery of nano-scaled polymer therapeutics bearing paclitaxel. Biomaterials. 2011;32(15):3862-74.
118. Kim MS, Dayananda K, Choi EY, Park HJ, Kim JS, Lee DS. Synthesis and characterization of poly(l-glutamic acid)-block-poly(l-phenylalanine). Polymer. 2009;50(10):2252-7.
119. Fan HL, Huang J, Li YP, Yu JH, Chen JH. Fabrication of reduction-degradable micelle based on disulfide-linked graft copolymer-camptothecin conjugate for enhancing solubility and stability of camptothecin. Polymer. 2010;51(22):5107-14.
120. MacKay JA, Chen M, McDaniel JR, Liu W, Simnick AJ, Chilkoti A. Self-assembling chimeric polypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection. Nat Mater. 2009;8(12):993-9.
121. Dreher MR, Raucher D, Balu N, Michael Colvin O, Ludeman SM, Chilkoti A. Evaluation of an elastin-like polypeptide-doxorubicin conjugate for cancer therapy. J Control Release. 2003;91(1-2):31-43.
122. Dey S, Sreenivasan K. Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin. Carbohydr Polym. 2014;99:499-507.
123. Manju S, Sreenivasan K. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability. J Colloid Interface Sci. 2011;359(1):318-25.
124. Vega J, Ke S, Fan Z, Wallace S, Charsangavej C, Li C. Targeting doxorubicin to epidermal growth factor receptors by site-specific conjugation of c225 to poly(l-glutamic acid) through a polyethylene glycol spacer. Pharm Res. 2003;20(5):826-32.
125. Cuchelkar V, Kopeckova P, Kopecek J. Novel HPMA copolymer-bound constructs for combined tumor and mitochondrial targeting. Mol Pharm. 2008;5(5):776-86.
126. Huang J, Gao F, Tang XX, Yu JH, Wang DX, Liu SY, Li YP. Liver-targeting doxorubicin-conjugated polymeric prodrug with pH-triggered drug release profile. Polym Int. 2010;59(10):1390-6.
127. David A, Kopeckova P, Rubinstein A, Kopecek J. Enhanced biorecognition and internalization of HPMA copolymers containing multiple or multivalent carbohydrate side-chains by human hepatocarcinoma cells. Bioconjugate Chem. 2001;12(6):890-9.
128. Line BR, Mitra A, Nan A, Ghandehari H. Targeting tumor angiogenesis: Comparison of peptide and polymer-peptide conjugates. J Nucl Med. 2005;46(9):1552-60.
129. Mitra A, Coleman T, Borgman M, Nan A, Ghandehari H, Line BR. Polymeric conjugates of mono-and bi-cyclic αvβ3 binding peptides for tumor targeting. J Control Release. 2006;114(2):175-83.
130. Borgman MP, Ray A, Kolhatkar RB, Sausville EA, Burger AM, Ghandehari H. Targetable HPMA copolymer-aminohexylgeldanamycin conjugates for prostate cancer therapy. Pharm Res. 2009;26(6):1407-18.
131. Lu ZR, Kopeckova P, Kopecek J. Polymerizable Fab' antibody fragments for targeting of anticancer drugs. Nat Biotechnol. 1999;17(11):1101-4.
132. Nogusa H, Yano T, Kajiki M, Gonsho A, Hamana H, Okuno S. Antitumor effects and toxicities of carboxymethylpullulan-peptide-doxorubicin conjugates. Biol Pharm Bull. 1997;20(10):1061-5.
133. Kovar M, Strohalm J, Ulbrich K, Rihova B. In vitro and in vivo effect of HPMA copolymer-bound doxorubicin targeted to transferrin receptor of B-cell lymphoma 38C13. J Drug Target. 2002;10(1):23-30.
134. Pasut G, Veronese FM. Polymer-drug conjugation, recent achievements and general strategies. Prog Polym Sci. 2007;32(8-9):933-61.
135. Bae Y, Diezi TA, Zhao A, Kwon GS. Mixed polymeric micelles for combination cancer chemo-therapy through the concurrent delivery of multiple chemotherapeutic agents. J Control Release. 2007;122(3):324-30.
136. Zhou D, Xiao H, Meng F, Li X, Li Y, Jing X, Huang Y. A polymer-(tandem drugs) conjugate for enhanced cancer treatment. Adv Healthc Mater. 2013;2(6):822-7.
137. Marklein D, Graab U, Naumann I, Yan T, Ridzewski R, Nitzki F, Rosenberger A, Dittmann K, Wienands J, Wojnowski L, Fulda S, Hahn H. PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells. PLoS One. 2012;7(12):e52898.
138. Vicent MJ, Greco F, Nicholson RI, Paul A, Griffiths PC, Duncan R. Polymer therapeutics designed for a combination therapy of hormone-dependent cancer. Angew Chem. 2005;44(26):4061-6.
139. Lammers T, Subr V, Ulbrich K, Peschke P, Huber PE, Hennink WE, Storm G. Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials. 2009;30(20):3466-75.
140. Krakovicova H, Etrych T, Ulbrich K. HPMA-based polymer conjugates with drug combination. Eur J Pharm Sci. 2009;37(3-4):405-12.
141. Miller K, Erez R, Segal E, Shabat D, Satchi-Fainaro R. Targeting bone metastases with a bi-specific anticancer and antiangiogenic polymer-alendronate-taxane conjugate. Angew Chem. 2009;48(16):2949-54.
142. Wang E, Xiong H, Zhou D, Xie Z, Huang Y, Jing X, Sun X. Co-delivery of oxaliplatin and demethyl-cantharidin via a polymer-drug conjugate. Macromol Biosci. 2014;14(4):588-96.
143. Zhu G, Cao X, Chang JY, Milas L, Wallace S, Li C. Polymeric retinoid prodrug PG-4HPR enhances the radiation response of lung cancer. Oncol Rep. 2007;18(3):645-51.
144. Lu X, Ping Y, Xu FJ, Li ZH, Wang QQ, Chen JH, Yang WT, Tang GP. Bifunctional conjugates comprising β-cyclodextrin, polyethylenimine, and 5-fluoro-2'-deoxyuridine for drug delivery and gene transfer. Bioconjugate Chem. 2010;21(10):1855-63.
145. Li F, Zhang H, Gu C, Fan L, Qiao Y, Tao Y, Cheng C, Wu H, Yi J. Self-assembled nanoparticles from folate-decorated maleilated pullulan-doxorubicin conjugate for improved drug delivery to cancer cells. Polym Int. 2013;62(2):165-71.
146. Jung B, Jeong YC, Min JH, Kim JE, Song YJ, Park JK, Park JH, Kim JD. Tumor-binding prodrug micelles of polymer-drug conjugates for anticancer therapy in HeLa cells. J Mater Chem. 2012;22(18):9385-94.
147. Wang Y, Ma S, Xie Z, Zhang H. A synergistic combination therapy with paclitaxel and doxorubicin loaded micellar nanoparticles. Colloids Surf B Biointerfaces. 2013;116C:41-8.
148. Soo PL, Dunne M, Liu J, Allen C. Nano-sized advanced delivery systems as parenteral formulation strategies for hydrophobic anti-cancer drugs. In: Villiers MM, Aramwit P, Kwon GS, editors. Nanotechnology in drug delivery. New York (NY): Springer; 2009. pp. 349-83.
149. Vasey PA, Kaye SB, Morrison R, Twelves C, Wilson P, Duncan R, Thomson AH, Murray LS, Hilditch TE, Murray T, Burtles S, Fraier D, Frigerio E, Cassidy J. Phase I clinical and pharmaco-kinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: First member of a new class of chemotherapeutic agents-drug-polymer conjugates. Cancer research campaign Phase I/II committee. Clin Cancer Res. 1999;5(1):83-94.
150. Seymour LW, Ferry DR, Kerr DJ, 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, Cassidy J. Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int J Oncol. 2009;34(6):1629-36.
151. Seymour LW, Ferry DR, Anderson D, Hesslewood S, Julyan PJ, Poyner R, Doran J, Young AM, Burtles S, Kerr DJ. Hepatic drug targeting: Phase I evaluation of polymer-bound doxorubicin. J Clin Oncol. 2002;20(6):1668-76.
152. Chipman SD, Oldham FB, Pezzoni G, Singer JW. Biological and clinical characterization of Paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomed. 2006;1(4):375-83.
153. Langer CJ, O'Byrne KJ, Socinski MA, Mikhailov SM, Lesniewski-Kmak K, Smakal M, Ciuleanu TE, Orlov SV, Dediu M, Heigener D, Eisenfeld AJ, Sandalic L, Oldham FB, Singer JW, Ross HJ. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naive advanced non-small cell lung cancer. J Thorac Oncol. 2008;3(6):623-30.
154. Bhatt R, Vries PD, Klein PJ, Tulinsky J, Lewis RA, Singer JW, inventors; Polyglutamic acid-camptothecin conjugates and methods of preparation. US patent 7,153,864.
155. Singer JW, Bhatt R, Tulinsky J, Buhler KR, Heasley E, Klein P, de Vries P. Water-soluble poly-(l-glutamic acid)-GLY-camptothecin conjugates enhance camptothecin stability and efficacy in vivo. J Control Release. 2001;74(1-3):243-7.
156. Soepenberg O, de Jonge MJ, Sparreboom A, de Bruin P, Eskens FA, de Heus G, Wanders J, Cheverton P, Ducharme MP, Verweij J. Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors. Clin Cancer Res. 2005;11(2 Pt 1):703-11.
157. Satchi-Fainaro R, Hailu H, Davies JW, Summerford C, Duncan R. PDEPT: Polymer-directed enzyme prodrug therapy. 2. HPMA copolymer-β-lactamase and HPMA copolymer-C-Dox as a model combination. Bioconjugate Chem. 2003;14(4):797-804.
158. Feng X, Lv F, Liu L, Tang H, Xing C, Yang Q, Wang S. Conjugated polymer nanoparticles for drug delivery and imaging. ACS Appl Mater Interfaces. 2010;2(8):2429-35.
159. Yang Y, Pan D, Luo K, Li L, Gu Z. Biodegradable and amphiphilic block copolymer-doxorubicin conjugate as polymeric nanoscale drug delivery vehicle for breast cancer therapy. Biomaterials. 2013;34(33):8430-43.
160. Satchi R, Connors TA, Duncan R. PDEPT: Polymer-directed enzyme prodrug therapy. I. HPMA copolymer-cathepsin B and PK1 as a model combination. Br J Cancer. 2001;85(7):1070-6.