title: HPMA copolymer conjugates of DOX and mitomycin C for combination therapy: physicochemical characterization, cytotoxic effects, combination index analysis, and anti-tumor efficacy.
abstract: The synthesis, characterization and results of evaluation of the biological behavior of HPMA copolymer conjugates bearing anti-cancer drugs doxorubicin and mitomycin C are described. Two HPMA copolymer carrier types were synthesized: the linear copolymer and the biodegradable high-molecular-weight diblock copolymer containing a degradable disulfide bond. The polymer-drug conjugates incubated in buffers modeling the intracellular environment released the drugs more rapidly than those incubated in bloodstream conditions. Significant in vitro and in vivo antitumor synergistic activity of the conjugates in the treatment of EL-4 T-cell demonstrates their high potential for solid tumor treatment.
authors.affiliation: Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic, v.v.i., Heyrovsky Sq. 2, 162 06, Prague 6, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Kostková
authors.forename: Tomáš
authors.initials: T
authors.lastname: Etrych
authors.forename: Blanka
authors.initials: B
authors.lastname: Ríhová
authors.forename: Libor
authors.initials: L
authors.lastname: Kostka
authors.forename: Larisa
authors.initials: L
authors.lastname: Starovoytová
authors.forename: Marek
authors.initials: M
authors.lastname: Kovář
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D004220:Disulfides; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis*; D004359:Drug Therapy, Combination; D005260:Female; D007700:Kinetics; D007982:Levulinic Acids / Q000737:chemistry; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000737:chemistry / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D003603:Cytotoxins; D004220:Disulfides; D004337:Drug Carriers; D007982:Levulinic Acids; D016685:Mitomycin; D004317:Doxorubicin; C032976:N-(2-hydroxypropyl)methacrylamide; C032246:levulinic acid
keywords: HPMA copolymers; Mitomycin C; combination therapy; doxorubicin; tumor treatment