HPMA Copolymer Conjugates of DOX and Mitomycin C for Combination Therapy: Physicochemical Characterization, Cytotoxic Effects, Combination Index Analysis, and Anti-Tumor Efficacy
HPMA Copolymer Conjugates of DOX and Mitomycin C for Combination Therapy: Physicochemical Characterization, Cytotoxic Effects, Combination Index Analysis, and Anti-Tumor Efficacy
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DOI：
10.1002/mabi.201300288
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发表时间：
2013-12-01
影响因子：
4.6
通讯作者：
Ulbrich, Karel
中科院分区：
文献类型：
--
作者：
Kostkova, Hana;Etrych, Tomas;Ulbrich, Karel
本文介绍了抗癌药物阿霉素和丝裂霉素C的HPMA共聚物偶联物的合成、表征和生物学行为评价结果。合成了两种HPMA共聚物载体类型：线性共聚物和含有可降解二硫键的可生物降解的高分子量二嵌段共聚物。在模拟细胞内环境的缓冲液中孵育的聚合物-药物缀合物比在血流条件下孵育的聚合物-药物缀合物更快地释放药物。缀合物在EL-4 T细胞治疗中的显著的体外和体内抗肿瘤协同活性证明了它们用于实体瘤治疗的高潜力。
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.