Enhanced cytotoxicity of a polymer-drug conjugate with triple payload of paclitaxel
Enhanced cytotoxicity of a polymer-drug conjugate with triple payload of paclitaxel
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DOI：
10.1016/j.bmc.2009.05.028
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发表时间：
2009-07-01
影响因子：
3.5
通讯作者：
Shabat, Doron
中科院分区：
文献类型：
--
作者：
Erez, Rotem;Segal, Ehud;Shabat, Doron
开发靶向方法以选择性地将化疗药物释放到恶性组织中是抗癌治疗中的主要挑战。我们合成了一种含有AB（3）自分解树枝状连接基的N-（2-羟丙基）-甲基丙烯酰胺（HPMA）共聚物-药物偶联物。已知HPMA共聚物在肿瘤中选择性地积聚。水溶性聚合物-药物缀合物被设计为由于内源酶组织蛋白酶B的切割而释放疏水药物紫杉醇的三重有效载荷。与经典的单体药物-聚合物缀合物相比，聚合物-药物缀合物对鼠前列腺腺癌（TRAMP C2）细胞表现出增强的细胞毒性。(C)2009爱思唯尔有限公司保留所有权利。
The development of targeting approaches to selectively release chemotherapeutic drugs into malignant tissue is a major challenge in anticancer therapy. We have synthesized an N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer-drug conjugate with an AB(3) self-immolative dendritic linker. HPMA copolymers are known to accumulate selectively in tumors. The water-soluble polymer-drug conjugate was designed to release a triple payload of the hydrophobic drug paclitaxel as a result of cleavage by the endogenous enzyme cathepsin B. The polymer-drug conjugate exhibited enhanced cytotoxicity on murine prostate adenocarcinoma (TRAMP C2) cells in comparison to a classic monomeric drug-polymer conjugate. (C) 2009 Elsevier Ltd. All rights reserved.