Enhanced cytotoxicity of a polymer-drug conjugate with triple payload of paclitaxel

被引：62
|
作者：
Erez, Rotem [1 ]
Segal, Ehud [2 ]
Miller, Keren [2 ]
Satchi-Fainaro, Ronit [2 ]
Shabat, Doron [1 ]
机构：
[1] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, Dept Organ Chem, IL-69978 Tel Aviv, Israel
[2] Tel Aviv Univ, Sackler Fac Med Sci, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 13期
关键词：
Prodrug; Conjugate; HPMA copolymer; Self-immolative; Paclitaxel; Polymer therapeutics; ENZYME PRODRUG THERAPY; SELF-IMMOLATIVE DENDRIMERS; HPMA COPOLYMER; ANTICANCER AGENTS; MODEL COMBINATION; NANOMEDICINES; ANGIOGENESIS; DOCETAXEL; TNP-470; CANCER;
D O I：
10.1016/j.bmc.2009.05.028
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：4327 / 4335
页数：9
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