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

页码：4327 / 4335

页数：9

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