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

Rotem Erez; Ehud Segal; Keren Miller; Ronit Satchi-Fainaro; Doron Shabat

doi:10.1016/j.bmc.2009.05.028

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

Rotem Erez, Ehud Segal, Keren Miller, Ronit Satchi-Fainaro, Doron Shabat^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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 AB₃ 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.

Original language	English
Pages (from-to)	4327-4335
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2009.05.028
State	Published - 1 Jul 2009

Keywords

Conjugate
HPMA copolymer
Paclitaxel
Polymer therapeutics
Prodrug
Self-immolative

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10.1016/j.bmc.2009.05.028

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abstract = "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 AB3 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.",

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AU - Segal, Ehud

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AU - Satchi-Fainaro, Ronit

AU - Shabat, Doron

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AB - 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 AB3 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.

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

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