Core-Shell-Corona Micelle Stabilized by Reversible Cross-Linkage for Intracellular Drug Delivery

Reversibly cross‐linked core–shell–corona micelles based on a triblock copolymer composed of poly(aliphatic ester), polyphosphoester, and poly(ethylene glycol) are reported. The triblock copolymer is synthesized through consecutive ring‐opening polymerization of ε‐caprolactone and 2,4‐dinitrophenylt...

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Bibliographic Details
Published in:Macromolecular rapid communications. 2010-07, Vol.31 (13), p.1201-1206
Main Authors: Wang, Yu-Cai, Li, Yang, Sun, Tian-Meng, Xiong, Meng-Hua, Wu, Juan, Yang, Yi-Yan, Wang, Jun
Format: Article
Language:English
Subjects:
disulfide
drug delivery systems
micelles
polyphosphoesters: shell-cross-linking
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Summary:Reversibly cross‐linked core–shell–corona micelles based on a triblock copolymer composed of poly(aliphatic ester), polyphosphoester, and poly(ethylene glycol) are reported. The triblock copolymer is synthesized through consecutive ring‐opening polymerization of ε‐caprolactone and 2,4‐dinitrophenylthioethyl ethylene phosphate, followed by conjugation of poly(ethylene glycol). After deprotection under mild conditions, the amphiphilic polymer forms core–shell–corona micelles with free thiols in the shell. Cross‐linking of the micelles within the shell reduces their critical micellization concentration and enhances their stability against severe conditions. The redox‐sensitive cross‐linkage allows the facilitated release of entrapped anticancer drugs in the cytoplasm in response to the intracellular reductive environment. With enhanced stability during circulation after administration, and accelerated intracellular drug release at the target site, the biocompatible and biodegradable shell‐cross‐linked polymeric micelle is promising as a drug vehicle for cancer chemotherapy. Biodegradable polymeric micelles with core–shell–corona structures are prepared. Selective cross‐linking of the shell layer stabilizes the micelles against dilution and retards drug release in a non‐reductive environment. However, the release is accelerated intracellularly, which results in enhanced cytotoxicity to A549 cancer cells.
ISSN:1022-1336
1521-3927
DOI:10.1002/marc.200900863