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  • Title: Robust, tumor-homing and redox-sensitive polymersomal doxorubicin: A superior alternative to Doxil and Caelyx?
    Author: Zou Y, Meng F, Deng C, Zhong Z.
    Journal: J Control Release; 2016 Oct 10; 239():149-58. PubMed ID: 27569664.
    Abstract:
    Pegylated liposomal doxorubicin (Lipo-Dox) is one of the few clinically used cancer nanomedicines. Here we show that tumor-homing, redox-responsive and reversibly crosslinked multifunctional biodegradable polymersomes are a better alternative to liposomes for Dox delivery. Cyclic peptide cNGQGEQc-decorated polymersomes (cNGQ-PS) are easily prepared with a small size and high Dox loading. Dox-loaded cNGQ-PS (cNGQ-PS-Dox) shows superb stability with minimal drug leakage under physiological conditions while spontaneous disassembly and quick drug release in response to 10mM glutathione. MTT assays, flow cytometry and confocal microscopy clearly display efficient receptor-mediated internalization of cNGQ-PS-Dox, fast intracellular drug release, and high antitumor activity in α3β1 integrin-overexpressing A549 lung cancer cells. Intriguingly, cNGQ-PS-Dox presents a remarkably high maximum-tolerated dose of over 100mg/kg, over 6-fold higher than Lipo-Dox. The in vivo pharmacokinetics and biodistribution studies reveal that cNGQ-PS-Dox has a long circulation time and significantly enhanced tumor accumulation (8.60%ID/g) as compared to Lipo-Dox and non-targeting PS-Dox controls. Notably, cNGQ-PS-Dox shows superior treatment of both subcutaneous and orthotopic A549 human lung cancer bearing nude mice to Lipo-Dox, resulting in effective tumor suppression, significantly improved survival time, and markedly reduced adverse effects. cNGQ-PS appears to be a clinically viable system for targeted lung cancer chemotherapy.
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