PEGylated Poly(α-lipoic acid) Loaded with Doxorubicin as a pH and Reduction Dual Responsive Nanomedicine for Breast Cancer Therapy.
Authors of this article are:
Yang H, Shen W, Liu W, Chen L, Zhang P, Xiao C, Chen X.
A summary of the article is shown below:
Disulfide-containing nanoparticles are promising vehicles for anticancer drug delivery. However, the preparation of disulfide-containing nanoparticles usually relies on complex synthetic procedures. In the present work, a PEGylated poly(α-lipoic acid) (mPEG-PαLA) copolymer was facilely synthesized and used for pH and reduction dual responsive drug delivery. Poly(α-lipoic acid) was prepared by thermal polymerization of α-lipoic acid without any catalyst or solvent and then conjugated with methoxy poly(ethylene glycol) to form the mPEG-PαLA copolymer. The obtained mPEG-PαLA copolymer was amphiphilic, which could self-assemble into nanoparticles (NPs) in aqueous solution. More interestingly, the mPEG-PαLA NPs showed high drug loading efficiency (87.7%) for the cationic drug doxorubicin (DOX). The DOX-loaded NPs (NPs-DOX) exhibited pH and reduction dual responsive drug release behaviors. Moreover, the flow cytometry analysis and confocal laser scanning microscopy confirmed that the drug-loaded nanoparticles could be efficiently internalized and subsequently release DOX in 4T1 cancer cells. As a result, the NPs-DOX displayed favorable antiproliferation efficacy in 4T1 cancer cells (measured by MTT assays). Furthermore, the NPs-DOX showed enhanced antitumor efficacy in a 4T1 tumor-bearing mice model with reduced side toxicities toward normal organs due to the prolonged circulation time and improved biodistribution in vivo. In other words, this work demonstrates that the PEGylated poly(α-lipoic acid) copolymer can be used as a biocompatible and stimuli-responsive nanocarrier for anticancer drug delivery, which may have potential clinical utility.
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