【摘 要】
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Prodrug nanoassemblies,which can refrain from large excipients,achieve higher drug loading and control drug release,have been placed as the priority in drug del
【机 构】
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Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China“,”School of C
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Prodrug nanoassemblies,which can refrain from large excipients,achieve higher drug loading and control drug release,have been placed as the priority in drug delivery system.Reasoning that glutathione (GSH) and reactive oxygen species (ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system,we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge iinoleic acid (LA) and docetaxel (DTX).This mono thioether-linked conjugates (DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients.The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue.Our studies demonstrated that the nanoassemblies had uniform particle size,high stability and fast release behavior.DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve (AUC).Compared with DTX solution,the redox dual-responsive nanoassemblies had comparable cytotoxic activity.Besides,the antitumor efficacy was evaluated in mice bearing 4T1 xenograft.It tued out this nanoassemblies could enhance anticancer efficacy by increasing the dose because of higher tolerance.Overall,these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.
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