Cisplatin crosslinked pH-sensitive nanoparticles for efficient delivery of doxorubicin

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• 作者：Mingqiang Li ; Zhaohui Tang ; Shixian Lv ; Wantong Song ; Hua Hong ; Xiabin Jing ; Yuanyuan Zhang ; Xuesi Chen
• 关键词：Drug delivery ; Chemotherapy ; Crosslinking ; Nanoparticle ; Polysaccharide ; Controlled drug release
• 刊名：Biomaterials
• 出版年：April, 2014
• 年：2014
• 卷：35
• 期：12
• 页码：3851-3864
• 全文大小：5311 K

文摘

pH responsive cisplatin prodrug crosslinked polysaccharide-based nanoparticles were developed from succinic acid decorated dextran (Dex-SA) for active loading and triggered intracellular release of doxorubicin (DOX). Nanoparticles with uniform size were formed spontaneously in aqueous medium via electrostatic interaction between anionic Dex-SA and cationic DOX, and subsequently transformed into crosslinked nanoparticles (CL-Nanoparticles) in situ by readily crosslinking the micelles via chelate interactions between the ionic polymeric carrier and the platinum (II) antitumor drug. This strategy eliminated the need of organic solvents and sophisticated processes in the drug loading procedure. The in聽vitro release studies showed that DOX was released from the CL-Nanoparticles in a controlled and pH-dependent manner. Furthermore, the pharmacokinetics and biodistribution investigations indicated that, as compared to the non-crosslinked nanoparticles (NCL-Nanoparticles) and free DOX, the CL-Nanoparticles significantly prolonged the blood circulation time of drug, decreased accumulation in the normal tissues and enriched drug into the tumors. As a consequence, the DOX-loaded CL-Nanoparticles exhibited enhanced therapeutic efficacy in tumor-bearing mice compared with the NCL-Nanoparticles and free DOX, which were further confirmed by the histological and immunohistochemical analyses. These cisplatin prodrug crosslinked polysaccharide nanoparticles proved to be a promising nanomedicine drug delivery system for tumor-targeted delivery of DOX.