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一种 pH 响应性壳聚糖-b-聚(对二氧环己酮)纳米载体:形成及高效抗肿瘤药物递送。

A pH-responsive chitosan-b-poly(p-dioxanone) nanocarrier: formation and efficient antitumor drug delivery.

机构信息

Center for Degradable and Flame-Retardant Polymeric Materials (ERCPM-MoE), College of Chemistry, State Key Laboratory of Polymer Materials Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, People's Republic of China.

出版信息

Nanotechnology. 2013 Apr 12;24(14):145101. doi: 10.1088/0957-4484/24/14/145101. Epub 2013 Mar 12.

Abstract

Increasing attention has recently been paid to the fabrication of drug delivery systems with excellent cell internalization and intracellular drug release properties. In this study, an amphiphilic block copolymer of chitosan was synthesized for the first time, which can self-assemble into micelles in a neutral aqueous solution but partially disassemble in an acidic endosomal/lysosomal environment. The antitumor drug, camptothecin (CPT), was encapsulated in the cores of the micelles for tumor cell therapy. In vitro drug release studies demonstrated that the micelles presented a much faster release of CPT at pH 5.0 than at pH 7.4. Blank micelles were found to be nontoxic in preliminary in vitro cytotoxicity assays. Cell experiments showed that the CPT-loaded micelles could be effectively internalized by Hela cells and accomplished a potent antitumor cell efficacy, indicating that the chitosan-based micelles might be an attractive new platform for efficient intracellular drug delivery.

摘要

最近,人们越来越关注制备具有优异细胞内化和细胞内药物释放性能的药物传递系统。在本研究中,首次合成了一种具有两亲性的壳聚糖嵌段共聚物,该共聚物在中性水溶液中可以自组装成胶束,但在酸性内涵体/溶酶体环境中会部分解组装。将抗肿瘤药物喜树碱(CPT)包封在胶束的核心中,用于肿瘤细胞治疗。体外药物释放研究表明,胶束在 pH5.0 时比在 pH7.4 时释放 CPT 的速度要快得多。空白胶束在初步体外细胞毒性试验中被发现没有毒性。细胞实验表明,载有 CPT 的胶束可以被 Hela 细胞有效内化,并具有强大的抗肿瘤细胞功效,这表明基于壳聚糖的胶束可能是一种有吸引力的新的高效细胞内药物传递平台。

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