Boronic acid shell-crosslinked dextran-b-PLA micelles for acid-responsive drug delivery.
Boronic acid shell-crosslinked dextran-b-PLA micelles for acid-responsive drug delivery.
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DOI：
10.1002/mabi.201400251
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发表时间：
2014-11
影响因子：
4.6
通讯作者：
Ziwei S. Zhao;Xuemei Yao;Zhe Zhang;Li Chen;Chaoliang He;Xuesi Chen
中科院分区：
文献类型：
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作者：
Ziwei S. Zhao;Xuemei Yao;Zhe Zhang;Li Chen;Chaoliang He;Xuesi Chen
本文制备了基于两亲性葡聚糖-嵌段-聚乳酸（Dex-b-PLA）的3-羧基-5-硝基苯基硼酸（CNPBA）壳交联胶束并用于有效的细胞内药物递送。由于与二醇可逆的pH依赖性结合以形成硼酸酯，CNPBA修饰的Dex-b-PLA显示出优异的pH敏感性。在中性水性条件下，CNPBA-Dex-b-PLA形成壳交联的胶束以实现DOX负载，而在酸性条件下，硼酸酯水解并且胶束去交联以释放负载的DOX。体外释放研究表明，DOX货物的释放在生理条件下最小化，而在低pH值下则会出现爆发式释放。MTT法检测CNPBA-Dex-b-PLA的细胞活力大于90%，表明CNPBA-Dex-b-PLA作为药物释放系统具有良好的细胞相容性。这些特征表明，pH响应性可生物降解的CNPBA-Dex-b-PLA可以有效地将DOX负载并递送到肿瘤细胞中，并增强体外细胞增殖的抑制，为癌症治疗的药物递送系统提供了有利的平台。
Herein, 3-carboxy-5-nitrophenylboronic acid (CNPBA) shell-crosslinked micelles based on amphiphilic dextran-block-polylactide (Dex-b-PLA) are prepared and used for efficient intracellular drug deliveries. Due to the reversible pH-dependent binding with diols to form boronate esters, CNPBA modified Dex-b-PLA shows excellent pH-sensitivity. In neutral aqueous conditions, CNPBA-Dex-b-PLA forms shell-crosslinked micelles to enable DOX loading, while in acid conditions, the boronate esters hydrolyze and the micelles de-crosslink to release loaded DOX. In vitro release studies indicate that the release of the DOX cargo is minimized at physiological conditions, while there is a burst release in response to low pHs. The cell viability of CNPBA-Dex-b-PLA investigated by MTT assay was more than 90%, indicating that, as a drug delivery system, CNPBA-Dex-b-PLA has good cytocompatibility. These features suggest that the pH-responsive biodegradable CNPBA-Dex-b-PLA can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform as a drug delivery system for cancer therapy.