Zhao Ziwei, Yao Xuemei, Zhang Zhe, Chen Li, He Chaoliang, Chen Xuesi
Department of Chemistry, Northeast Normal University, Changchun, 130024, P. R. China.
Macromol Biosci. 2014 Nov;14(11):1609-18. doi: 10.1002/mabi.201400251. Epub 2014 Aug 21.
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.
在此，制备了基于两亲性葡聚糖-嵌段-聚丙交酯（Dex-b-PLA）的3-羧基-5-硝基苯硼酸（CNPBA）壳交联胶束，并将其用于高效的细胞内药物递送。由于与二醇形成硼酸酯的过程具有可逆的pH依赖性，经CNPBA修饰的Dex-b-PLA表现出优异的pH敏感性。在中性水性条件下，CNPBA-Dex-b-PLA形成壳交联胶束以实现阿霉素（DOX）负载，而在酸性条件下，硼酸酯水解且胶束去交联以释放负载的DOX。体外释放研究表明，DOX货物在生理条件下的释放最小化，而在低pH值下会出现突释。通过MTT法研究的CNPBA-Dex-b-PLA的细胞活力超过90%，表明作为一种药物递送系统，CNPBA-Dex-b-PLA具有良好的细胞相容性。这些特性表明，pH响应性可生物降解的CNPBA-Dex-b-PLA能够有效地将DOX负载并递送至肿瘤细胞，并在体外增强对细胞增殖的抑制作用，为癌症治疗提供了一个良好的药物递送系统平台。
