School of Pharmacy, Shenyang Pharmaceutical University, Shenhe District, Shenyang, China.
School of Material Science and Engineering, Northeast University, Heping District, Shenyang, China.
J Biomater Sci Polym Ed. 2020 Oct;31(15):2007-2023. doi: 10.1080/09205063.2020.1792046. Epub 2020 Jul 20.
Acidic tumor microenvironment has been extensively explored to design pH-responsive paclitaxel prodrug micelles for cancer therapy. The object of this study is to investigate the pH-responsive drug release behavior and the anti-proliferation capacity of acetal-linked paclitaxel polymeric prodrug micelles. The prodrug was synthesized and evaluated for paclitaxel content. The prodrug micelles were fabricated and characterized for morphology, size, pH-responsive paclitaxel release, cellular uptake, and anti-proliferation. Paclitaxel content was 33 wt%. The prodrug micelles exhibited spherical structure with the hydrodynamic diameter of 154 nm. Besides, the paclitaxel release behavior was verified to be pH-responsive, and 77%, 38%, and 17% of parent free paclitaxel was released from the nano-sized prodrug micelles in 13 h at pH 5.5, 6.5, and 7.4, respectively. The cellular uptake assessment demonstrated the time-dependent internalization of prodrug micelles. Meanwhile, CCK-8 analysis showed that prodrug micelles possessed the potent anti-proliferation effects. Prodrug micelles based on aliphatic polycarbonates present a promising platform for cancer chemotherapy due to the pH-responsive characteristics of acetal bond, potent anti-proliferation effects, and outstanding cytocompatibility of aliphatic polycarbonates.
酸性肿瘤微环境已被广泛探索，用于设计 pH 响应型紫杉醇前药胶束用于癌症治疗。本研究的目的是研究腙键连接的紫杉醇聚合物前药胶束的 pH 响应性药物释放行为和抗增殖能力。合成前药并评估紫杉醇含量。制备前药胶束并对形态、粒径、pH 响应性紫杉醇释放、细胞摄取和抗增殖进行了表征。紫杉醇含量为 33wt%。前药胶束表现出球形结构，水动力直径为 154nm。此外，证实了紫杉醇的释放行为是 pH 响应的，在 13 小时内，在 pH 值为 5.5、6.5 和 7.4 时，从纳米级前药胶束中分别释放出 77%、38%和 17%的游离紫杉醇母体药物。细胞摄取评估表明前药胶束具有时间依赖性内化作用。同时，CCK-8 分析表明前药胶束具有很强的抗增殖作用。基于脂肪族聚碳酸酯的前药胶束由于腙键的 pH 响应特性、强大的抗增殖作用和脂肪族聚碳酸酯出色的细胞相容性，为癌症化疗提供了一个有前途的平台。
