State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China.
Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, PR China.
Mater Sci Eng C Mater Biol Appl. 2020 Jan;106:110159. doi: 10.1016/j.msec.2019.110159. Epub 2019 Sep 3.
Stimuli-triggered drug delivery systems have been recognized as a crucial strategy to achieve on-demand drug release at the tumor for improving therapeutic efficacy. In this work, novel biocompatible and biodegradable reactive oxygen species (ROS)-responsive amino acid- based polymeric micelles were developed for tumor-specific drug release triggered by high ROS levels in cancer cells, which were composed of amphiphilic poly(aspartic acid) (PASP) derivatives (PASP-BSer) with phenylborate serine (BSer) side groups as the ROS-responsive unit. A series of PASP-BSer conjugates with different degree of substitution (DS) were synthesized, and their self-assembly and HO-responsive behaviors were investigated to optimize the structure of PASP-BSer. In vitro drug loading and release studies confirmed that the optimized PASP-BSer micelles could effectively encapsulate the model anticancer drug doxorubicin (Dox) and exhibit desirable HO-triggered release behaviors. More importantly, Dox-loaded PASP-BSer micelles showed high selective cytotoxicity against A549 cancer cells than L929 normal cells. Accordingly, PASP-BSer micelles have significant potential as on-demand drug carriers for anticancer therapy.
刺激响应型药物递送系统已被认为是在肿瘤部位实现按需药物释放的关键策略，可提高治疗效果。在这项工作中，开发了新型生物相容性和可生物降解的活性氧（ROS）响应型氨基酸基聚合物胶束，用于由癌细胞中高水平的 ROS 触发的肿瘤特异性药物释放，该胶束由两亲性聚（天冬氨酸）（PASP）衍生物（具有苯硼酸丝氨酸（BSer）侧基的 PASP-BSer）组成，作为 ROS 响应单元。合成了一系列具有不同取代度（DS）的 PASP-BSer 缀合物，并研究了它们的自组装和 HO 响应行为，以优化 PASP-BSer 的结构。体外载药和释放研究证实，优化的 PASP-BSer 胶束可以有效包载模型抗癌药物阿霉素（Dox），并表现出理想的 HO 触发释放行为。更重要的是，载 Dox 的 PASP-BSer 胶束对 A549 癌细胞的选择性细胞毒性高于 L929 正常细胞。因此，PASP-BSer 胶束作为用于癌症治疗的按需药物载体具有重要的应用潜力。
