College of Chemistry, Jilin University, Changchun 130012, PR China.
College of Resources and Environment, Jilin Agricultural University, Changchun 130118, PR China.
Int J Biol Macromol. 2023 Dec 1;252:126424. doi: 10.1016/j.ijbiomac.2023.126424. Epub 2023 Aug 20.
Controlled and accurate drug release at the target site have been the focus of research. Especially in cancer therapy, economical, convenient and accurate delivery strategies could help to reduce the toxic effects of drugs on normal tissues and improve drug availability. In the study, glutathione (GSH)-responsive microcapsules (FA-RSMCs) were prepared by sonochemical method based on thiolated modified starch. 10-Hydroxycamptothecin (HCPT) was designed as a reactive oxygen species (ROS)-responsive polyprodrug (polyHCPT), which was loaded into the core of the microcapsules to obtain stepwise released drug delivery carriers. In the tumor microenvironment, FA-RSMCs first triggered GSH-responsive cleavage to release polyHCPT, followed by ROS-responsive cleavage of polyHCPT to release intact HCPT drug molecules. The results of experiments in simulated tumor microenvironment showed that FA-RSMCs exhibited good cascade-response release properties in vitro. It exhibited good anti-tumor ability and protection of normal cells in cytotoxicity in vitro. This strategy enhanced the accuracy and safety of targeted delivery of HCPT via microcapsules, which has potential for clinical application.
在靶部位进行控制和精确的药物释放一直是研究的重点。特别是在癌症治疗中，经济、方便和准确的递药策略有助于降低药物对正常组织的毒性作用，并提高药物的有效性。本研究采用超声化学法，以巯基化修饰淀粉为原料制备了谷胱甘肽（GSH）响应性微胶囊（FA-RSMCs）。10-羟基喜树碱（HCPT）被设计为活性氧（ROS）响应性多前药（polyHCPT），其被装载到微胶囊的核心中，以获得逐步释放的药物递送载体。在肿瘤微环境中，FA-RSMCs 首先触发 GSH 响应性断裂以释放 polyHCPT，然后 polyHCPT 发生 ROS 响应性断裂以释放完整的 HCPT 药物分子。模拟肿瘤微环境中的实验结果表明，FA-RSMCs 在体外具有良好的级联响应释放特性。其在体外细胞毒性中表现出良好的抗肿瘤能力和对正常细胞的保护作用。该策略通过微胶囊增强了 HCPT 靶向递送的准确性和安全性，具有临床应用的潜力。
