Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China.
Institute of Biomedical Materials and Engineering, College of Chemistry and Chemical Engineering, College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China; Laboratory for New Fiber Materials and Modern Textile, Growing Base for State Key Laboratory, Qingdao University, Qingdao 266071, China.
J Control Release. 2021 Dec 10;340:102-113. doi: 10.1016/j.jconrel.2021.10.027. Epub 2021 Oct 28.
Traditional and single treatment strategies are difficult to achieve good results due to tumor resistance and complex mechanisms. Combination therapy through co-delivery systems is one of the methods to improve the effectiveness of cancer treatment. The polyprodrug platform has inherent advantages such as high drug loading and strong stability. Herein, a new reactive oxygen species (ROS)-responsive micelle composed of poly 10-hydroxycamptothecin (pHCPT) and PEG is reported, which loaded dexamethasone (DEX) as synergistic drugs. The micelles collapse in the complex microenvironment of tumor cells to release DEX. The first released DEX can increase the ROS level of tumor cells, thereby facilitating the cleavage of thioketal bonds to release intact HCPT molecules. Meanwhile, DEX can normalize tumor blood vessels, reduce adverse reactions, and further improve the efficacy of HCPT. This co-delivery system shows an ideal tumor suppressive effect in vivo and in vitro. Designing drugs into a modular multi-drug platform and selecting appropriate synergistic drugs according to the treatment plan provides a convenient strategy for future clinical treatment.
由于肿瘤耐药性和复杂的机制，传统的单一治疗策略难以取得良好的效果。通过联合递送系统的联合治疗是提高癌症治疗效果的方法之一。前药平台具有载药率高、稳定性强等固有优势。本文报道了一种由聚 10-羟基喜树碱（pHCPT）和 PEG 组成的新型活性氧（ROS）响应胶束，负载地塞米松（DEX）作为协同药物。胶束在肿瘤细胞的复杂微环境中坍塌，释放 DEX。首先释放的 DEX 可以增加肿瘤细胞的 ROS 水平，从而促进硫缩酮键的断裂，释放完整的 HCPT 分子。同时，DEX 可以使肿瘤血管正常化，减少不良反应，进一步提高 HCPT 的疗效。该共递药系统在体内和体外均表现出理想的肿瘤抑制作用。将药物设计成模块化的多药物平台，并根据治疗方案选择合适的协同药物，为未来的临床治疗提供了一种便捷的策略。
