Liu Jiahui, Tang Menghuan, Zhou Yanghao, Long Yijuan, Cheng Yuan, Zheng Huzhi
Key Laboratory of Luminescent and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University Chongqing 400715 P. R. China
Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 P. R. China.
RSC Adv. 2020 Feb 14;10(12):6919-6926. doi: 10.1039/c9ra09923a. eCollection 2020 Feb 13.
Cancer is the leading cause of death and the most important obstacle to increasing life expectancy. With the sophisticated design and research of anticancer drugs, multidrug resistance to chemotherapy has become more and more common. After the emergence of multidrug resistance, the development of a new drug is beset with difficulties. The repurposing of non-anticancer drugs is thus a timely strategy for cancer therapy. Here, we highlight the potential of repurposing siramesine, a central nervous system drug for antitumor research and we construct a metal organic framework-based nanoplatform for effective intracellular accumulation and pH-response siramesine release. The released drug induces lysosome membrane permeabilization, leading to lysosomal cathepsins leakage and then results in cell apoptosis. Due to the modification of folic acids, the constructed drug delivery nanosystem shows good biocompatibility and efficient cancer cell targeting. Importantly, the drug delivery system shows enhanced anticancer efficacy , which not only effectively kills cancer cells but also kills multidrug resistant cells. Thus, the drug delivery nanosystem constructed in this study is thought to become a promising anticancer agent for cancer therapy and even overcoming multidrug resistance, which provides good prospects for biomedical applications.
癌症是主要的死亡原因，也是延长预期寿命的最重要障碍。随着抗癌药物的精密设计与研究，化疗的多药耐药性变得越来越普遍。多药耐药性出现后，新药研发困难重重。因此，将非抗癌药物重新用于癌症治疗是一种适时的策略。在此，我们强调将中枢神经系统药物西拉米辛重新用于抗肿瘤研究的潜力，并构建了一种基于金属有机框架的纳米平台，用于实现有效的细胞内积累和pH响应性西拉米辛释放。释放的药物诱导溶酶体膜通透性增加，导致溶酶体组织蛋白酶泄漏，进而导致细胞凋亡。由于叶酸修饰，构建的药物递送纳米系统表现出良好的生物相容性和高效的癌细胞靶向性。重要的是，该药物递送系统显示出增强的抗癌功效，不仅能有效杀死癌细胞，还能杀死多药耐药细胞。因此，本研究构建的药物递送纳米系统有望成为一种有前途的抗癌药物，用于癌症治疗甚至克服多药耐药性，为生物医学应用提供了良好前景。
