School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, P.R. China.
Drug Deliv. 2023 Dec;30(1):2219426. doi: 10.1080/10717544.2023.2219426.
Doxorubicin (DOX) is a commonly studied chemotherapeutic agent for the treatment of solid tumors, but the severe side effects limit its clinical application. It is shown that DOX-metal chelate has lower cytotoxicity compared with DOX, as the anthracyclines of DOX can form coordinative interaction with transition metal ions. In addition, the transition metal ions could catalyze the production of hydroxyl radicals (·OH) via Fenton/Fenton-like reactions to achieve antitumor chemodynamic therapy (CDT). In this study, copper ions (Cu) were applied to obtain DOX/Cu(II) prodrug, and a liposomal formulation was used to avoid the rapid blood clearance and optimize the biodistribution of this prodrug. and antitumor results demonstrated that this pH sensitive Cu-chelating prodrug can reduce adverse effects of DOX but improve the antitumor efficiency due to the combination of chemotherapy and chemodynamic therapy. Our study provided a facile and effective approach of metal-chelating prodrug strategy for combination cancer therapy strategy.
阿霉素（DOX）是一种常用于治疗实体瘤的化疗药物，但严重的副作用限制了其临床应用。研究表明，与 DOX 相比，DOX-金属螯合物的细胞毒性更低，因为 DOX 的蒽环类药物可以与过渡金属离子形成配位相互作用。此外，过渡金属离子可以通过芬顿/类芬顿反应催化产生羟基自由基（·OH），从而实现肿瘤化学动力学治疗（CDT）。在本研究中，应用铜离子（Cu）获得 DOX/Cu（II）前药，并使用脂质体制剂避免前药的快速血液清除，优化其生物分布。抗肿瘤结果表明，这种 pH 敏感的 Cu 螯合前药可以降低 DOX 的不良反应，但由于化疗和化学动力学治疗的结合，提高了抗肿瘤效率。我们的研究为联合癌症治疗策略提供了一种简便有效的金属螯合前药策略。
