Drug Delivery ( IF 6.5 ) Pub Date : 2023-06-07 , DOI: 10.1080/10717544.2023.2219426 Wen Zhang 1 , Peng Zhang 1 , Xiaopeng Xu 1 , Minghui Li 1 , Shasha Wang 1 , Hongjie Mu 1 , Kaoxiang Sun 1
Abstract
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 in vitro 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 (Cu2+) 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. In vitro and in vivo 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.
中文翻译:
基于阿霉素的螯合物前药中铜离子对癌症化学-化学动力学联合治疗的协同作用
摘要
阿霉素(DOX)是一种常用的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。结果表明,与DOX相比,DOX-金属螯合物具有较低的体外细胞毒性,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/类芬顿反应催化羟基自由基(·OH)的产生,从而实现抗肿瘤化学动力学治疗(CDT)。在本研究中,应用铜离子(Cu 2+ )获得DOX/Cu(II)前药,并使用脂质体制剂来避免快速血液清除并优化该前药的生物分布。体外和体内抗肿瘤结果表明,这种pH敏感的铜螯合前药可以减少DOX的不良反应,同时由于化疗和化学动力学治疗的结合而提高抗肿瘤效率。我们的研究为癌症联合治疗策略提供了一种简便有效的金属螯合前药策略方法。