Yang Kuikun, Yu Guocan, Yang Zhiqing, Yue Ludan, Zhang Xiangjun, Sun Chen, Wei Jianwen, Rao Lang, Chen Xiaoyuan, Wang Ruibing
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Avenida da Universidade, Taipa, Macau, China.
MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida da Universidade, Taipa, Macau, China.
Angew Chem Int Ed Engl. 2021 Aug 2;60(32):17570-17578. doi: 10.1002/anie.202103721. Epub 2021 Jun 27.
The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H O level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified β-cyclodextrin-ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H O in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H O in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self-augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.
肿瘤组织中细胞内过氧化氢水平不足阻碍了化学动力学疗法的临床应用。在此，我们通过一个简单的一步超分子聚合诱导自组装过程，使用铂（IV）配合物修饰的β-环糊精-二茂铁共轭物作为超分子单体，开发了一种超分子纳米颗粒。该超分子纳米颗粒在肿瘤中暴露于内源性过氧化氢时会迅速解离，原位释放羟基自由基以及铂（IV）前药，铂（IV）前药被还原为顺铂，从而显著促进肿瘤组织中过氧化氢的生成。因此，这种超分子纳米药物通过自我增强的级联自由基生成和药物释放克服了传统化学动力学疗法的局限性。此外，解离的超分子纳米颗粒可以通过肾脏清除轻易地从体内排出，有效避免全身毒性，并确保纳米药物的长期生物相容性。这项工作可能为用于级联化学/化学动力学疗法的新型超分子纳米组装体的设计和开发提供新的见解。
