Supramolecular Polymerization‐Induced Nanoassemblies for Self‐Augmented Cascade Chemotherapy and Chemodynamic Therapy of Tumor

• Published in: Angewandte Chemie International Edition 2021-08, Vol.60 (32), p.17570-17578
• Main Authors: Yang, Kuikun, Yu, Guocan, Yang, Zhiqing, Yue, Ludan, Zhang, Xiangjun, Sun, Chen, Wei, Jianwen, Rao, Lang, Chen, Xiaoyuan, Wang, Ruibing
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Antineoplastic Agents - toxicity; beta-Cyclodextrins - chemical synthesis; beta-Cyclodextrins - metabolism; beta-Cyclodextrins - therapeutic use; beta-Cyclodextrins - toxicity; Biocompatibility; Cell Line, Tumor; Chemotherapy; Cisplatin; Coordination Complexes - chemical synthesis; Coordination Complexes - metabolism; Coordination Complexes - therapeutic use; Coordination Complexes - toxicity; Cyclodextrins; Drug Carriers - chemical synthesis; Drug Carriers - metabolism; Drug Carriers - therapeutic use; Drug Carriers - toxicity; drug delivery; Drug Liberation; Female; Ferrous Compounds - chemical synthesis; Ferrous Compounds - metabolism; Ferrous Compounds - therapeutic use; Ferrous Compounds - toxicity; Free radicals; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hydroxyl Radical - metabolism; Hydroxyl radicals; Metallocenes - chemical synthesis; Metallocenes - metabolism; Metallocenes - therapeutic use; Metallocenes - toxicity; Mice; Mice, Inbred BALB C; Monomers; Nanomedicine - methods; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; Nanoparticles - therapeutic use; Nanoparticles - toxicity; Nanotechnology; Neoplasms - drug therapy; Platinum; Platinum - chemistry; Polymerization; Polymers - chemical synthesis; Polymers - metabolism; Polymers - therapeutic use; Polymers - toxicity; Prodrugs - chemistry; Prodrugs - metabolism; Prodrugs - therapeutic use; Prodrugs - toxicity; self-amplified dissociation; self-assembly; supramolecular polymerization; synergistic chemo/chemodynamic therapy; Toxicity; Tumors; β-Cyclodextrin
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202103721

The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2O2 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 H2O2 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 H2O2 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. We reported a one‐pot supramolecular polymerization‐induced self‐assembly approach to fabricate H2O2‐responsive nanomedicine with highly controllable drug loading and rapid clearance for self‐augmented synergistic chemo/chemodynamic cancer therapy.