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

Kuikun Yang; Guocan Yu; Zhiqing Yang; Ludan Yue; Xiangjun Zhang; Chen Sun; Jianwen Wei; Lang Rao; Xiaoyuan Chen; Ruibing Wang

doi:10.1002/anie.202103721

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

Angew Chem Int Ed Engl. 2021 Aug 2;60(32):17570-17578. doi: 10.1002/anie.202103721. Epub 2021 Jun 27.

Authors

Kuikun Yang^{1

2}, Guocan Yu³, Zhiqing Yang^{1

2}, Ludan Yue^{1

2}, Xiangjun Zhang^{1

2}, Chen Sun^{1

2}, Jianwen Wei^{1

2}, Lang Rao⁴, Xiaoyuan Chen^{5

6

7}, Ruibing Wang^{1

2}

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Avenida da Universidade, Taipa, Macau, China.
² MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida da Universidade, Taipa, Macau, China.
³ Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, China.
⁴ Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, China.
⁵ Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, Singapore.
⁶ Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁷ Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

PMID: 34041833
DOI: 10.1002/anie.202103721

Abstract

The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H₂ O₂ 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 H₂ O₂ 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 H₂ O₂ 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.

Keywords: drug delivery; self-amplified dissociation; self-assembly; supramolecular polymerization; synergistic chemo/chemodynamic therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / metabolism
Antineoplastic Agents / therapeutic use*
Antineoplastic Agents / toxicity
Cell Line, Tumor
Coordination Complexes / chemical synthesis
Coordination Complexes / metabolism
Coordination Complexes / therapeutic use
Coordination Complexes / toxicity
Drug Carriers / chemical synthesis
Drug Carriers / metabolism
Drug Carriers / therapeutic use*
Drug Carriers / toxicity
Drug Liberation
Female
Ferrous Compounds / chemical synthesis
Ferrous Compounds / metabolism
Ferrous Compounds / therapeutic use
Ferrous Compounds / toxicity
Hydrogen Peroxide / metabolism
Hydroxyl Radical / metabolism
Metallocenes / chemical synthesis
Metallocenes / metabolism
Metallocenes / therapeutic use
Metallocenes / toxicity
Mice
Mice, Inbred BALB C
Nanomedicine / methods
Nanoparticles / chemistry
Nanoparticles / metabolism
Nanoparticles / therapeutic use*
Nanoparticles / toxicity
Neoplasms / drug therapy*
Platinum / chemistry
Polymerization
Polymers / chemical synthesis
Polymers / metabolism
Polymers / therapeutic use*
Polymers / toxicity
Prodrugs / chemistry
Prodrugs / metabolism
Prodrugs / therapeutic use
Prodrugs / toxicity
beta-Cyclodextrins / chemical synthesis
beta-Cyclodextrins / metabolism
beta-Cyclodextrins / therapeutic use
beta-Cyclodextrins / toxicity

Substances

Antineoplastic Agents
Coordination Complexes
Drug Carriers
Ferrous Compounds
Metallocenes
Polymers
Prodrugs
beta-Cyclodextrins
Hydroxyl Radical
Platinum
Hydrogen Peroxide
ferrocene