Biodegradable Nanocatalyst with Self-Supplying Fenton-like Ions and H 2 O 2 for Catalytic Cascade-Amplified Tumor Therapy

• Published in: ACS applied materials & interfaces Vol. 13; no. 43; pp. 50760 - 50773
• Main Authors: Li, Wenting, Zhou, Xinglu, Liu, Shikai, Zhou, Jialing, Ding, He, Gai, Shili, Li, Rumin, Zhong, Lei, Jiang, Huijie, Yang, Piaoping
• Format: Journal Article
• Language: English
• Published: United States 03.11.2021
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Catalysis; Cell Proliferation - drug effects; Cell Survival - drug effects; Copper - chemistry; Copper - metabolism; Copper - pharmacology; Disulfiram - chemistry; Disulfiram - metabolism; Disulfiram - pharmacology; Drug Screening Assays, Antitumor; Glucose Oxidase - chemistry; Glucose Oxidase - metabolism; HeLa Cells; Humans; Hydrogen Peroxide - chemistry; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - pharmacology; Ions - chemistry; Ions - metabolism; Ions - pharmacology; Manganese Compounds - chemistry; Manganese Compounds - metabolism; Manganese Compounds - pharmacology; Molecular Structure; Oxides - chemistry; Oxides - metabolism; Oxides - pharmacology; Particle Size; Zeolites - chemistry; Zeolites - metabolism; Zeolites - pharmacology; nanocatalyst; disulfiram; chemotherapy; chemodynamic therapy; Cu/ZIF-8
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c14598

Therapeutic nanosystems triggered by a specific tumor microenvironment (TME) offer excellent safety and selectivity in the treatment of cancer by conversion of a less toxic substance into effective anticarcinogens. However, the inherent antioxidant systems, hypoxic environment, and insufficient hydrogen peroxide (H O ) in tumor cells severely limit their efficacy. Herein, a new strategy has been developed by loading the chemotherapy prodrug disulfiram (DSF) and coating glucose oxidase (GOD) on the surface of Cu/ZIF-8 nanospheres and finally encapsulating manganese dioxide (MnO ) nanoshells to achieve efficient DSF-based cancer chemotherapy and dual-enhanced chemodynamic therapy (CDT). In an acidic TME, the nanocatalyst can biodegrade rapidly and accelerate the release of internal active substances. The outer layer of MnO depletes glutathione (GSH) to destroy the reactive oxygen defensive mechanisms and achieves continuous oxygen generation, thus enhancing the catalytic efficiency of GOD to burst H O . Benefiting from the chelation reaction between the released Cu and DSF, a large amount of cytotoxic CuET products is generated, and the Cu are concurrently released, thereby achieving efficient chemotherapy and satisfactory CDT efficacy. Furthermore, the release of Mn can initiate magnetic resonance imaging signals for the tracking of the nanocatalyst.