Biodegradable Nanocatalyst with Self-Supplying Fenton-like Ions and H2O2 for Catalytic Cascade-Amplified Tumor Therapy.

Abstract

Therapeutic nanosystems triggered by a specific tumor microenvironment (TME) offer excellent safety and selectivity in the treatment of cancer by in situ conversion of a less toxic substance into effective anticarcinogens. However, the inherent antioxidant systems, hypoxic environment, and insufficient hydrogen peroxide (H2O2) 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 (MnO2) 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 MnO2 depletes glutathione (GSH) to destroy the reactive oxygen defensive mechanisms and achieves continuous oxygen generation, thus enhancing the catalytic efficiency of GOD to burst H2O2. Benefiting from the chelation reaction between the released Cu2+ 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 Mn2+ can initiate magnetic resonance imaging signals for the tracking of the nanocatalyst.

• Authors: Wenting Li, Xinglu Zhou, Shikai Liu, Jialing Zhou, He Ding, Shili Gai, Rumin Li, Lei Zhong, Huijie Jiang, Piaoping Yang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 13 Issue 43 Pg. 50760-50773 (Nov 03 2021) ISSN: 1944-8252 [Electronic] United States
• PMID: 34672620 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Ions
• Manganese Compounds
• Oxides
• Zeolites
• Copper
• Hydrogen Peroxide
• Glucose Oxidase
• manganese dioxide
• Disulfiram

Topics

• Antineoplastic Agents (chemistry, metabolism, pharmacology)
• Catalysis
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Copper (chemistry, metabolism, pharmacology)
• Disulfiram (chemistry, metabolism, pharmacology)
• Drug Screening Assays, Antitumor
• Glucose Oxidase (chemistry, metabolism)
• HeLa Cells
• Humans
• Hydrogen Peroxide (chemistry, metabolism, pharmacology)
• Ions (chemistry, metabolism, pharmacology)
• Manganese Compounds (chemistry, metabolism, pharmacology)
• Molecular Structure
• Oxides (chemistry, metabolism, pharmacology)
• Particle Size
• Zeolites (chemistry, metabolism, pharmacology)