"Three-in-One" Nanozyme Composite for Augmented Cascade Catalytic Tumor Therapy

Area of Science:

• Biomimetic chemistry
• Nanotechnology
• Cancer therapy

Background:

• Natural cascade reactions offer efficiency but are complex to mimic.
• Orderly assembly of enzymes for cascade reactions remains a significant challenge.
• Chemodynamic therapy (CDT) shows promise but requires efficient reactive oxygen species generation.

Purpose of the Study:

• To develop a single nanozyme with integrated catalytic functions for cascade reactions.
• To create a drug-free therapeutic agent for enhanced tumor treatment.
• To overcome the limitations of complex enzyme assembly and cross-talk in biomimetic systems.

Main Methods:

• Synthesized a single Au-Pt nanozyme anchored on Cu2O NPs and encapsulated in a metal-organic framework (MOF).
• Utilized the nanozyme's catalase-like, glucose oxidase-like, and peroxidase-like activities for cascade reactions.
• Incorporated Pluronic F127 for improved hydrophilicity and biocompatibility.
• Leveraged tumor microenvironment triggers (acidity, glutathione) for nanozyme activation.

Main Results:

• The single nanozyme successfully mimicked a three-step cascade reaction: O2 supply, H2O2 production, and •OH generation.
• The MOF encapsulation protected the nanozyme and responded to the tumor microenvironment for targeted drug release.
• The composite exhibited excellent photothermal conversion and Cu2+ ions enhanced CDT by consuming glutathione (GSH).
• The nanozyme demonstrated improved chemodynamic therapy efficacy for tumor treatment.

Conclusions:

• A novel single nanozyme platform was developed for drug-free, cascade catalytic chemodynamic therapy.
• The designed nanozyme effectively addressed challenges in enzyme assembly and cross-talk.
• This approach offers a promising strategy for augmented tumor therapy with minimized side effects.