Degradable Fe₃O₄-based nanocomposite for cascade reaction-enhanced anti-tumor therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Cascade catalytic therapy shows promise for cancer treatment by converting hydrogen peroxide (H2O2) into toxic hydroxyl radicals (•OH) via Fenton reactions.
• Glucose oxidase (GOx) catalyzes glucose oxidation, producing H2O2 and supporting starvation therapy, while also generating gluconic acid that acidifies the tumor microenvironment (TME).

Purpose of the Study:

• To design pH-responsive, biodegradable nanocomposites (Fe3O4/GOx-PLGA) for dual-enzyme cascade reactions in the TME.
• To leverage glucose oxidation and Fenton-like reactions for enhanced cancer therapy through oxidative stress.

Main Methods:

• Synthesis of Fe3O4/GOx-PLGA nanocomposites.
• Evaluation of cascade reactions: glucose oxidation by GOx and Fenton-like reaction by Fe3O4.
• Assessment of nanocomposite response to the acidic TME and its effect on degradation and catalytic activity.
• In vitro testing on HeLa cells to evaluate therapeutic efficacy and systemic toxicity.

Main Results:

• The nanocomposite effectively consumed intratumoral glucose, producing H2O2 for starvation therapy and subsequently generating •OH via Fenton-like reactions for chemodynamic therapy (CDT).
• Gluconic acid production amplified acidity, accelerating nanocomposite degradation and enhancing the Fe3O4-H2O2 reaction for improved CDT.
• Highly efficient tumor inhibition was observed in HeLa cells with minimal systemic toxicity.

Conclusions:

• The Fe3O4/GOx-PLGA nanocomposite demonstrates a promising cooperative cancer therapy strategy.
• This dual-enzyme cascade approach effectively targets tumors via starvation and chemodynamic therapy.
• The pH-responsive nature and enhanced catalytic activity offer a potential advancement in cancer treatment.