MXene-Based Nanosheets Reverse Tumor Hypoxia to Amplify Triple-Mode Cancer Therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• MXene exhibits promising biocompatibility and photothermal properties for cancer treatment.
• Challenges include poor stability in physiological environments and non-specific targeting, limiting its anti-tumor applications.
• Developing stable, targeted nanomaterials is crucial for effective cancer therapy.

Purpose of the Study:

• To design an efficient cascade catalytic system based on MXene for synergistic anti-cancer therapy.
• To enhance MXene's stability, targeting capability, and oxygen regeneration in the tumor microenvironment.
• To investigate the combined effects of starvation, gas, and photothermal therapies for improved cancer treatment.

Main Methods:

• MXene nanosheets were modified with folic acid and bovine serum albumin-coated manganese dioxide (MnO2) for improved dispersibility and targeting.
• Glucose oxidase (GOx) and L-arginine (L-Arg) were loaded onto the modified MXene to create a cascade catalytic system.
• The system was evaluated for its ability to perform photothermal therapy, starvation therapy (via GOx), and gas therapy (via L-Arg oxidation).
• MnO2 facilitated oxygen (O2) generation by decomposing hydrogen peroxide (H2O2), counteracting tumor hypoxia.

Main Results:

• The developed cascade catalytic system demonstrated enhanced dispersibility and active targeting of folate receptor-overexpressing tumors.
• The system effectively generated nitric oxide (NO) through the GOx/L-Arg pathway, inducing starvation and gas therapy.
• MnO2 mediated O2 generation, alleviating tumor hypoxia and enhancing therapeutic efficacy.
• In vivo and ex vivo experiments confirmed significant anti-cancer effects with low toxicity and side effects.

Conclusions:

• The MXene-based cascade catalytic system offers a novel, green, and promising strategy for cancer treatment.
• Synergistic starvation, gas, and photothermal therapies show superior anti-tumor efficacy compared to individual treatments.
• This approach overcomes MXene's limitations and presents a viable chemotherapeutic-free cancer therapy option.