An ATPase-Mimicking MXene nanozyme pharmacologically breaks the ironclad defense system for ferroptosis cancer...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Ferroptosis therapy faces challenges due to intracellular anti-ferroptotic signals.
• Cancer cells possess defense mechanisms, like the Nrf2 program, that confer resistance to ferroptosis.

Purpose of the Study:

• To develop a novel nanozyme-based strategy to overcome ferroptosis resistance in cancer therapy.
• To investigate the potential of vanadium carbide MXene nanozymes (PVCMs) in modulating the Nrf2 pathway.

Main Methods:

• Utilized vanadium carbide MXene nanozymes (PVCMs) with intrinsic ATPase-mimicking activity.
• Investigated the catalytic dephosphorylation of ATP to ADP by PVCMs.
• Explored the cascade mechanism triggered by altered cellular energy status and glutathione depletion.

Main Results:

• PVCMs demonstrated high ATPase-like activity, selectively converting ATP to ADP.
• PVCMs effectively inhibited the Nrf2 program, a master anti-ferroptotic mediator.
• This inhibition led to selective ferroptosis induction in triple-negative breast cancer (TNBC) cells.

Conclusions:

• PVCMs can pharmacologically modulate the Nrf2 pathway by mimicking ATPase activity.
• This nanozyme-based approach offers a new strategy to overcome ferroptosis resistance in TNBC.
• The study presents a paradigm for using active nanozymes to target cellular signaling for therapeutic benefit.