A pH/STEAP Cascade-Responsive Nanomedicine with Self-Supplied Peroxide for Precise Chemodynamic Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Chemodynamic therapy (CDT) shows promise for cancer treatment but lacks selectivity.
• Self-supply of peroxide compounds can enhance CDT efficacy.
• Current peroxide-supplementing agents struggle to differentiate between cancerous and normal cells.

Purpose of the Study:

• To develop an intelligent nanomedicine for specific and efficient cancer treatment.
• To create a peroxide self-supplying chemodynamic agent with enhanced selectivity.
• To leverage endogenous cancer cell mechanisms for targeted therapy.

Main Methods:

• Development of amorphous iron oxide nanoparticles loaded with methyl linoleate hydroperoxide (AIO@MLH NPs).
• Investigation of nanomedicine endocytosis and decomposition in acidic endo/lysosomes.
• Exploration of the role of six-transmembrane epithelial antigen of the prostate (STEAP) in Fenton-type reactions and free radical generation.

Main Results:

• AIO@MLH NPs release MLH and Fe3+ upon endocytosis, with Fe3+ reduced to Fe2+ by STEAP.
• The Fe2+-MLH interaction generates free radicals, causing endo/lysosomal damage and cancer cell apoptosis.
• AIO@MLH NPs demonstrated potent cytotoxicity towards cancer cells, not normal cells, due to STEAP overexpression in tumors.

Conclusions:

• The developed nanomedicine exhibits cascade-responsive and peroxide self-supplying properties for precise cancer therapy.
• Endogenous STEAP is effectively utilized to improve the selectivity of peroxide self-supplying chemodynamic agents.
• This approach offers a promising strategy for developing precision medicine for cancer treatment.