Nano-enabled photosynthesis in tumours to activate lipid peroxidation for overcoming cancer resistances

Area of Science:

• Oncology
• Nanotechnology
• Biomedical Engineering

Background:

• Apoptosis dysregulation contributes to intrinsic and acquired melanoma resistance.
• There is a need for oncological treatments that activate nonapoptotic cell death pathways.

Purpose of the Study:

• To develop nano-enabled photosynthesis to induce ferroptosis and overcome melanoma resistance.
• To investigate the efficacy of combining photosynthetic microcapsules (PMCs) with X-rays in treating melanoma.

Main Methods:

• Photosynthetic microcapsules (PMCs) were engineered by encapsulating cyanobacteria and upconversion nanoparticles in alginate.
• PMCs were activated by near-infrared photons to create a hyperoxic tumor microenvironment.
• The combined treatment of PMCs and X-rays was applied to melanoma cells and xenografts.

Main Results:

• The combination therapy induced lipid peroxidation, Fe2+ release, and ferroptosis in melanoma.
• This approach effectively suppressed glutathione peroxidase 4 and reduced glutathione levels.
• The treatment overcame both intrinsic and acquired melanoma resistance, inhibited metastasis, and improved survival rates in mice.

Conclusions:

• Nano-enabled photosynthesis offers a promising strategy to activate ferroptosis and overcome melanoma resistance.
• This approach represents a novel avenue for developing advanced oncological treatments.
• The developed PMCs can be utilized to trigger nonapoptotic cell death pathways in tumors.