Photoactivatable immunostimulatory nanoengineered microalgae for boosting cascade-activated antitumor immunity

Area of Science:

• Biomedical Engineering
• Immunology
• Materials Science

Background:

• Tumor immunogenicity and the immunosuppressive tumor microenvironment (TME) limit cancer immunotherapy efficacy.
• Developing strategies to enhance anti-tumor immune responses is crucial.

Purpose of the Study:

• To develop a photoactivatable immunostimulator for enhanced cancer immunotherapy.
• To simultaneously increase tumor immunogenicity and remodel the immunosuppressive TME.

Main Methods:

• Nanoengineered microalgae (PCC@AuNP) were developed as a photoactivatable immunostimulator.
• Mechanism investigated involves photocatalytic hydrogen generation, photosynthetic oxygen production, and lactic acid depletion.
• In vivo studies assessed tumor eradication, systemic immunity, and biosafety.

Main Results:

• PCC@AuNP induced robust immunogenic cell death via endoplasmic reticulum stress and mitochondrial dysfunction.
• Photosynthetic oxygen and depleted lactic acid alleviated TME immunosuppression.
• Enhanced cytotoxic T lymphocyte activity, reduced immunosuppressive cells, and M2 to M1 macrophage repolarization were observed.
• PCC@AuNP eradicated primary tumors and elicited systemic antitumor immunity with no observable toxicity.

Conclusions:

• The PCC@AuNP platform effectively enhances tumor immunogenicity and remodels the TME.
• This approach offers a safe and effective cancer immunotherapy strategy.
• PCC@AuNP represents a pioneering cascade-augmented gas-driven immunotherapy with superior precision and biosafety.