Manganese-Enriched Zinc Peroxide Functional Nanoparticles for Potentiating Cancer Immunotherapy

Area of Science:

• Nanotechnology
• Immunology
• Oncology

Background:

• Current immunotherapies face limitations due to insufficient immune activation and immunosuppressive tumor microenvironments (TME).
• Developing novel strategies to overcome these barriers is crucial for enhancing cancer treatment efficacy.

Purpose of the Study:

• To develop tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy.
• To investigate the potential of MONPs in inducing immunogenic cell death (ICD) and activating the stimulator of the interferon gene (STING) pathway.

Main Methods:

• Designed and synthesized manganese-enriched zinc peroxide nanoparticles (MONPs) responsive to the acidic tumor microenvironment.
• Evaluated MONPs' ability to generate hydroxyl radicals (•OH) for ICD induction.
• Assessed Mn2+ activation of the STING pathway, cytokine secretion, T cell responses, and modulation of immunosuppressive cells (Tregs, M2 macrophages).

Main Results:

• MONPs effectively disassociated in acidic TME, generating •OH to induce cancer cell immunogenic death (ICD).
• Activated STING pathway, leading to increased type I interferon and inflammatory cytokine secretion, promoting T cell responses.
• Reduced regulatory T cells (Tregs) and polarized M2 macrophages to M1 phenotype, alleviating TME immunosuppression.
• Combination therapy with anti-PD-1 antibody demonstrated superior inhibition of tumor growth and prevention of lung metastasis.

Conclusions:

• MONPs represent a functional nanoparticle strategy for amplifying STING innate stimulation in cancer immunotherapy.
• This approach offers a promising synergistic strategy to enhance anti-tumor immune responses and overcome TME-mediated immunosuppression.