MnO₂-Assisted Photosynthetic Bacteria Interfering with the Adenosine-A2AR Metabolic Pathway to Enhance Tumor...

Area of Science:

• Biomedical Engineering
• Immunology
• Materials Science

Background:

• Tumor hypoxia promotes immunosuppression via adenosine (Ado) and A2A receptors (A2AR).
• Adenosine A2A receptor (A2AR) signaling hinders anti-tumor immunity, particularly following immunogenic cell death (ICD).

Purpose of the Study:

• To develop a MnO2-assisted photosynthetic bacteria (PSB) biohybrid (MnO2@PSB) for enhanced photothermal immunotherapy.
• To investigate the interference of MnO2@PSB with the adenosine-A2AR metabolic pathway in tumors.

Main Methods:

• Conjugation of manganese dioxide (MnO2) nanoflowers onto photosynthetic bacteria (PSB) via carbodiimide reaction.
• Utilizing MnO2@PSB as a photothermal agent under 808 nm laser irradiation to induce tumor cell ICD.
• Leveraging MnO2 to catalyze hydrogen peroxide decomposition, alleviating tumor hypoxia and reducing adenosine production.

Main Results:

• MnO2@PSB treatment induced tumor cell immunogenic cell death (ICD).
• Alleviation of tumor hypoxia reduced adenosine production and A2AR expression, reversing the immunosuppressive microenvironment.
• Enhanced anti-tumor immune responses, prolonged survival, and inhibited tumor growth, recurrence, and metastasis in mouse models.

Conclusions:

• The MnO2@PSB biohybrid effectively enhances photothermal immunotherapy by targeting the adenosine-A2AR metabolic pathway.
• This approach offers a promising strategy for overcoming tumor immunosuppression and improving therapeutic outcomes.
• Regulating metabolic pathways presents a viable direction for advancing anti-tumor immunotherapy.