A Metal-Organic Framework-Based Immune-Regulating Nanocarrier Depot for Enhanced Combination Cancer Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Immunotherapy shows promise in cancer treatment but faces limitations due to the immunosuppressive tumor microenvironment.
• Low response rates in many cancers highlight the need for strategies to overcome tumor-induced immune suppression.

Purpose of the Study:

• To develop an iron-based nanoscale metal-organic framework (MOF) as a drug carrier with immune-stimulating activity.
• To reprogram the tumor microenvironment and enhance anti-tumor immunity.

Main Methods:

• Synthesized a modified MOF (rMOF-MA) from NH2-MIL-88B, enhancing reactive oxygen species production and promoting M1 macrophage polarization.
• Loaded the MOF with resiquimod (R848) and encapsulated it in a hydrogel to create a local inflammatory niche.
• Combined the hydrogel-based immunotherapy with immune checkpoint blockade (ICB) therapy.

Main Results:

• The rMOF-MA effectively promoted macrophage polarization towards a pro-inflammatory M1 phenotype.
• The hydrogel-based combination immunotherapy significantly inhibited tumor growth, lung metastasis, and post-surgical tumor recurrence.
• Enhanced systemic anti-tumor immunity was observed.

Conclusions:

• The developed MOF-based immune-regulating depot shows significant potential for clinical cancer immunotherapy.
• This approach offers a promising strategy to overcome the limitations of current immunotherapies by modulating the tumor microenvironment.