Self-Assembled Nanoparticles from the Amphiphilic Prodrug of Resiquimod for Improved Cancer Immunotherapy

PLRS nanoparticles, approximately 35 nm in size, effectively repolarized macrophages from M2 to M1 in a breast cancer model.

• Tumor-associated macrophages (TAMs) typically adopt a M2-like phenotype that suppresses immune responses.
• Repolarization of TAMs from M2 to M1 may reshape the tumor immunosuppressive microenvironment.
• Self-assembled nanoparticles from a polymeric prodrug of resiquimod (R848) were developed to target TAMs.
• These nanoparticles efficiently promoted the maturation of antigen-presenting cells (APCs).
• PLRS nanoparticles led to significant tumor growth inhibition in the 4T1 orthotopic breast cancer model with reduced systemic side effects.
• Mechanistic studies indicated increased infiltration of cytotoxic T cells into the tumor following TAM repolarization.

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