Targeting tumor-associated macrophages with mannosylated nanotherapeutics delivering TLR7/8 agonist enhances cancer immunotherapy

Mannose-decorated nanoparticles loading R848 effectively targeted tumor-associated macrophages and dendritic cells in a tumor model.

• Tumor-associated macrophages (TAMs) make up 50-80% of stromal cells in solid tumors, which are associated with high mortality and poor prognosis.
• Simultaneous targeting of TAMs and tumor-infiltrating dendritic cells (TIDCs) may enhance tumor immunity and restore immunosurveillance.
• The nanoparticles, Man-pD-PLGA-NP@R848, were designed to target TAMs and TIDCs through a specific receptor-mediated mechanism.
• Man-pD-PLGA-NP@R848 activated immune responses by releasing R848, which stimulated specific receptors involved in immune signaling.
• This treatment could reprogram TAMs into antitumoral forms, reduce blood vessel formation, and shift the tumor environment from immunosuppressive to immune-activating.
• In mice with tumors, the approach increased infiltration of immune cells and hindered tumor development.

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