Immune modulating nanoparticles depleting tumor-associated macrophages to enhance immune checkpoint blockade therapy

Targeting the tumor-associated macrophages (TAMs) with combinational drugs is a promising strategy to improve immune checkpoint blocking therapies. To optimize the synergetic effect of TAM-depletion, it is required for the delivery system to deliver multiple therapeutic drugs to their corresponding action-sites. Herein, we design an immune modulating nanoparticle (IMNP) that can achieve a spatial control of the release sites of the drugs to synergistically deplete TAMs. IMNP has a core-shell structure in which the shell disassembles in acidic tumor microenvironment, resulting in the release of bindarit into the intercellular space to inhibit the recruitment of monocytes and exposing the core nCS(ALN)-Man to trigger the apoptosis of TAMs. With this unique feature, systemic administration of IMNP to tumor-bearing mice effectively eliminated TAMs and altered the immunosuppressing tumor environment, which significantly improved the anti-tumor efficacy of anti-PD-1. Considering the antitumor efficacy of chemotherapy, irradiation and vascular-targeted therapies is also coun-teracted by TAMs, IMNP could be further developed in combination with these therapies for cancer treatment, implying the potential as a general application to improve the efficacy of cancer therapies.