Phagocytosis-Activating Nanocomplex Orchestrates Macrophage-Mediated Cancer Immunotherapy.

The phagocytosis of macrophages to tumor cells represents an alluring strategy for cancer immunotherapy; however, its effectiveness is largely hindered by the detrimental upregulation of anti-phagocytic signals and insufficient expression of pro-phagocytic signals of tumor cells. Here, a pro-phagocytic polymer-based nanocomplex is designed to promote the macrophage engulfment of tumor cells through concurrent modulation of both the "eat me" and "don't eat me" signals. The nanocomplex MNC is formed by complexing a synthetic PAMAM derivative (G4P-C7A) that is capable of intrinsically inducing the exposure of calreticulin (CALR, a crucial pro-phagocytic protein) and a small inference RNA that can inhibit the expression of CD47 (a primary anti-phagocytic protein).

A size-switchable nanocluster remodels the immunosuppressive microenvironment of tumor and tumor-draining lymph nodes for improved cancer immunotherapy.

Remodeling the immunosuppressive tumor microenvironment (TME) by immunomodulators has been well studied in the past years. However, strategies that enable concurrent modulation of both the immunosuppressive TME and tumor-draining lymph nodes (TDLNs) are still in the infancy. Here, we report a pH-sensitive size-switchable nanocluster, SPN-R848, to achieve simultaneous accumulation in tumor and TDLNs for immune activation.