Glycocalyx-Mimicking Nanoparticles for Stimulation and Polarization of Macrophages via Specific Interactions

Malignant tumors develop multiple mechanisms to impair and escape from antitumor immune responses, of which tumor-associated macrophages that often show immunosuppressive phenotype (M2), play a critical role in tumor-induced immunosuppression. Therefore, strategies that can reverse M2 phenotype and even enhance immune-stimulation function of macrophage would benefit tumor immunotherapy. In this paper, self-assembled glyco-nanoparticles (glyco-NPs), as artificial glycocalyx, have been found to be able to successfully induce the polarization of mouse primary peritoneal macrophages from M2 to inflammatory type (M1). The polarization change was evidenced by the decreased expression of cell surface signaling molecules CD206 and CD23, and the increased expression of CD86. Meanwhile, secretion of cytokines supported this polarization change as well. More importantly, this phenomenon is observed not only in vitro, but also in vivo. As far as we known, this is the first report about macrophage polarization being induced by synthetic nanomaterials. Moreover, preparation, characterization of these glyco-NPs and their interaction with the macrophages are also demonstrated.