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

Abstract

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.

The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research

“…For example, macrophage reprogramming from the M1 phenotype to the M2 phenotype can be used to treat chronic inflammatory diseases [36]. The phenotypic shift of M2 macrophages toward an M1 macrophage subtype is beneficial for the early phases of inflammation and cancer immunotherapy [37]. …”

“…Glycocalyx-mimicking NPs (glycol-NPs) were observed to reverse the M2 phenotype [37]. Glycol-NPs were self-assembled by three sugars, galactopyranoside (Gal), mannopyranoside (Man) and fucopyranoside (Fuc).…”

“…In contrast to Man and Gal, Fuc caused high expression of CD86 by interacting with specific mannose receptors (MR, CD206) on macrophages. In vivo, peritoneal macrophages from glycol-NP injected mice were also observed to secrete high levels of pro-inflammatory monocyte chemotactic protein 1 (MCP-1) and TNF-α, proof of the polarization switch from M2 to M1 [37]. Further study suggested these glycol-NPs could specifically interact with the receptors expressed on M2 and the receptor-mediated uptake process might induce the phenotypic shift [37].…”

Supramolecular Glyco‐nanoparticles Toward Immunological Applications

“…Our group and several others have achieved some of such mimics by using self‐assembled glyco‐containing macromolecules . Very recently, we reported that our glycocalyx‐mimicking nanoparticles (glyco‐NPs) were able to activate macrophages by turning the immunosuppressive subtype to the immunoresponsive ones, which brought forth a great potential of such glyco‐NPs in immunotherapy …”

Shape Effect of Glyco-Nanoparticles on Macrophage Cellular Uptake and Immune Response

“…11 In our previous work, we have shown that the spherical GNPs ( D n = 30–40 nm) obtained via a block copolymer self-assembly strategy were able to induce the polarization of mouse primary peritoneal macrophages from immunosuppressive phenotype to inflammatory type. 12 …”