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

Abstract

Macrophages are vital regulators of the host defense in organisms. In response to different local microenvironments, resting macrophages (M0) can be polarized into different phenotypes, pro-inflammatory (M1) or anti-inflammatory (M2), and perform different roles in different physiological or pathological conditions. Polarized macrophages can also be further reprogrammed by reversing their phenotype according to the changed milieu. Macrophage polarization and reprogramming play essential roles in maintaining the steady state of the immune system and are involved in the processes of many diseases. As foreign substances, nanoparticles (NPs) mainly target macrophages after entering the body. NPs can perturb the polarization and reprogramming of macrophages, affect their immunological function and, therefore, affect the pathological process of disease. Optimally-designed NPs for the modulation of macrophage polarization and reprogramming might provide new solutions for treating diseases. Systematically investigating how NPs affect macrophage polarization is crucial for understanding the regulatory effects of NPs on immune cells in vivo. In this review, macrophage polarization by NPs is summarized and discussed.

Keywords: macrophage; nanoparticles; polarization; reprogramming.

Figure 1

Signaling pathways of macrophage polarization. IRF, STAT, NF-κB, and suppressor of cytokine signaling (SOCS) are the major pathways of macrophage polarization. Krüppel-like factor 4 (KLF-4) is the downstream protein of STAT6. GO (graphene oxide) could induce macrophage polarization towards M1 phenotype [45]. Plasmid DNA expressing IL-10 or IL-4 encapsulated hyaluronic acid-poly (ethyleneimine) NPs (HA-PEI/pDNA-IL-10 or HA-PEI/pDNA-IL-4 NPs) [46] and tuftsin-modified alginate NPs containing murine cytokine IL-10 plasmid DNA [34] modulated macrophage reprogramming from M1 toward M2 (red arrow).