Macrophage-Engineered Vesicles for Therapeutic Delivery and Bidirectional Reprogramming of Immune Cell Polarization

Abstract

Macrophages, one of the most important phagocytic cells of the immune system, are highly plastic and are known to exhibit diverse roles under different pathological conditions. The ability to repolarize macrophages from pro-inflammatory (M1) to anti-inflammatory (M2) or vice versa offers a promising therapeutic approach for treating various diseases such as traumatic injury and cancer. Herein, it is demonstrated that macrophage-engineered vesicles (MEVs) generated by disruption of macrophage cellular membranes can be used as nanocarriers capable of reprogramming macrophages and microglia toward either pro- or anti-inflammatory phenotypes. MEVs can be produced at high yields and easily loaded with diagnostic molecules or chemotherapeutics and delivered to both macrophages and cancer cells in vitro and in vivo. Overall, MEVs show promise as potential delivery vehicles for both therapeutics and their ability to controllably modulate macrophage/microglia inflammatory phenotypes.

Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity

“…Astrocyte‐conditioned media (ACM) was extracted from the wells and stored at −80°C before performing the cytokine assay. We performed a mouse pro‐inflammatory cytokine assay following the manufacturer's protocol (Neupane et al, 2021). This assay from Meso Scale Discovery (MSD) simultaneously tests for different mouse pro‐inflammatory cytokines including IFN‐γ, IL‐10, IL‐12p70, IL‐1β, and TNF‐α.…”

Targeting epigenetic modifiers to reprogramme macrophages in non-resolving inflammation-driven atherosclerosis

“…foam cell formation), which provides a rationale for developing the anti-inflammatory therapy by targeting the epigenetic modifiers that govern the phenotypic transition of macrophages, especially repolarization from pro-inflammatory (M1-like or inflammatory macrophages) to anti-inflammatory and pro-resolving (M2-like) phenotype as proposed in the alternative model for macrophage polarization. To this end, several macrophage-specific targeted approaches to polarize macrophages toward M2 have recently been investigated in AS or relevant inflammatory diseases, including pro-efferocytic nanoparticles, 128 injectable silk/sitagliptin gel scaffolds, 165 small molecule compounds, 166 macrophage-engineering vesicles, 167 SAA-containing HDL, 168 and CD137 agonists. 169 Of note, M1 may be less phenotypically plastic than M2, probably due to its greater epigenetic drift (e.g.…”

Targeting the innate immune system with nanoparticles for cancer immunotherapy

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