Macrophage Polarization as a Facile Strategy to Enhance Efficacy of Macrophage Membrane‐Coated Nanoparticles in Osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disorder associated with pain and inflammation, and is the leading cause of disability worldwide. Owing to the complexity of OA inflammation driven by a plethora of inflammatory cytokines, current specific anti‐cytokine therapies have not been successful. Among the immune cells implicated in OA inflammation, macrophages reportedly regulate OA inflammation via macrophage polarization. Given that pro‐inflammatory M1 and anti‐inflammatory M2 macrophages have opposing roles in OA inflammation, exploiting advanced polarization of macrophages to specific macrophage subsets (M0, M1, and M2) to enhance the therapeutic efficacy of macrophage membrane‐coated gold (Au) nanoparticles (NPs) as a broad‐spectrum anti‐inflammatory agent for OA treatment is proposed. Herein, it is shown that among the macrophage membrane‐coated NPs generated from the various macrophage subsets, M2 macrophage membrane‐coated nanoparticles (Au‐M2 NPs) uniquely exhibit superior efficacy in sponging the pro‐inflammatory cytokines and alleviating OA inflammation and matrix degradation over its counterparts derived from the same macrophage cell source, in both inflammation‐stimulated chondrocyte and explant OA models. Collectively, the herein described results validate macrophage polarization as a facile strategy to enhance the therapeutic efficacy of macrophage membrane NP‐based immunotherapy for potential OA treatment.

Bibliometric and visualization analysis of macrophages associated with osteoarthritis from 1991 to 2021

“…Since macrophage polarization plays a fundamental role in OA progression and regeneration, many efforts have been made to explore novel specific targets to inhibit or slow the progression of OA. For instance, M2 macrophage membrane-coated nanoparticles (Au-M2 NPs), a unique drug platform, could be applied as a highly anti-inflammatory and specific polarize macrophages to M2 type and eventually alleviate OA inflammation as well as matrix degradation ( 52 ). On the other hand, investigating the underlying molecular pathology of OA is also a pivotal research direction for differential treatment.…”

“…In addition, the mechanism research of macrophages has also drawn many researchers' attention. For example, NO was found to induce apoptosis and proinflammatory cytokines secretion, while others reported that it could protect chondrocytes and attenuates macrophagemediated inflammation (49)(50)(51)(52)(53). Therefore, exploring the mechanisms underlying on the macrophage and OA progression.…”

Macrophage cell membrane-based nanoparticles: a new promising biomimetic platform for targeted delivery and treatment

“…Alleviating OA inflammation and matrix degradation 3. Enhanced therapeutic efficiency [ 144 ] Allergic asthma BMMs PLGA Dnmt3aos In vitro: M2 macrophage In vivo: allergic asthma mice 1. Ameliorate allergic asthma with a marked reduction of lung inflammation 2.…”

Recent Advances in Nano-Therapeutic Strategies for Osteoarthritis

“…The researchers revealed a promising therapeutic strategy to break a vicious and self-perpetuating cycle in OA patients. Teo et al purposed a facile strategy to improve the efficacy of the macrophage membrane-derived nanoparticles ( Teo et al, 2022 ). They prepared pro-inflammatory M1 and anti-inflammatory M2 macrophages through cell polarization, and then constructed M2 macrophage membrane-coated gold nanoparticles (Au-M2 NPs).…”