PLG nanoparticles target fibroblasts and MARCO+ monocytes to reverse multiorgan fibrosis

• DOI: 10.1172/jci.insight.151037
• Publication Date: 2022-02-01T17:04:09Z
• Authors: Dan Xu; Swati Bhattacharyya; Wenxia Wang; Igal Ifergan; Ming-Yi Alice Chi...; Daniele Procissi; Anjana Yeldandi; Swarna Bale; Roberta Goncalves...; Craig Horbinski; Stephen D. Miller; John Varga
• Keywords: Myofibroblast

Systemic sclerosis (SSc) is a chronic, multisystem orphan disease with highly variable clinical course, high mortality rate, and poorly understood complex pathogenesis. We have identified an important role for subpopulation of monocytes macrophages characterized by surface expression the scavenger receptor macrophage collagenous structure (MARCO) in chronic inflammation fibrosis SSc preclinical models. show that MARCO+ accumulate lesional skin lung topographic proximity to activated myofibroblasts patients bleomycin-induced mouse model SSc. Short-term treatment mice potentially novel nanoparticle, poly(lactic-co-glycolic) acid (PLG), which composed carboxylated, FDA-approved, biodegradable polymer modulates activation trafficking inflammatory monocytes, markedly attenuated fibrosis. Mechanistically, isolated cells culture, PLG nanoparticles inhibited TGF-dependent fibrotic responses vitro. Thus, are potent effector can be therapeutically targeted using nanoparticles.