Recent updates on engineered nanomedicines for treatment of fibrosis.

Fibrotic disorders represent a worldwide health concern, leading to progressive dysfunction across multiple organs such as lung, liver, kidney, and heart. Fibrosis occurs due to persistent inflammation, coupled with differentiation of fibroblasts into matrix-producing myofibroblasts and progressive deposition of extracellular matrix (ECM) components. Although nintedanib and pirfenidone are clinically approved as antifibrotic drugs, they offer only limited therapeutic benefit because of their inadequate tissue selectivity, poor bioavailability, and systemic toxicity. In recent years, engineered nanomedicines emerged as promising strategies to improve drug bioavailability, enable fibrotic matrix penetration, and allow selective targeting of activated fibroblasts. Diverse types of nanocarriers including lipid-based nanoparticles (NPs), polymeric nanocarriers, and inorganic NPs, have shown promising antifibrotic efficacy across multiple organs by increasing drug accumulation in fibrotic tissue and remodeling the phenotype of fibroblasts thereby halting ECM production. Some nanomedicine strategies were also designed to simultaneously address both inflammation and fibrosis by targeting multiple cell types such as epithelial cells, macrophages, or fibroblasts. In addition, theranostic nanocarriers were developed for detection and treatment of fibrosis. This review highlights the recent progress in nanomedicine strategies for treatment of fibrotic disorders and discusses mechanistic aspects of fibrosis remodeling using nanomedicines.