Mesoporous Polydopamine Loaded Pirfenidone Target to Fibroblast Activation Protein for Pulmonary Fibrosis Therapy

Abstract

Recently, fibroblast activation protein (FAP), an overexpressed transmembrane protein of activated fibroblast in pulmonary fibrosis, has been considered as the new target for diagnosing and treating pulmonary fibrosis. In this work, mesoporous polydopamine (MPDA), which is facile prepared and easily modified, is developed as a carrier to load antifibrosis drug pirfenidone (PFD) and linking FAP inhibitor (FAPI) to realize lesion-targeted drug delivery for pulmonary fibrosis therapy. We have found that PFD@MPDA-FAPI is well biocompatible and with good properties of antifibrosis, when ICG labels MPDA-FAPI, the accumulation of the nanodrug at the fibrosis lung in vivo can be observed by NIR imaging, and the antifibrosis properties of PFD@MPDA-FAPI in vivo were also better than those of pure PFD and PFD@MPDA; therefore, the easily produced and biocompatible nanodrug PFD@MPDA-FAPI developed in this study is promising for further clinical translations in pulmonary fibrosis antifibrosis therapy.

The research progress of anti-inflammatory and anti-fibrosis treatment of chronic pancreatitis

“…Pirfenidone is a pyridine ketone compound with a broad-spectrum anti-fibrotic effect that has shown good results in the treatment of idiopathic pulmonary fibrosis, liver fibrosis, and other fibrotic diseases ( 106 , 107 ).…”

FAP Targeting of Photosensitizer-Loaded Polymersomes for Increased Light-Activated Cell Killing

“…Besides cancer-associated fibroblasts (CAFs), many cancer types express FAP at different levels, and across most cancer types, elevated FAP is associated with worse clinical outcomes. − Therefore, targeting FAP represents a key aspect in improving the uptake of PSs. While it has been reported that inhibitors of FAP can improve nanoparticle targeting to CAFs, their potential to increase the efficacy of PS-loaded nanocarriers and thus offer efficient PDT solutions has not yet been explored.…”

“… 27 − 29 Therefore, targeting FAP represents a key aspect in improving the uptake of PSs. While it has been reported that inhibitors of FAP can improve nanoparticle targeting to CAFs, 30 their potential to increase the efficacy of PS-loaded nanocarriers and thus offer efficient PDT solutions has not yet been explored.…”

Fibroblast Activating Protein: Skimming the Surface of Molecular Imaging to Assess Fibrotic Disease Activity

“…However, increased expression may not be detrimental; a recent study showed that depletion of FAP + cells or genetic deletion of FAP exacerbated fibrosis in a murine model of repetitive bleomycin injury and had no impact on fibrosis induced by adenoviral overexpression of TGF-β ( 7 ). Regardless of its role in pathogenesis, recent studies have used FAP to direct delivery of approved and emerging antifibrotic drugs, supporting its potential as an indicator of active wound repair and fibrosis ( 8 , 9 ).…”