Biomimetic Nanoparticles Carrying EP300 Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible lung disease with limited treatment options. SGC-CBP30, a CBP/EP300 inhibitor, shows anti-fibrotic activity but suffers from poor bioavailability and tissue specificity. Here, we developed platelet membrane-coated nanoparticles (PNP) for targeted pulmonary delivery of SGC-CBP30 to enhance therapeutic efficacy. PNP was generated by encapsulating SGC-CBP30 in Poly (lactic-co-glycolic acid) (PLGA) nanoparticles coated with platelet membranes. Efficacy, biodistribution, and safety were evaluated in TGF-β1-stimulated PA317 cells and a BLM-induced pulmonary fibrosis model using immunofluorescence, Western blot, histology, PFTs (Pulmonary Function Tests), imaging, and serum biochemistry. PNP suppressed fibrotic markers (COL6A1, α-SMA, FN1, COL1A1) in vitro and showed lung-targeted delivery in vivo, improving lung function and reducing inflammation and fibrosis in BLM mice without detectable toxicity. Lung-targeted CBP/EP300 inhibition by PNP represents a biomimetic, translatable approach for anti-fibrotic therapy with potential extrapolation to other fibrotic diseases.