Effect of intravenous poly(lactide-co-glycolide) nanoparticles on bleomycin pulmonary fibrosis

When delivered intravenously in vivo, NPs resolve established bleomycin-induced pulmonary fibrosis and invert the trajectory of over 1,000 genes from pre- to post-treatment according to bulk RNA-sequencing. NPs also suppress profibrotic signaling and increase expression of repair-associated pathways like peroxisome proliferator-activated receptor gamma (PPAR-γ), nuclear retinoic acid receptor (RAR), vascular endothelial growth factor (VEGF), and sphingolipid signaling in fibrotic lungs.

Flow cytometry confirms that NPs induce monocyte recruitment to fibrotic lungs via enhanced integrin expression. Altogether, NPs induce a robust pro-regenerative signature comprised of ECM degradation, inflammation resolution, and tissue repair pathways, concomitant with increased NP+ monocyte recruitment to fibrotic lungs. This work demonstrates that monocytes are not intrinsically profibrotic, but rather, their effects are context-dependent, and they retain a capacity for fibrotic resolution under conditions that can be induced by materials with translational potential.