Innovative Strategy for Enhanced Delivery of Anti-Fibrotic miR-150 via PDGFR-Targeted Exosomes for Fibrosis Treatment.

BACKGROUND

Fibrosis, caused by hepatic stellate cell (HSC) activation and resulting in extracellular matrix accumulation, cirrhosis, and ultimately liver failure, remains a critical challenge. Recent advances in exosome-based drug delivery systems offer an innovative approach by specifically targeting activated HSCs to combat fibrotic diseases. This study evaluated the anti-fibrotic potential of miR-150-loaded exosomes engineered with platelet-derived growth factor receptor (PDGFR)-targeting peptides for precise delivery to activated HSCs.

METHODS

Adipose-derived stem cells were genetically engineered to express PDGFR-targeting peptides via pDisplay vectors, resulting in the production of targeted exosomes (tEx). Subsequently, miR-150 was loaded into the targeted exosomes, termed tEx. In vitro and in vivo studies were conducted using a thioacetamide-induced liver fibrosis model.

RESULTS

Either real-time polymerase chain reaction or western blot analysis demonstrated that tEx significantly reduced fibrotic markers, including alpha-smooth muscle actin, collagen type I alpha 1 chain, and transforming growth factor beta 1, both in vitro and in vivo. Western blotting showed a 40% decrease in collagen deposition, while enzyme-linked immunosorbent assay indicated a 30% reduction in serum liver enzyme levels (aspartate transaminase and alanine aminotransferase) compared to controls. Immunohistochemical analysis demonstrated that tEx significantly reduced fibrosis markers and collagen deposition in liver tissues compared to controls, highlighting their strong anti-fibrotic and anti-inflammatory potential (P < 0.05).

CONCLUSION

The findings highlight the potential of PDGFR-tEx for efficient miR-150 delivery, demonstrating improved therapeutic efficacy with reduced systemic toxicity. This targeted approach may offer a more precise and effective treatment for liver fibrosis, surpassing conventional methods.