Cancer-Associated Fibroblast-Targeted Delivery of Captopril to Overcome Penetration Obstacles for Enhanced Pancreatic Cancer Therapy

Pancreatic cancer is one of the most stroma-abundant solid cancers. Its desmoplastic nature restricts the penetration of drugs in tumor tissues and is considered as a major challenge for efficient chemotherapy. In the present study, we repurposed the use of captopril to deplete the overexpressed extracellular matrix (ECM) in stroma of pancreatic tumor. Precise delivery of captopril to cancer-associated fibroblasts (CAFs) was achieved using CAFs targeting peptide modified liposomes. The targeted delivery of captopril significantly downregulated the deposition of ECM by blocking the TGF-β1-Smad2 related signaling pathway, which improved the penetration of subsequently administrated liposome-encapsulated chemotherapeutic agent gemcitabine. It proved as a promising solution to break the aforementioned stromal barrier in pancreatic cancer therapy.