Pirfenidone-loaded exosomes derived from pancreatic ductal adenocarcinoma cells alleviate fibrosis of premetastatic niches to inhibit liver metastasis.

Abstract

Given the metastasis-promoting effect of pancreatic ductal adenocarcinoma (PDAC)-derived exosomes through activation of fibrotic premetastatic niches, targeting and intervening in premetastatic organs to inhibit distant metastasis have challenged researchers and clinicians. Herein, a self-biomimetic drug delivery system based on exosomes derived from PDAC (PF@PCCEs) was constructed to precisely deliver an antifibrotic drug (pirfenidone, PF) to fibrotic premetastatic organs. First, PDAC-derived exosomes were confirmed to remarkably promote liver fibrosis. Then the prepared PF@PCCEs were actively internalized by HSCs (hepatic stellate cells) and subsequently alleviated the activation of HSCs. Delivery of PF to the premetastatic liver affected the niche suitable for the colonization of circulating tumour cells, further suppressing liver metastasis of PDAC. Thus, the strategy for intervening in the formation of fibrotic premetastatic niches to inhibit liver metastasis of PDAC using PF@PCCEs might offer inspiration for the treatment of tumour metastasis.

• Authors: Jing Zhao, Yun Zhu, Zhuojin Li, Jiawei Liang, Yin Zhang, Siqi Zhou, Yixuan Zhang, Zhiwen Fan, Yonghua Shen, Yifeng Liu, Feng Zhang, Shanshan Shen, Guifang Xu, Lei Wang, Ying Lv, Shu Zhang, Xiaoping Zou
• Journal: Biomaterials science (Biomater Sci) Vol. 10 Issue 22 Pg. 6614-6626 (Nov 08 2022) ISSN: 2047-4849 [Electronic] England
• PMID: 36260512 (Publication Type: Journal Article)

Chemical References

• pirfenidone

Topics

• Humans
• Exosomes
• Cell Line, Tumor
• Carcinoma, Pancreatic Ductal (drug therapy, pathology)
• Pancreatic Neoplasms (drug therapy, pathology)
• Liver Neoplasms (pathology)
• Liver Cirrhosis (drug therapy, pathology)
• Pancreatic Neoplasms