Development of cell derived nanovesicle from pancreatic stellate cells as a novel drug delivery system

Abstract

Pancreatic ductal adenocarcinoma is one of the major subtypes of pancreatic cancer and is a common type, accounting for approximately 90% of pancreatic cancer patients. The 5-year survival rate for pancreatic ductal adenocarcinoma is very low, approximately 5%. One of the main problems with this type of cancer is a phenomenon known as desmoplasia. This means that the extracellular matrix (ECM) and fibroblasts form abnormal tissue around the tumor site. This phenomenon causes many treatment difficulties and drug resistance in pancreatic ductal adenocarcinoma. Cancer cells are surrounded by extracellular matrix and fibroblasts, so anticancer drugs cannot be delivered to the cancer cells, resulting in drug resistance. To overcome these problems, efforts are being made to develop new drug delivery systems utilizing cell-derived nanovesicles. This system utilizes cell-derived nanovesicles derived from pancreatic stellate cells, the main constituent cells of desmoplasia, and utilizes the blast cell homing reaction, which is one of the characteristics of exosomes. And this regression reaction has similar characteristics to cell-derived nanovesicles, which are artificial exosomes. We created a nanovesicle made by encapsulating a drug in a cell-derived nanovesicle and confirmed its drug delivery ability through experiments, but additional research on the drug encapsulation efficiency is needed. If these limitations are overcome, drug encapsulated cell-derived nanovesicles can be used in patients with pancreatic ductal adenocarcinoma to increase drug targeting efficiency, reduce concerns about drug side effects with less drug usage than before, and better treatment effects can be expected. In addition, cell- derived nanovesicles, similar to exosomes, have low immunogenicity, high targeting efficiency, and drug delivery ability, so it is expected that they will present new possibilities for the treatment of pancreatic ductal adenocarcinoma through the development of new drug carriers. Keywords: Exosome, Pancreatic ductal adenocarcinoma, Desmoplasia, Cell derived nanovesicle, drug delivery