Screening <i>Isodon rubescens</i>-Derived Vesicles Harvested at Different Periods as Carriers for the Treatment of Colitis-Associated Cancer

Plant-derived extracellular vesicles are of great significance in practical applications due to their availability, low immunogenicity, and effective carrier performance. <i>Isodon rubescens</i>-derived vesicles (IRDVs) not only have the capability for drug-carrying targeted therapy but also exhibit certain anti-inflammatory and antitumor effects as part of traditional Chinese medicine. The harvest time is closely related to the quality of its medicinal ingredients; however, whether there are differences in the IRDVs harvested at different times has yet to be explored. Herein, we analyzed the morphology and chemical composition of IRDVs collected at different time points and identified six-month-harvested IRDVs as the most suitable delivery vector. To further enhance their therapeutic potential, we modified the IRDVs with deoxycholic acid to facilitate the oral delivery of the chemotherapy drug doxorubicin (DOX). This novel nanotherapy, termed DOX-IRDVs@DA, was developed as an oral targeted treatment for colitis-associated cancer (CAC). The results demonstrated that DOX-IRDVs@DA effectively delivered DOX to colon tumor 26 (CT26) cells, induced cancer cell apoptosis by modulating apoptosis-related proteins, and inhibited the proliferation of CT26 cells. In vivo studies in a mouse model of CAC revealed that DOX-IRDVs@DA achieved superior targeted therapeutic effects, reducing the number of colonic nodules, restoring the structural integrity of the colon, and causing minimal systemic toxicity.