Synthesis of folic acid-tailored chitosan-coated exosomes for targeted delivery of 5-fluorouracil to triple-negative breast cancer cells.

The use of anticancer drugs is integral to cancer treatment programs. However, the drawbacks of these chemotherapeutic agents, coupled with the problem of drug resistance, remain significant challenges. To address this, we developed a drug delivery platform based on exosomes derived from HEK293 cells, combined with folic acid-conjugated chitosan (FA-CS). The formulation, FA-CS-PEG-5FU@HEK-EXs, exhibited a polydispersity index (PDI) of 0.140, a zeta size of 188.30 nm, and a zeta potential of 3.60 mV. Its cytotoxicity to healthy tissue was negligible; however, at a dose of 500 μg/mL, the survival rate of breast cancer MDA-MB-231 cells decreased to approximately 50 %. Fluorescence staining indicated that FA-CS-PEG-5FU@HEK-EXs induced cell death in cancer cells by increasing reactive oxygen species levels, compromising the mitochondrial membrane potential, and nucleus. Furthermore, FA-CS demonstrated synergistic effects with 5FU, inducing the necrotic cell death (44.6 %). In conclusion, this study demonstrates that using exosomes to deliver the anticancer drug 5FU enhances the drug's therapeutic efficacy. Moreover, compared to conventional cancer therapies, FA-CS-PEG-5FU@HEK-EXs can minimize systemic side effects in clinical applications while enhancing drug utilization, stability, and cellular uptake, leading to highly effective treatment outcomes. The safe and efficient exosome-based platform with significant potential to inhibit tumor proliferation, offering promising insights for future clinical cancer therapies.