Construction of dunaliella salina-derived exosome-like nanovesicles co-delivery system for ICG and 5-FU and its enhanced suppression in triple-negative breast cancer cell

A common strategy in cancer therapy involves using a nanoscale carrier to simultaneously deliver phototherapeutic agents and chemotherapeutic drugs. However, traditional delivery carriers are toxic and immunogenic, and their preparation involves complex procedures, limiting their widespread application. Exosomes, are spherical, lipid bilayer vesicles ranging from 50 to 150 nm in diameter, which are naturally secreted by various cells, and can cross various biological barriers, making them attractive alternatives. Dunaliella salina-derived exosome-like nanovesicles (DENVs) represent promising drug nanocarriers owing to their favorable bio-compatibility, low immunogenicity, cost-effective, large-scale, and rapid production. However, the role of DENV in triple-negative breast cancer (BC) remains unknown. In this study, DENV were prepared by ultracentrifugation. Indocyanine green (ICG) and 5-fluorouracil (5-FU) were co-loaded into DENV (DENV-ICG/5-FU) via electroporation. DENV-ICG/5-FU exhibited good photothermal performance and stability. At a pH of 5.0 and exposure to 808 nm near-infrared (NIR) light (1 W cm^-2, 5 min), the cumulative release of 86.45% for 5-FU from the DENV-ICG/5-FU was observed. In addition, DENV-ICG/5-FU was internalized into 4T1 cells. Under NIR irradiation, it inhibited proliferation and migration and induced apoptosis of 4T1 cells. Results from flow cytometry and DCFH-DA analyses indicated that NIR irradiation markedly elevated both the percentage of cells in the G1 phase and the generation of reactive oxygen species. Mechanistic studies showed that under NIR irradiation, DENV-ICG/5-FU enhanced the expression of the pro-apoptotic protein Bax. In conclusion, these findings suggest that DENV could be ideal vehicles to co-deliver phototherapeutic agents and chemotherapeutic drugs for synergistic tumor treatment.