Preparation of oridonin-loaded microalgae-derived small extracellular vesicles and their anti-colorectal cancer efficacy evaluation

Some Chinese medicine monomers are limited in clinical application due to poor targeting and in vivo stability, strong hydrophobicity, low bioavailability, short half-life, and systemic toxicity within the therapeutic dose range, etc. Combining these monomers with nanotechnology-based drug delivery systems can further improve the targeting and clinical efficacy of these drugs. Thus, this study, constructed a drug delivery vector targeting colorectal cancer (CRC), i.e. cRGD-Ds-sEVs with cRGD-modified small extracellular vesicles of Dunaliella salina (Ds-sEVs), and their effects of targeting and anti-CRC were investigated at the cellular level in vitro and in animal model in vivo. The results verified that the anti-CRC effect is cRGD-Ds-sEVs/ORI > Ds-sEVs/ORI > ORI in vitro. In vivo studies showed that anti-tumor effect of CRC in nude mice was cRGD-Ds-sEVs/ORI > ORI. In addition, compared with non-cRGD-modified Ds-sEVs, cRGD-modified Ds-sEVs showed stronger targeting to HCT-116 cells. Furthermore, cRGD-Ds-sEVs/ORI showed significantly higher accumulation in nude mouse tumor tissues than non-cRGD-modified Ds-sEVs/ORI and free ORI, directly enhancing its in vivo anti-tumor activity by concentrating ORI at tumor sites. Summarily, our study proved that we have successfully constructed a drug delivery system (i.e. cRGD-Ds-sEVs/ORI) that targets CRC, and it exhabits a better anti-CRC activity both in vivo and in vitro. It provided a promising targeted delivery strategy for hydrophobic Chinese medicine monomers like ORI, laying a solid experimental foundation for their potential clinical translation and offering new insights into the application of nanotechnology in optimizing the therapeutic efficacy of traditional Chinese medicine against malignant tumors.