Inhibitory of active dual cancer targeting 5-Fluorouracil nanoparticles on liver cancer in vitro and in vivo

Abstract In the previous experiments, biotin (Bio) was grafted onto CS to synthesize biotin-modified chitosan (Bio-CS) with liver cancer targeting efficacy, but there is still room for improvement in the targeting of Bio-CS to liver cancer. Based on the high expression of folate (FA) receptors on the surface of liver cancers, FA was grafted onto Bio-CS by chemical synthesis to optimize the synthesis of folic acid-modified biotinylated chitosan (FA-CS-Bio), verified by infrared spectroscopy and 1H-NMR. FA-CS-Bio/Fluorouracil (5-FU) nanoparticles had an obvious sustained release effect. Compared with Bio-CS, FA-CS-Bio could promote the inhibition of the proliferation and migration of liver cancer by 5-FU, and the concentration of 5-FU in hepatoma cells was significantly increased. Laser confocal experiments confirmed that FA-CS-Bio caused a significant increase in the fluorescence intensity in liver cancer cells. In terms of animal experiments, FA-CS-Bio increased the concentration of 5-FU in liver cancer tissue by 1.6 times on the basis of Bio-CS and the number of monophotons in liver cancer tissue by in vivo dynamic imaging experiments was significantly stronger than that of Bio-CS, indicating that the targeting ability of FA-CS-Bio was further improved. Compared with Bio-CS, FA-CS-Bio can significantly prolong the survival time of an orthotopic liver cancer transplantation model in mice and has a relieving effect on liver function damage and bone marrow suppression caused by 5-FU. In conclusion, FA-CS-Bio has significantly improved liver cancer targeting ability, prolonged the survival period of tumor-bearing mice, and alleviated the toxic and side effects caused by 5-FU.