Synthesis of Biotin-Modified Galactosylated Chitosan Nanoparticles and Their Characteristics in Vitro and in Vivo.

BACKGROUND/AIMS: Our previous study found that a nanoparticle drug delivery system that operates as a drug carrier and controlled release system not only improves the efficacy of the drugs but also reduces their side effects. However, this system could not efficiently target hepatoma cells. The aim of this study was to synthesize biotin-modified galactosylated chitosan nanoparticles (Bio-GC) and evaluate their characteristics in vitro and in vivo.

METHODS

Bio-GC nanomaterials were synthesized, and confirmed by fourier transform infrared spectroscopy (FT-IR) and hydrogen-1 nuclear magnetic resonance (1H-NMR). The liver position and cancer target property of Bio-GC nanoparticles in vitro and in vivo was tested by confocal laser and small animal imaging system. The characteristics of Bio-GC/5-fluorouracil (5-FU) nanoparticles in vitro and in vivo were explored by cell proliferation, migration and cytotoxicity test, or by animal experiment.

RESULTS

Bio-GC nanoparticles were synthesized with biodegradable chitosan as the nanomaterial skeleton with biotin and galactose grafts. Bio-GC was confirmed by FT-IR and 1H-NMR. Bio-GC/5-FU nanoparticles were synthesized according to the optimal mass ratio for Bio-GC/5-FU (1: 4) and had a mean particle size of 81.1 nm, zeta potential of +39.2 mV, and drug loading capacity of 8.98%. Bio-GC/5-FU nanoparticles had sustained release properties (rapid, steady, and slow release phases). Bio-GC nanoparticles targeted liver and liver cancer cell in vitro and in vivo, and this was confirmed by confocal laser scanning and small animal imaging system. Compared with GC/5-FU nanoparticles, Bio-GC/5-FU nanoparticles showed more specific cytotoxic activity in a dose- and time-dependent manner and a more obvious inhibitory effect on the migration of liver cancer cells. In addition, Bio-GC/5-FU nanoparticles significantly prolonged the survival time of mice in orthotopic liver cancer transplantation model compared with other 5-FU nanoparticles or 5-FU alone. Bio-GC (0.64%) nanomaterial had no obvious cytotoxic effects on cells; thus, the concentration of Bio-GC/5-FU nanoparticles used was only 0.04% and showed no toxic effects on the cells.

CONCLUSION

Bio-GC is a liver- and cancer-targeting nanomaterial. Bio-GC/5-FU nanoparticles as drug carriers have stronger inhibitory effects on the proliferation and migration of liver cancer cells compared with 5-FU in vitro and in vivo.