Targeted drug delivery to colon cancer cells can significantly enhance the therapeutic efficiency. Herein, we developed 5-fluorouracil (5-FU)-loaded amino-functionalized mesoporous silica nanoparticle (MSN-NH2)-based galactosylated chitosans (GCs), which are galactose receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, nitrogen sorption and dynamic light scattering. Drug loading capacity and drug release properties were determined by ultraviolet spectrophotometry. 5-FU@MSN-NH2/GC showed high loading capacity and possessed much higher cytotoxicity on human colon cancer cells (SW620 cells) than 5-FU@MSN-NH2 and free 5-FU. But, MSN-NH2/GC did not show significant cytotoxicity. Subsequently, 5-FU@MSN-NH2/GC anti-cancer activity on SW620 cells in vitro was confirmed by cell apoptosis. These results are consistent with the cellular uptake test in which MSN-NH2/GC could specifically recognize and bind to cancer cells by the galectin-receptor recognition. But, it is found that pre-addition of galactose in the medium, leading to competitive binding to the galectin receptor of SW620 cells, resulted in a decrease in the binding of MSN-NH2/GC to the galectin receptor. The results demonstrated the inorganic-organic nanocomposite could be used as a promising drug delivery carrier for the targeted delivery of drug into galectin-positive colon cancer cells to improve therapeutic index while reducing side effects.
Keywords: 5-fluorouracil; colon cancer; galactosylated chitosan; mesoporous silica.