The Killing Effects Of Photosensitizer-loaded Hollow Silica Nanoparticles On Hepatoma Cell In Vitro And In Vivo

Background:This study examined the inhibitory effects of conventional photosensitizers and photosensitizers delivered in hollow silica nanoparticles on the proliferation of HepG2human hepatoma cells under different experimental conditions and the underlying mechanisms of these effects.Methods:Photosensitizers (conventional Photosan or nanoscale Photosan) were administered to in vivo and in vitro cultured HepG2hepatoma cells, and a semiconductor laser was used as a light source to photoirradiate these cells. Photodynamic therapies(PDTs) involving different levels of light exposure and different photosensitizer concentrations were tested; to assess the effects of these PDTs,the cellular viability was determined by3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry.The express of caspase-3and caspase-9caused in the photodynamic therapy by western blot. A nude mouse animal model was established to conduct in vivo experiments comparing the inhibitory effects of nanoscale photosensitizers and conventional photosensitizers on liver cancer.Results:Nanoscale photosensitizer-mediated PDTs produced significant inhibitory effects on liver cancer cells. Within a certain range of conditions, hepatoma cell viability significantly decreased as photosensitizer concentrations and laser doses increased. Moreover, under the same experimental conditions, the nanoscale photosensitizer performed better than the conventional photosensitizer.The flow cytometry demonstrated that the laser induced cell death with PS-loaded HSNP was much more severe than that of free PS. The activated forms the Caspase3and caspase-9expression with PS-loaded HSNP were significantly higher than free PS.In vivo experiments using either nanoscale photosensitizer or conventional photosensitizer in a nude mouse liver cancer model suggested that nanoscale photosensitizer treatments were superior to the corresponding conventional photosensitizer treatments in survival time and and nanoscale photosensitizer treatment group tumor volumewas significantly smaller than the size of conventional photosensitizer treatment groups.Conclusions:Hollow nanoparticles containing photosensitizer has stronger inhibited effect on hepatoma cells both in vivo and in vitro than conventional photosensitizer. These inhibitory effects may result from the induction of high levels of apoptosis-related protein expression, which trigger the activation of apoptotic pathways that cause the programmed death of cancer cells.