Indeed, the use of conventional Photosan at higher concentrations and longer incubation still produced cell death rates significantly lower than that observed in the nanoscale Photosan groups. In addition, we demonstrated that apoptosis is involved in cell death triggered by conventional Photosan and nanoscale Photosan. Interestingly, nanoscale Photosan-mediated PDT produced a higher proportion of apoptotic cells than conventional Photosan. Furthermore, in in vivo experiments using a mouse model liver cancer, changes in tumor volume, tumor growth, and mean mouse survival times in response
to treatment were assessed, after treatment with the two photosensitizer types. Our results clearly SGLT inhibitor indicated that significantly better therapeutic efficacy was obtained with nanoscale photosensitizers. These data were in agreement with the in vitro findings and provide a solid basis for future clinical trials of photosensitizer carriers. The mechanisms underlying PDT-induced apoptosis mainly involved two signaling pathways: (1) death receptor-mediated exogenous pathway
and (2) mitochondria-mediated endogenous pathway. It is known that activation of the endogenous pathway rather than the exogenous pathway is typically the main cause of PDT-induced apoptosis [24–26]. Cytoplasmic cytochrome C (Cyc) and apoptotic protease-activating factor 1 (Apaf-1) form a heptameric apoptotic complex that binds to, cleaves, and thereby activates the AZD3965 caspase-9 zymogen. Caspase-9 hydrolyzes and activates caspase-3/7, which reaches the same termination point produced by the aforementioned exogenous pathway [27–29]. GSK2126458 purchase The death receptor-mediated exogenous (caspase-8) pathway
ultimately activates caspase-3 to induce apoptosis. Thus, both pathways eventually induce apoptosis through caspase activation. Our experiments showed that PDT cells exhibited significantly enhanced levels of active caspase-3 and caspase-9 proteins, which were significantly higher in nanoscale Photosan group compared with conventional Photosan group. These findings indicated that both Photosan-mediated PDT induce tumor cell apoptosis via endogenous and exogenous pathways. Relative to conventional photosensitizers, nanoscale photosensitizers exhibited enhanced photochemical efficacy and higher water solubility, and increased effective drug concentrations in tumor tissues. Thanks to these properties, the use of nanoscale enhances the effects Phosphoprotein phosphatase of photosensitizer PDT of tumor cells. Conclusion In summary, we performed the in vivo and in vitro evaluation of the cytotoxic effects of Photosan-loaded hollow silica nanoparticles on liver cancer cells. The results showed that nanoscale photosensitizers were more effective in inhibiting liver cancer cells compared with conventional photosensitizer, both in vitro and in vivo. Acknowledgements This work was supported by the National Natural Science Foundation of China (Grant No.81372628, 51021063), the Planned Science and Technology Project of Hunan province (Grant No.