ABSTRACT
Recently, various attempts have been made to apply diverse types of nanoparticles in biotechnology. Silica nanoparticles (SNPs) have been highlighted and studied for their selective accumulation in diseased parts, strong physical and chemical stability, and low cytotoxicity. SNPs, in particular, are very suitable for use in drug delivery and bioimaging, and have been sought as a treatment for ischemic diseases. In addition, mesoporous silica nanoparticles have been confirmed to efficiently deliver various types of drugs owing to their porous structure. Moreover, there have been innovative attempts to treat ischemic diseases using SNPs, which utilize the effects of Si ions on cells to improve cell viability, migration enhancement, and phenotype modulation. Recently, external stimulus-responsive treatments that control the movement of magnetic SNPs using external magnetic fields have been studied. This review addresses several original attempts to treat ischemic diseases using SNPs, including particle synthesis methods, and presents perspectives on future research directions.
ABSTRACT
BACKGROUND@#Various cell-culture systems have been used to evaluate drug toxicity in vitro. However, factors that affect cytotoxicity outcomes in drug toxicity evaluation systems remain elusive. In this study, we used multilayered sheets of cardiac-mimetic cells, which were reprogrammed from human fibroblasts, to investigate the effects of the layer number on drug cytotoxicity outcomes. @*METHODS@#Cell sheets of cardiac-mimetic cells were fabricated by reprogramming of human fibroblasts into cardiacmimetic cells via coculture with cardiac cells and electric stimulation, as previously described. Double-layered cell sheets were prepared by stacking the cell sheets. The mono- and double-layered cell sheets were treated with 5-fluorouracil (5-FU), an anticancer drug, in vitro. Subsequently, apoptosis and lipid peroxidation were analyzed. Furthermore, effects of cardiacmimetic cell density on cytotoxicity outcomes were evaluated by culturing cells in monolayer at various cell densities. @*RESULTS@#The double-layered cell sheets exhibited lower cytotoxicity in terms of apoptosis and lipid peroxidation than the mono-layered sheets at the same 5-FU dose. In addition, the double-layered cell sheets showed better preservation of mitochondrial function and plasma membrane integrity than the monolayer sheets. The lower cytotoxicity outcomes in the double-layered cell sheets may be due to the higher intercellular interactions, as the cytotoxicity of 5-FU decreased with cell density in monolayer cultures of cardiac-mimetic cells. @*CONCLUSION@#The layer number of cardiac-mimetic cell sheets affects drug cytotoxicity outcomes in drug toxicity tests.The in vitro. cellular configuration that more closely mimics the in vivo configuration in the evaluation systems seems to exhibit lower cytotoxicity in response to drug.
ABSTRACT
BACKGROUND@#Various cell-culture systems have been used to evaluate drug toxicity in vitro. However, factors that affect cytotoxicity outcomes in drug toxicity evaluation systems remain elusive. In this study, we used multilayered sheets of cardiac-mimetic cells, which were reprogrammed from human fibroblasts, to investigate the effects of the layer number on drug cytotoxicity outcomes. @*METHODS@#Cell sheets of cardiac-mimetic cells were fabricated by reprogramming of human fibroblasts into cardiacmimetic cells via coculture with cardiac cells and electric stimulation, as previously described. Double-layered cell sheets were prepared by stacking the cell sheets. The mono- and double-layered cell sheets were treated with 5-fluorouracil (5-FU), an anticancer drug, in vitro. Subsequently, apoptosis and lipid peroxidation were analyzed. Furthermore, effects of cardiacmimetic cell density on cytotoxicity outcomes were evaluated by culturing cells in monolayer at various cell densities. @*RESULTS@#The double-layered cell sheets exhibited lower cytotoxicity in terms of apoptosis and lipid peroxidation than the mono-layered sheets at the same 5-FU dose. In addition, the double-layered cell sheets showed better preservation of mitochondrial function and plasma membrane integrity than the monolayer sheets. The lower cytotoxicity outcomes in the double-layered cell sheets may be due to the higher intercellular interactions, as the cytotoxicity of 5-FU decreased with cell density in monolayer cultures of cardiac-mimetic cells. @*CONCLUSION@#The layer number of cardiac-mimetic cell sheets affects drug cytotoxicity outcomes in drug toxicity tests.The in vitro. cellular configuration that more closely mimics the in vivo configuration in the evaluation systems seems to exhibit lower cytotoxicity in response to drug.