Investigation of the effect of hexagonal boron nitrides (hBNs) on mouse hippocampal cell line

It is a challenge to treat a neurological disease and brain cancer not only due to poor understanding of their molecular basis but also delivery of therapeutic drugs. In this thesis, it is aimed to understand the potential of hBNs as a therapetic agent to relieve cellular stress. First, the cytotoxicity of hBNs and their possible degradation product, boric acid (BA), on Embryonic Mouse Hippocampal Cell Line (mHippoE-14) was assessed in the concentration range of 10-1000 μg/mL for both materials for 24 h and 72 h exposure. It was found that both hBNs and BA showed concentration and time dependent cytotoxicity while hBNs were showing less cytotoxic behavior. Further; cell death mechanism, reactive oxygen species (ROS) generation, cell cycle, and apoptotic body formation were investigated using hBNs and BA concentrations with 4.4, 22, and 44 μg/mL boron content. hBNs drove the cells to apoptosis with the lowest concentration at 24 h exposure and with the increased exposure time the higher concentrations caused apoptosis as well. For BA, an increase in necrosis was observed at lowest two concentrations with 72 h of exposure. BA drove cells to apoptosis starting from the lowest concentration with both exposure times. Both hBNs and BA caused increased ROS production with the increased concentration and exposure times but the increase was more significant with BA exposure. 24 h exposure of hBNs and BA had no significant effect on cell cycle while 72 h exposure caused significant changes on cell cycle, especially on G0-G1 phase. Apoptotic bodies were not observed with any hBNs and BA concentrations and exposure times. The study was further expanded by exposing the cells to doxorubicin (DOX) to cause a stress on cells, and then were treated with hBNs and BA concentrations containing 4.4, 22 and 44 μg/mL boron and were exposed for 24 h and 72 h. It was found that both hBNs and BA increased cell viability when exposed for 72 h. This study suggests that hBNs and BA have very low toxicity and could be used as therapeutic agents at low concentrations to decrease oxidative stress caused by various drugs used for treatment of neurological diseases and brain cancer. However, since hBNs slowly degrade in biological medium, they can be used as a controlled releasing agent as compared to ionic BA in addition to their nanocarrier feature.