NAD+-Carrying Mesoporous Silica Nanoparticles Can Prevent Oxidative Stress-Induced Energy Failures of Both Rodent Astrocytes and PC12 Cells

Aim To test the hypothesis that NAD + -carrying mesoporous silica nanoparticles (M-MSNs@NAD+) can effectively deliver NAD + into cells to produce cytoprotective effects. Methods & Materials NAD + was incorporated into M-MSNs. Primary rat astrocyte cultures and PC12 cells were treated with H 2 O 2 , followed by post-treatment with M-MSNs@NAD+. After various durations of the post-treatment, intracellular NAD + levels, intracellular ATP levels and lactate dehydrogenase (LDH) release were determined. Results & Discussion M-MSNs can be effectively loaded with NAD + . The M-MSNs@NAD+ can significantly attenuate H 2 O 2 -induced NAD + and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H 2 O 2 -induced LDH release from both astrocyte cultures and PC12 cells. In contrast, the NAD + that is spontaneously released from the M-MSNs@NAD+ is insufficient to prevent the H 2 O 2 -induced damage. Conclusions Our study has suggested the first approach that can effectively deliver NAD + into cells, which provides an important basis both for elucidating the roles of intracellular NAD + in biological functions and for therapeutic applications of NAD + . Our study has also provided the first direct evidence demonstrating a key role of NAD + depletion in oxidative stress-induced ATP decreases.