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.