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 H₂O₂, 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 H₂O₂-induced NAD(+) and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H₂O₂-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 H₂O₂-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.