Protective effect of lipoic acid modification on brain dysfunctions of mice induced by mesoporous silica nanoparticles

•MSNs could cross the BBB and cause the brain dysfunction of mice.•MSNs could induce ROS generation and alternate JNK, p38 MAPK and caspase pathways.•The behavioral effects could be mediated via modification of lipoic acid on MSNs. Mesoporous silica nanoparticles (MSNs) have shown potential in biomedicine due to their structural advantages. However, little is known concerning their ability crossing blood-brain barrier (BBB), and potential adverse effects on the brain function associated with MSNs exposure and counterpart solution remains to be elucidated. The findings in the present study indicate that pristine MSNs destroy BBB and enter into the brain, and therefore, the brain functions such as social ability and cognition of the mice is impaired remarkably. The in vitro study indicates that the pristine MSNs inhibit cellular proliferation via generation of reactive oxygen species (ROS), which results in impaired mitochondrial function and activates cellular apoptosis via JNK and p38 MAPK (mitogen-activated protein kinase) signaling pathway. The in vivo study demonstrates that exposure to the MSNs triggers oxidative stress, activates mitochondrial apoptosis signaling pathways and the caspase family, and leads to cell apoptosis in the brain. The mitigated damages both in vitro and in vivo are observed after exposure to lipoic acid (LA) modified MSNs (MSN-LA). The integrated multilevel toxicity assessments also indicate that the brain dysfunction may be mitigated by the modification of LA, due to superior antioxidative property of LA.