The excessive depositions of β-amyloid (Aβ)
and abnormal
level of reactive oxygen species (ROS) are considered as the important
pathogenic factors of Alzheimer’s disease (AD). Strategies
targeting only one of them have no obvious effects in clinic. In this
study, a multifunctional nanocarrier CICe@M-K that crosses the blood–brain
barrier (BBB) efficiently was developed for inhibiting Aβ aggregation
and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer
IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their
surfaces were grafted with cerium oxide nanoparticles (CeO2 NPs) and a short peptide K (CKLVFFAED). Living imaging showed that
CICe@M-K was mainly distributed in the brain, liver, and kidneys,
indicating CICe@M-K crossed BBB efficiently and accumulated in brain.
After the irradiation of 808 nm laser, Cur was continuously released.
Both of Cur and the peptide K can recognize and bind to Aβ through
multiple interaction including π–π stacking interaction,
hydrophobic interaction, and hydrogen bond, inhibiting Aβ aggregation.
On the other hand, Cur and CeO2 NPs cooperate to relieve
the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aβ depositions,
alleviate oxidative stress, and improve cognitive ability of the APP/PS1
AD mouse model, which demonstrated that CICe@M-K is a potential agent
for AD treatment.