Background: To deliver drugs to treat Alzheimer’s Disease (AD), nanoparticles should
firstly penetrate through blood brain barrier, and then target neurons.
Methods: Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver
beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained,
the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo
neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good
stability when incubated with serum. In vivo, the treatment with ANNP/siRNA significantly improves
the spatial learning and memory of APP/PS1 double transgenic mice, as determined by mean escape
latency, times of crossing the platform area during the 60 s swimming and the percentage of the distance
in the target quadrant.
Results and Conclusion: After the treatment, BACE1 RNA level of ANNP/siRNA group was greatly
reduced, which contributed a good AD treatment outcome. Finally, after repeated administration, the
ANNP/siRNA did not lead to significant change as observed by HE staining of main organs, suggesting
the good biocompatibility of ANNP/siRNA. These results demonstrated that the ANNP was a good
candidate for AD targeting siRNA delivery.