Nucleus-Targeted Nanoparticles Induce Autophagy of Vascular Endothelial Cells in Cervical Spondylosis of Vertebral Artery Type Through PI3K/Akt/mTOR Signaling Pathway.

ABSTRACT

Nanoparticles are characterized by their large surface area per unit and high dispersion, with excellent affinity and adhesion to the tissue, which help them to contact drugs with tissues. However, the relationship between nuclear-targeted nanoparticles and PI3K/Akt/mTOR pathway, as well as their roles in cervical spondylosis of vertebral artery type (CSA) remain unclear. bEnd.3 cells were in this study exposed to nuclear-targeted nanoparticles, followed by determination of cell biological processes. The role of nuclear-targeted nanoparticles in CSA in relation to PI3K/Akt/mTOR pathway was then analyzed through detection of autophagy-related proteins pathway-related proteins. Nuclear-targeted nanoparticles led to reduced bEnd.3 cell proliferation with IC50 at indicated time points shown as (12.8±0.67), (8.8±0.43), and (4.6±0.42) µmol/L, respectively. Nuclear-targeted nanoparticles blocked bEnd.3 cells in G2/M phase, and induced apoptosis. In addition, nuclear-targeted nanoparticles inhibited the PI3K/Akt/mTOR pathway in the bEnd.3 cells, as evidenced by reduced PI3K, Akt and mTOR levels. Nuclear-targeted nanoparticles decreased the expression of Beclin-1, LC3, p62, Cathepsin D, and ATG5, and increased expression of GSK-3 and Bcl-2. Our present study demonstrated that the nucleartargeted nanoparticles could regulate the growth of bEnd.3 cells in CSA and promote autophagy of cells through blockage of the PI3K/Akt/mTOR signaling pathway.