Nitric oxide release in human aortic endothelial cells mediated by delivery of amphiphilic polysiloxane nanoparticles to caveolae.
Microdomains such as lipid raft and caveolae are organized as functional compartments in plasma membrane of cells. In this study, we note the functional platform of caveolae with dual functions, internalization of external substances and cell signalings leading to nitric oxide release, and hypothesize that the switching of enzyme activity of endothelial nitric oxide synthase can be achieved by targeting caveolae with nanoparticles. We prepared polysiloxane nanoparticles and studied cellular uptake of the nanoparticles and its concomitant influence on the nitric oxide release in human aortic endothelial cells. We found that polysiloxane nanoparticles were endocytosed via caveolae in human aortic endothelial cells and that enhanced nitric oxide release was followed by the cellular uptake of the nanoparticles. Furthermore, we confirmed that endothelial nitric oxide synthase was activated during cellular uptake of the nanoparticles. These findings support our idea that delivery of the polymeric nanoparticles to endothelial cells can lead to the induction of nitric oxide release.
Nishikawa
Takehiro
T
National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan. tnishi@ri.ncvc.go.jp
Iwakiri
Norio
N
Kaneko
Yoshiro
Y
Taguchi
Akihiko
A
Fukushima
Kazuhito
K
Mori
Hidezo
H
Morone
Nobuhiro
N
Kadokawa
Jun-ichi
J
D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D021941:Caveolae / Q000378:metabolism*; D002478:Cells, Cultured; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053758:Nanoparticles; D009569:Nitric Oxide / Q000378:metabolism*; D012833:Siloxanes / Q000737:chemistry*
D012833:Siloxanes; D009569:Nitric Oxide