TY - JOUR
T1 - An apolipoprotein e modified liposomal nanoparticle
T2 - Ligand dependent efficiency as a siRNA delivery carrier for mouse-derived brain endothelial cells
AU - Tamaru, Mina
AU - Akita, Hidetaka
AU - Kajimoto, Kazuaki
AU - Sato, Yusuke
AU - Hatakeyama, Hiroto
AU - Harashima, Hideyoshi
N1 - Funding Information:
This work was supported in part by Funding Program for Next Generation World-Leading Researchers (NEXT Program) , and partially by a Grant for Industrial Technology Research from New Energy and Industrial Technology Development Organization (NEDO) . H.A. is also supported by the Uehara Memorial Foundation . The authors would also like to thank Dr. M.S. Feather for his helpful advice in writing the English manuscript.
PY - 2014/4/25
Y1 - 2014/4/25
N2 - A disorder in the brain endothelium is thought to be closely related to the pathophysiology of brain diseases. A method for delivering nucleic acids (i.e. short interference RNA; siRNA) to the brain endothelium should be an attractive strategy for curing brain disorders. A liposomal nanoparticle containing a proton-ionizable amino lipid was recently developed as a carrier of encapsulated siRNA. The aim of this study was to evaluate the utility of apolipoprotein E (ApoE) as a targeting ligand for mouse brain endothelial cells (MBEC4 cells). The cellular uptake of the ApoE-modified nanoparticles was gradually increased in an ApoE-density dependent manner. Furthermore, the ApoE-modified nanoparticles were taken up via both clathrin and caveolae mediated endocytosis, thus permitting them to avoid lysosomal degradation. Finally, endogenous gene silencing in MBEC4 cells was efficiently achieved depending on the ApoE-modification. Collectively, the ApoE-modified nanoparticle is a promising carrier for delivering nucleic acids to the brain endothelium.
AB - A disorder in the brain endothelium is thought to be closely related to the pathophysiology of brain diseases. A method for delivering nucleic acids (i.e. short interference RNA; siRNA) to the brain endothelium should be an attractive strategy for curing brain disorders. A liposomal nanoparticle containing a proton-ionizable amino lipid was recently developed as a carrier of encapsulated siRNA. The aim of this study was to evaluate the utility of apolipoprotein E (ApoE) as a targeting ligand for mouse brain endothelial cells (MBEC4 cells). The cellular uptake of the ApoE-modified nanoparticles was gradually increased in an ApoE-density dependent manner. Furthermore, the ApoE-modified nanoparticles were taken up via both clathrin and caveolae mediated endocytosis, thus permitting them to avoid lysosomal degradation. Finally, endogenous gene silencing in MBEC4 cells was efficiently achieved depending on the ApoE-modification. Collectively, the ApoE-modified nanoparticle is a promising carrier for delivering nucleic acids to the brain endothelium.
KW - Apolipoprotein E (ApoE)
KW - Brain endothelial cell
KW - In vitro
KW - Multifunctional envelope-type nano device (MEND)
KW - YSK05
KW - siRNA delivery
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U2 - 10.1016/j.ijpharm.2014.02.016
DO - 10.1016/j.ijpharm.2014.02.016
M3 - Article
C2 - 24530390
AN - SCOPUS:84895538642
SN - 0378-5173
VL - 465
SP - 77
EP - 82
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -