Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing.
The development of a tumor-specific immunoliposome delivering small interfering RNA (siRNA) represents a practical way in cancer gene therapy. In this study, we developed PEGylated 3beta-[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol)/dioleoylphosphatidyl ethanolamine (DOPE) immunoliposomes conjugated with the Fab' of recombinant humanized anti-HER2 monoclonal antibody (PIL) for siRNA delivery. The results demonstrated that the lyophilized PIL (LPIL) prepared by the lyophilization/rehydration method possessed a significantly enhanced HER1 gene, a model target, silencing ability compared with PIL in HER2-overexpressing SK-BR3 cells. Among a series of LPIL with different PEGylation degree, LPIL containing 2.5%PEG (2.5%PEG LPIL) showed the best HER1 gene silencing activity. Confocal microscope studies demonstrated that 2.5%PEG LPIL could specifically bind to SK-BR3 cells and were sequentially internalized into them. Using RhoA as a cancer therapeutic target, 2.5%PEG LPIL entrapping anti-RhoA siRNA could specifically silence RhoA expression and inhibit cell invasion in SK-BR3 cells. In conclusion, these finding demonstrated the potential use of 2.5%PEG LPIL in specifically delivering siRNA to HER2-overexpressing cancers.
Gao
Jie
J
International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, PR China.
Sun
Jing
J
Li
Huimei
H
Liu
Wei
W
Zhang
Yang
Y
Li
Bohua
B
Qian
Weizhu
W
Wang
Hao
H
Chen
Jianming
J
Guo
Yajun
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D005612:Freeze Drying; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000378:metabolism*; D020871:RNA Stability / Q000187:drug effects; D034741:RNA, Small Interfering / Q000097:blood / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000911:Antibodies, Monoclonal; D002784:Cholesterol; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D011092:Polyethylene Glycols; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D020742:rhoA GTP-Binding Protein; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C508053:ERBB2 protein, human