Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing

The development of a tumor-specific immunolipsome delivering small interfering RNA (siRNA) represents a practical way in cancer gene therapy In this study. we developed PEGylated 3 beta-[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 HER] 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 HERI 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 Ill Conclusion. these finding demonstrated the potential use of 2 5%PEG LPIL in specifically delivering siRNA to HER2-overexpressing cancers (C) 2009 Elsevier Ltd All rights reserved