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Biomaterials

Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing.


PMID 20035999

Abstract

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.

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92243
Cholesteryl N-(2-dimethylaminoethyl)carbamate, ≥98% (TLC)
C32H56N2O2