Efficacious Gene Silencing in Serum and Significant Apoptotic Activity Induction by Survivin Downregulation Mediated by New Cationic Gemini Tocopheryl Lipids

作者: Krishan Kumar , Bappa Maiti , Paturu Kondaiah , Santanu Bhattacharya

DOI: 10.1021/MP500620E

关键词:

摘要: Nonviral gene delivery offers cationic liposomes as promising instruments for the of double-stranded RNA (ds RNA) molecules successful sequence-specific silencing (RNA interference). The efficient siRNA (small interfering to cells while avoiding unexpected side effects is an important prerequisite exploitation power this excellent tool. We present here six new tocopherol based gemini lipids, which induce substantial knockdown without any obvious cytotoxicity. All coliposomal formulations derived from each these geminis and a helper lipid, dioleoylphosphatidylethanolamine (DOPE), were well characterized using physical methods such atomic force microscopy (AFM) dynamic light scattering (DLS). Zeta potential measurements conducted estimate surface charge formulations. Flow cytometric analysis showed that optimized could transfect anti-GFP efficiently in three different GFP expressing cell lines, viz., HEK 293T, HeLa, Caco-2, significantly better than potent commercial standard Lipofectamine 2000 (L2K) both absence presence serum (FBS). Notably, activity coliposomes lipids was not affected even (10% 50% FBS) it dropped down L2K significantly. Observations under fluorescence microscope, RT-PCR, Western blot substantiated flow cytometry results. cellular entry labeled evidenced confocal put forward among lipidic carriers siRNA. transfection capabilities also profiled more relevant fashion performing transfections against survivin (an anti-apoptotic protein) induced apoptosis. Furthermore, downregulation improved therapeutic efficacy levels anticancer drug, doxorubicin, In short, appear be highly achieving mediated various lines.

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