For the purpose of increasing the in vivo stability of polycation gene carriers, we prepared a kind of p H-sensitive poly（ethylene glycol）-poly（γ-benzyl-L-glutamate-co-glutamic acid）（PEG-PGA（65）, 65 denotes th...For the purpose of increasing the in vivo stability of polycation gene carriers, we prepared a kind of p H-sensitive poly（ethylene glycol）-poly（γ-benzyl-L-glutamate-co-glutamic acid）（PEG-PGA（65）, 65 denotes the molar ratio of glutamic acid in poly（γ-benzyl-L-glutamate-co-glutamic acid））. PEG-PGA（65） showed low cytotoxicity and could shield the positive charge of DNA/PEI（1：1） polyplexes efficiently. The transfection was enhanced due to the partially charge shielding in He La cell line at pH of 7.4. There was almost no transfection efficiency when the surface charge of the ternary particles turned to negative at p H of 7.4. However, the transfection efficiency recovered a lot by culturing at p H of 6.0 at the beginning of transfection. Confocal microscopic observation and flow cytometry results showed DNA/PEI polyplexes should be efficiently released and endocytosized at p H 6.0, because of the p H triggered deshielding action of PEG-PGA（65）. Due to the good biocompatibility and suitable p H triggered shielding/deshielding property, PEG-PGA（65） could be a potential shielding system for polycationic gene carriers used in vivo.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.51203132,51222307,51303173,51390484,21474104 and 51403205)Natural Science Foundation of Guangdong Province,China(S2012040008070)Foundation for Distinguished Young Talents in Higher Education of Guangdong,China(2012LYM_0093)
文摘For the purpose of increasing the in vivo stability of polycation gene carriers, we prepared a kind of p H-sensitive poly（ethylene glycol）-poly（γ-benzyl-L-glutamate-co-glutamic acid）（PEG-PGA（65）, 65 denotes the molar ratio of glutamic acid in poly（γ-benzyl-L-glutamate-co-glutamic acid））. PEG-PGA（65） showed low cytotoxicity and could shield the positive charge of DNA/PEI（1：1） polyplexes efficiently. The transfection was enhanced due to the partially charge shielding in He La cell line at pH of 7.4. There was almost no transfection efficiency when the surface charge of the ternary particles turned to negative at p H of 7.4. However, the transfection efficiency recovered a lot by culturing at p H of 6.0 at the beginning of transfection. Confocal microscopic observation and flow cytometry results showed DNA/PEI polyplexes should be efficiently released and endocytosized at p H 6.0, because of the p H triggered deshielding action of PEG-PGA（65）. Due to the good biocompatibility and suitable p H triggered shielding/deshielding property, PEG-PGA（65） could be a potential shielding system for polycationic gene carriers used in vivo.
