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Dendron conjugation to graphene oxide using click chemistry for efficient gene delivery

机译:使用点击化学将Dendron与氧化石墨烯共轭以有效地传递基因

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Owing to its large surface area and rapid cellular uptake, graphene oxide (GO) is emerging as an attractive candidate material for delivery of drugs and genes. The inherent sp(2) pi-pi interaction of GO helps to carry drugs and single stranded RNA (ssRNA) but there is no such interaction with double stranded DNA (dsDNA). In this work, a polyamidoamine (PAMAM) dendron was conjugated with nano GO (nGO) through "click" chemistry to improve the DNA complexation capability of GO as well as its transfection efficiency. The DNA complexation capability of GO was significantly enhanced after dendronization of GO yielding spherical nanosized (250-350 nm) particles of the dendronized GO (DGO)/pDNA complex with a positive zeta potential. The transfection efficiency of GO dramatically increased after conjugation of the PAMAM dendron. Transfection efficiency of 51% in HeLa cells with cell viability of 80% was observed. The transfection efficiency was significantly higher than that of polyethyleneimine 25 kDa (27% efficiency) and also surpassed that of lipofectamine 2000 (47% efficiency). The uptake of the DGO/pDNA complex by the caveolae mediated endocytosis pathway may significantly contribute to the high transfection efficiency. Thus, dendronized GO is shown to be an efficient gene carrier with minimal toxicity and is a promising candidate for use as a nonviral carrier for gene therapy.
机译:由于其大的表面积和快速的细胞吸收,氧化石墨烯(GO)正在成为一种有吸引力的候选药物和基因传递材料。 GO固有的sp(2)pi-pi相互作用有助于携带药物和单链RNA(ssRNA),但与双链DNA(dsDNA)没有这种相互作用。在这项工作中,通过“点击”化学将聚酰胺酰氨基(PAMAM)树突与纳米GO(nGO)偶联,以提高GO的DNA络合能力及其转染效率。 GO的树突化后,GO的DNA络合能力得到了显着增强,产生了具有正Zeta电位的树突化的GO(DGO)/ pDNA复合物球形纳米(250-350 nm)颗粒。结合PAMAM树突后,GO的转染效率显着提高。观察到HeLa细胞的转染效率为51%,细胞活力为80%。转染效率显着高于25kDa的聚乙烯亚胺(27%的效率),也超过了lipofectamine 2000(47%的效率)。小窝介导的胞吞途径对DGO / pDNA复合物的摄取可能显着有助于高转染效率。因此,树突化的GO被证明是具有最小毒性的有效基因载体,并且有望用作基因治疗的非病毒载体。

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