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

机译:使用咔蛋白氧化物进行Dendron缀合物,以便使用咔哒化学以获得有效的基因递送

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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) π–π 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:由于其大表面积和快速的细胞摄取,氧化石墨烯(GO)作为一种有吸引力的候选材料,用于递送药物和基因。 Go的固有的SP〜(2)π-π相互作用有助于携带药物和单链RNA(SSRNA),但没有与双链DNA(DSDNA)相互作用。在这项工作中,通过“点击”化学将聚酰胺胺(PAMAM)树枝状(PAMAM)树状组缀合,以改善去的DNA络合能力以及其转染效率。在具有阳性Zeta电位的阳性Zeta电位后,去产生球形纳米颗粒(250-350nm)颗粒的颗粒化(250-350nm)颗粒后,DNA络合能力显着提高。在PAMAM DENDRON的共轭后,转染效率显着增加。观察到具有80%的细胞活力的HeLa细胞中51%的转染效率。转染效率显着高于聚乙烯亚胺25kDA(效率为27%),并且还超越了Lipofectamine 2000(效率47%)。 Caveolae介导的内吞作用途径的DGO / PDNA复合物的摄取可能会显着促进高转染效率。因此,Dendronized Go被显示为具有最小毒性的有效基因载体,并且是用作基因治疗的非毒性载体的有希望的候选者。

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