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首页> 外文期刊>ACS applied materials & interfaces >Complex Coacervation-Integrated Hybrid Nanoparticles Increasing Plasmid DNA Delivery Efficiency in Vivo
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Complex Coacervation-Integrated Hybrid Nanoparticles Increasing Plasmid DNA Delivery Efficiency in Vivo

机译：复杂凝聚整合杂交纳米粒子提高体内质粒DNA的传递效率。

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Many polycation-based gene delivery vehicles have limited in vivo transfection efficiency because of their excessive exterior positive charges and/or PEGylation, both of which could result in premature dissociation and poor cellular uptake and trafficking. Here, we reported novel hybrid PEGylated nanoparticles (HNPs) that are composed of (a) poly(ethylene glycol)-b-poly(aspartate)-adamantane (PEG-P(asp)-Ad) constituting the outer PEG layer to provide colloidal stability; (b) poly(ethylenimine)(10K) (PEI10K) forming complex coacervate with P(asp) as the cross-linked cage preventing premature dissociation; (c) cyclodextrin-decorated PEI10K (PEI10K-CD) forming the core with reporter plasmid DNA (pDNA). These HNPs exhibited an increased stability and higher in vitro transfection efficiency compared to traditional PEGylated nanoparticles (PEG-NP). Intratumoral injections further demonstrated that HNPs were able to successfully deliver pDNAs into tumors, while PEG-NP and PEI25K had only negligible delivery efficiencies. Moreover, HNPs' in vivo stability and pDNA delivery capability post intravenous injection were also confirmed by live animal bioluminescence and fluorescence image analysis. It is likely that the coacervation integration at the interface of PEI10K-CD/pDNA core and the PEG shell attributed to the significantly improved in vivo transfection efficiency of HNPs over PEG-NP and PEI25K. This study suggests that the HNP has the potential for in vivo gene delivery applications with significantly improved gene transfection efficiency.
机译：许多基于聚阳离子的基因递送载体由于其过量的外部正电荷和/或PEG化而使其体内转染效率受到限制，这两者都可能导致过早解离以及不良的细胞摄取和运输。在这里，我们报告了新颖的杂化PEG化纳米颗粒（HNP），它由构成外PEG层以提供胶体的（a）聚（乙二醇）-b-聚（天冬氨酸）-金刚烷（PEG-P（asp）-Ad）组成稳定性; （b）聚（乙烯亚胺）（10K）（PEI10K）与P（asp）形成复合凝聚层，作为交联笼，防止过早解离; （c）环糊精修饰的PEI10K（PEI10K-CD）与报告质粒DNA（pDNA）形成核心。与传统的PEG化纳米颗粒（PEG-NP）相比，这些HNP表现出更高的稳定性和更高的体外转染效率。肿瘤内注射进一步证明，HNPs能够成功地将pDNAs传递到肿瘤中，而PEG-NP和PEI25K的传递效率却可以忽略不计。此外，活动物的生物发光和荧光图像分析也证实了静脉注射后HNP的体内稳定性和pDNA传递能力。 PEI10K-CD / pDNA核心与PEG外壳之间的凝聚凝聚很可能归因于HNP的体内转染效率明显高于PEG-NP和PEI25K。这项研究表明，HNP具有潜在的体内基因传递应用潜力，可显着提高基因转染效率。

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