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含高浓度 DNA/PEI 聚集体的透明质酸和纤维蛋白水凝胶用于局部基因递送。

Hyaluronic acid and fibrin hydrogels with concentrated DNA/PEI polyplexes for local gene delivery.

机构信息

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 420 Westwood Plaza, BH5531, Los Angeles, CA 90095, USA.

出版信息

J Control Release. 2011 Aug 10;153(3):255-61. doi: 10.1016/j.jconrel.2011.01.028. Epub 2011 Feb 2.

Abstract

Local delivery of DNA through a hydrogel scaffold would increase the applicability of gene therapy in tissue regeneration and cancer therapy. However, the delivery of DNA/cationic polymer nanoparticles (polyplexes) using hydrogels is challenging due to the aggregation and inactivation of polyplexes during their incorporation into hydrogel scaffolds. We developed a novel process (termed caged nanoparticle encapsulation or CnE) to load concentrated and unaggregated non-viral gene delivery nanoparticles into various hydrogels. Previously, we showed that PEG hydrogels loaded with DNA/PEI polyplexes through this process were able to deliver genes both in vitro and in vivo. In this study, we found that hyaluronic acid and fibrin hydrogels with concentrated and unaggregated polyplexes loaded through CnE were able to deliver genes in vivo as well, demonstrating the universality of the process.

摘要

通过水凝胶支架进行局部 DNA 递送将增加基因治疗在组织再生和癌症治疗中的适用性。然而,由于 DNA/阳离子聚合物纳米颗粒(聚合物)在掺入水凝胶支架过程中的聚集和失活,使用水凝胶进行 DNA 递送具有挑战性。我们开发了一种新的方法(称为笼状纳米颗粒包封或 CnE),将浓缩且未聚集的非病毒基因传递纳米颗粒加载到各种水凝胶中。此前,我们表明,通过该方法将 DNA/PEI 聚合物纳米颗粒载入聚乙二醇水凝胶中,无论是在体外还是体内,都能够递送基因。在这项研究中,我们发现,通过 CnE 载入浓缩且未聚集的聚合物纳米颗粒的透明质酸和纤维蛋白水凝胶也能够在体内递送基因,证明了该方法的普遍性。

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