Hyaluronic acid and fibrin hydrogels with concentrated DNA/PEI polyplexes for local gene delivery.
Hyaluronic acid and fibrin hydrogels with concentrated DNA/PEI polyplexes for local gene delivery.
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DOI：
10.1016/j.jconrel.2011.01.028
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发表时间：
2011-08-10
期刊：
影响因子：
--
通讯作者：
Segura T
中科院分区：
文献类型：
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作者：
Lei Y;Rahim M;Ng Q;Segura T
通过水凝胶支架局部递送 DNA 将增加基因治疗在组织再生和癌症治疗中的适用性。然而，使用水凝胶递送DNA/阳离子聚合物纳米颗粒（聚合物复合物）具有挑战性，因为聚合物复合物在掺入水凝胶支架期间会发生聚集和失活。我们开发了一种新工艺（称为笼式纳米颗粒封装或 CnE），将浓缩和未聚集的非病毒基因递送纳米颗粒加载到各种水凝胶中。之前，我们证明通过这一过程装载 DNA/PEI 复合物的 PEG 水凝胶能够在体外和体内传递基因。在这项研究中，我们发现通过 CnE 加载的具有浓缩和未聚集复合物的透明质酸和纤维蛋白水凝胶也能够在体内传递基因，证明了该过程的普遍性。
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.