Encapsulation of PEGylated low-molecular-weight PEI polyplexes in hyaluronic acid hydrogels reduces aggregation.
Encapsulation of PEGylated low-molecular-weight PEI polyplexes in hyaluronic acid hydrogels reduces aggregation.
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DOI：
10.1016/j.actbio.2015.09.020
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发表时间：
2015-12
影响因子：
9.7
通讯作者：
Segura T
中科院分区：
文献类型：
--
作者：
Siegman S;Truong NF;Segura T
DNA的有效局部递送可以增加基因治疗在组织再生和治疗性血管生成中的适用性。一种有前途的方法是通过使用多孔水凝胶支架，将DNA以纳米颗粒的形式掺入并递送到受影响的部位。虽然我们之前已经报道了笼状纳米颗粒封装（CnE）以在水凝胶内以高浓度加载DNA聚合复合物而不聚集，但是在CnE之后已经遇到了有限的聚合复合物释放的常见问题。在这项研究中，我们报告了两种替代的方法，以减少聚合物在多孔水凝胶中的聚集。第一种方法通过利用基因载体聚合物聚乙烯亚胺（sPEG-PEI）的聚乙二醇修饰来减少聚合复合物聚集，以减轻凝胶化期间聚合复合物与支架之间的电荷-电荷相互作用。第二种方法静电呈现在支架孔的表面上的复合物，而不是封装的呈现。与传统使用的线性PEI（LPEI）聚合物相比，sPEG-PEI聚合物形成更小、毒性更低且更稳定的聚合复合物，其在HA凝胶内表现出更少的聚集。表面涂覆的聚合复合物也导致聚合复合物在水凝胶中更均匀的分布。此外，sPEG-PEI复合物在3D表面包被的转染中保留了与LPEI相当的转染能力。这些结果表明，在支架介导的基因传递的显着改善，并显示在多基因传递系统的应用前景。
The effective delivery of DNA locally could increase the applicability of gene therapy in tissue regeneration and therapeutic angiogenesis. One promising approach is through use of porous hydrogel scaffolds that incorporate and deliver DNA in the form of nanoparticles to the affected sites. While we have previously reported on Caged nanoparticle Encapsulation (CnE) to load DNA polyplexes within hydrogels at high concentrations without aggregation, frequent issues with limited polyplex release following CnE have been encountered. In this study, we report two alternative approaches to polyplex presentation for decreasing aggregation in porous hydrogels. The first approach reduces polyplex aggregation by utilizing polyethylene glycol modification of the gene carrier polymer polyethyleneimine (sPEG-PEI) to mitigate charge-charge interactions between polyplexes and the scaffold during gelation. The second approach electrostatically presents polyplexes on the surfaces of scaffold pores as opposed to an encapsulated presentation. The sPEG-PEI polymer formed a smaller, less toxic, and more stable polyplex that exhibited less aggregation within HA gels when compared to the traditionally used linear PEI (LPEI) polymer. Surface-coated polyplexes also resulted in a more homogenous distribution of polyplexes in hydrogels. Furthermore, sPEG-PEI polyplexes retained transfection abilities comparable to LPEI in 3D surface-coated transfections. These results demonstrate a significant improvement in scaffold-mediated gene delivery and show promise in applications to multi-gene delivery systems.