Hyaluronic acid hydrogel scaffolds loaded with cationic niosomes for efficient non-viral gene delivery.
Hyaluronic acid hydrogel scaffolds loaded with cationic niosomes for efficient non-viral gene delivery.
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DOI：
10.1039/c8ra05125a
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发表时间：
2018-09-17
期刊：
影响因子：
3.9
通讯作者：
Segura T
中科院分区：
文献类型：
--
作者：
Villate-Beitia I;Truong NF;Gallego I;Zárate J;Puras G;Pedraz JL;Segura T
理想的非病毒基因载体的缺乏促使了递送系统和组织工程支架的结合，这可能提供相关的优势，如增强稳定性和降低毒性。在这项工作中，我们评估了niosome非病毒载体和透明质酸（HA）水凝胶支架之间的新组合，两者都因其生物相容性以及结合多种分子的能力而被广泛研究。我们评估了三种不同的乳质体配方（乳质体1、2和3）在阳离子脂质、辅助脂质和非离子张力活性成分上的变化。通过添加质粒DNA获得的Niosomes和nioplexes的大小、多分散性、zeta电位以及在2D培养中转染小鼠骨髓克隆间充质干细胞（mMSCs）的能力进行了表征。由于Niosome 1具有较高的转染效率，因此选择将其包封在HA水凝胶中，并且为了能够在HA水凝胶中掺入更多的DNA，对配方进行了浓缩。负载nioplex的HA水凝胶在生物力学性能、颗粒分布、nioplex释放动力学以及在3D培养中转染被封装的mMSCs的能力方面进行了表征。我们的研究结果表明，负载nioplex的HA水凝胶支架很少或没有颗粒聚集，允许广泛的细胞扩散，并且能够有效地转染具有高细胞活力的被封装的mMSCs。我们相信，通过这种体外模型获得的知识可以用于设计新颖有效的体内局部和非病毒基因传递应用平台。包裹在透明质酸水凝胶支架中的Nioplexes没有颗粒聚集，含有大量的DNA，允许广泛的细胞扩散，并且能够在具有高细胞活力的3D培养中有效地转染间充质干细胞。
The lack of ideal non-viral gene carriers has motivated the combination of delivery systems and tissue-engineered scaffolds, which may offer relevant advantages such as enhanced stability and reduced toxicity. In this work, we evaluated a new combination between niosome non-viral vectors and hyaluronic acid (HA) hydrogel scaffolds, both widely studied due to their biocompatibility as well as their ability to incorporate a wide variety of molecules. We evaluated three different niosome formulations (niosomes 1, 2 and 3) varying in composition of cationic lipid, helper lipid and non-ionic tensioactives. Niosomes and nioplexes obtained upon the addition of plasmid DNA were characterized in terms of size, polydispersity, zeta potential and ability to transfect mouse bone marrow cloned mesenchymal stem cells (mMSCs) in 2D culture. Niosome 1 was selected for encapsulation in HA hydrogels due to its higher transfection efficiency and the formulation was concentrated in order to be able to incorporate higher amounts of DNA within HA hydrogels. Nioplex-loaded HA hydrogels were characterized in terms of biomechanical properties, particle distribution, nioplex release kinetics and ability to transfect encapsulated mMSCs in 3D culture. Our results showed that nioplex-loaded HA hydrogel scaffolds presented little or no particle aggregation, allowed for extensive cell spreading and were able to efficiently transfect encapsulated mMSCs with high cellular viability. We believe that the knowledge gained through this in vitro model can be utilized to design novel and effective platforms for in vivo local and non-viral gene delivery applications. Nioplexes encapsulated in HA hydrogel scaffolds present no particle aggregation, incorporate high amount of DNA, allow extensive cell spreading and are able to efficiently transfect mesenchymal stem cells in 3D cultures with high cellular viability.
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