Chitosan-hyaluronic acid nanoparticles for gene silencing: The role of hyaluronic acid on the nanoparticles' formation and activity
Chitosan-hyaluronic acid nanoparticles for gene silencing: The role of hyaluronic acid on the nanoparticles' formation and activity
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DOI：
10.1016/j.colsurfb.2012.11.009
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发表时间：
2013-03-01
影响因子：
5.8
通讯作者：
Remunan-Lopez, Carmen
中科院分区：
文献类型：
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作者：
Al-Qadi, Sonia;Alatorre-Meda, Manuel;Remunan-Lopez, Carmen
透明质酸 (HA) 被描述为基因传递系统的生物相容性增强剂；然而，人们对它的包含对此类系统的形成和活性以及随后的基因释放的机制影响知之甚少。为了更好地理解这些问题，我们在此描述了用于基因沉默的壳聚糖和壳聚糖-透明质酸纳米颗粒（CS 和 CS:HA NP）的制备和表征。通过离子凝胶化制备了不同的制剂，并评估了它们在 A549-Luc 细胞中的理化性质和生物活性。与 CS NP 相比，将 HA 添加到 CS NP 中可产生与 Lipofectamine (TM) RNAiMAX 相当的沉默活性（约 85% 的荧光素酶敲低），并显着提高细胞活力。如等温滴定量热法所示，HA 与 siRNA 竞争 CS 结合，使 CS-siRNA 结合强度降低 25%。这表明除了改善 CS NP 的细胞生物相容性外，HA 还可能通过放松 CS-siRNA 结合来促进其基因释放。 (C) 2012 Elsevier B.V. 保留所有权利。
Hyaluronic acid (HA) has been described as a biocompatibility enhancer for gene delivery systems; however, the mechanistic implications of its inclusion on the formation and activity of such systems and subsequent gene release are poorly understood. To better understand these issues, we describe herein the preparation and characterization of chitosan and chitosan-hyaluronic acid nanoparticles (CS and CS:HA NPs) for gene silencing. Different formulations were prepared by ionotropic gelation and evaluated for their physicochemical properties and biological activities in A549-Luc cells. Inclusion of HA to CS NPs resulted in a comparable silencing activity with Lipofectamine (TM) RNAiMAX (approximate to 85% of luciferase knockdown) and significantly improved cell viability compared with CS NPs. As depicted by isothermal titration calorimetry, HA competed with siRNA for CS binding, lowering CS-siRNA binding strength by 25%. This suggests that besides improving cell biocompatibility of CS NPs, HA might also promote their gene release by loosening the CS-siRNA binding. (C) 2012 Elsevier B.V. All rights reserved.