Kim Soo-Yeon, Lee Sang-Jin, Han Hyo-Kyung, Lim Soo-Jeong
Department of Integrative Bioscience and Bioengineering, Sejong University, Seoul, 98 Kunja-dong, Kwangjin-gu, Seoul 05006, Republic of Korea.
Genitourinary Cancer Branch, Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10408, Republic of Korea.
Acta Biomater. 2017 Feb;49:521-530. doi: 10.1016/j.actbio.2016.11.045. Epub 2016 Nov 18.
Electrostatic complexation of adenovirus (Ad) with cationic lipids or polymers has been shown to be an effective means for overcoming the limitations of adenoviral vectors and enhancing gene-transfer efficacy. However, such complexation causes cytotoxicity, limiting the use of this strategy. The present study explored the potential of 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) as a cationic vehicle for improving Ad-mediated gene transfer without inducing cytotoxicity. Aminoclay complexation produced a dose-dependent increase in Ad-mediated transgene expression in both Ad infection-sensitive and -refractory cells, thereby greatly lowering the Ad dose required for transgene expression. Unlike the case for cationic lipids (Lipofectamine) or polymers (Polybrene), the enhancement effect of aminoclay was not accompanied by significant cytotoxicity regardless of cell lines and it was not observed for nonviral plasmid vectors. Physical characterization studies revealed that nanobiohybrid complexes formed between aminoclay and Ad particles through electrostatic interactions, creating aggregates of Ad particles whose surface was shielded with aminoclay nanosheet oligomers. It appears that aminoclay complexation changes the surface charge of Ad particles from a negative to a highly positive value and thus increases Ad binding to cellular membranes, thereby providing an additional cellular entry mechanism, namely caveolae-dependent endocytosis. Aminoclay-Ad nanobiohybrids may serve as a next-generation efficient, versatile and biocompatible gene-delivery carrier.
Electrostatic complexation of adenovirus with cationic materials has been shown to be an effective means for enhancing gene-transfer efficacy in vitro. However, such complexation causes cytotoxicity, limiting the use of this strategy. The present study explored the potential of a synthesized organoclay 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) as a cationic vehicle for improving Ad-mediated gene transfer. Our data indicate that nanobiohybrid complexes form between aminoclay and Ad particles through electrostatic interactions, thereby greatly enhancing Ad-mediated gene transfer. Unlike the case for either cationic lipids or cationic polymers, the enhancement effect of aminoclay was not accompanied by significant cytotoxicity regardless of cell lines. Our findings in this work highlight that aminoclay-Ad nanobiohybrids may serve as a next-generation efficient and biocompatible gene-delivery carrier.
腺病毒（Ad）与阳离子脂质或聚合物的静电络合已被证明是克服腺病毒载体局限性并提高基因转移效率的有效手段。然而，这种络合会导致细胞毒性，限制了该策略的应用。本研究探索了3-氨丙基功能化镁叶硅酸盐（氨基粘土）作为阳离子载体在改善Ad介导的基因转移而不诱导细胞毒性方面的潜力。氨基粘土络合在Ad感染敏感和难治细胞中均使Ad介导的转基因表达呈剂量依赖性增加，从而大大降低了转基因表达所需的Ad剂量。与阳离子脂质（Lipofectamine）或聚合物（聚凝胺）不同，无论细胞系如何，氨基粘土的增强作用均未伴随明显的细胞毒性，并且非病毒质粒载体未观察到这种作用。物理表征研究表明，氨基粘土与Ad颗粒之间通过静电相互作用形成纳米生物杂交复合物，形成Ad颗粒聚集体，其表面被氨基粘土纳米片低聚物屏蔽。似乎氨基粘土络合将Ad颗粒的表面电荷从负值变为高度正值，从而增加Ad与细胞膜的结合，从而提供了一种额外的细胞进入机制，即小窝依赖的内吞作用。氨基粘土-Ad纳米生物杂交体可作为下一代高效、通用且生物相容的基因传递载体。
腺病毒与阳离子材料的静电络合已被证明是体外提高基因转移效率的有效手段。然而，这种络合会导致细胞毒性，限制了该策略的应用。本研究探索了合成的有机粘土3-氨丙基功能化镁叶硅酸盐（氨基粘土）作为阳离子载体在改善Ad介导的基因转移方面的潜力。我们的数据表明，氨基粘土与Ad颗粒之间通过静电相互作用形成纳米生物杂交复合物，从而大大增强了Ad介导的基因转移。与阳离子脂质或阳离子聚合物不同，无论细胞系如何，氨基粘土的增强作用均未伴随明显的细胞毒性。我们在这项工作中的发现突出表明，氨基粘土-Ad纳米生物杂交体可作为下一代高效且生物相容的基因传递载体。
