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用于免疫刺激型CpG寡脱氧核苷酸细胞内递送的氧化石墨烯-壳聚糖纳米复合材料

Graphene oxide-chitosan nanocomposites for intracellular delivery of immunostimulatory CpG oligodeoxynucleotides.

作者信息

Zhang Huijie, Yan Ting, Xu Sha, Feng Shini, Huang Dandi, Fujita Morihisa, Gao Xiao-Dong

机构信息

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Apr 1;73:144-151. doi: 10.1016/j.msec.2016.12.072. Epub 2016 Dec 18.

DOI:10.1016/j.msec.2016.12.072
PMID:28183591
Abstract

CpG oligodeoxynucleotides (ODNs) activate innate and adaptive immune responses, and show strong potential as immunotherapeutic agents against various diseases. Benefiting from their unique physicochemical properties, graphene oxide (GO) has recently attracted great attention in nanomedicine. In this study, we developed a novel CpG ODNs delivery system based on GO-chitosan (GO-CS) nanocomposites. GO-CS nanocomposites were prepared by self-assembly of both components via electrostatic interactions. Compared with GO, GO-CS nanocomposites possessed smaller size, positive surface charge and lower cytotoxicity. CpG ODNs were loaded onto GO-CS nanocomposites via electrostatic interactions. GO-CS nanocomposites greatly improved the loading capacity and cellular uptake of CpG ODNs. GO-CS/CpG ODNs complexes further resulted in an enhanced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production compared with that of free CpG ODNs and GO/CpG ODNs complexes. Therefore, GO-CS nanocomposites can serve as efficient nanocarriers for enhancing the delivery efficiency of CpG ODNs.

摘要

CpG 寡脱氧核苷酸(ODNs)可激活先天性和适应性免疫反应,作为针对各种疾病的免疫治疗药物具有强大潜力。氧化石墨烯(GO)因其独特的物理化学性质,近年来在纳米医学领域备受关注。在本研究中,我们开发了一种基于氧化石墨烯-壳聚糖(GO-CS)纳米复合材料的新型 CpG ODNs 递送系统。GO-CS 纳米复合材料通过两种成分通过静电相互作用自组装制备而成。与 GO 相比,GO-CS 纳米复合材料尺寸更小、表面带正电荷且细胞毒性更低。CpG ODNs 通过静电相互作用负载到 GO-CS 纳米复合材料上。GO-CS 纳米复合材料极大地提高了 CpG ODNs 的负载能力和细胞摄取量。与游离 CpG ODNs 和 GO/CpG ODNs 复合物相比,GO-CS/CpG ODNs 复合物进一步导致白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的产生增加。因此,GO-CS 纳米复合材料可作为高效纳米载体,用于提高 CpG ODNs 的递送效率。

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