Luo Zhong, Hu Yan, Xin Renlong, Zhang Beilu, Li Jinghua, Ding Xingwei, Hou Yanhua, Yang Li, Cai Kaiyong
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, People's Republic of China; College of Material Science and Engineering, Chongqing University, Chongqing, 400044, People's Republic of China.
J Biomed Mater Res A. 2014 Nov;102(11):3781-94. doi: 10.1002/jbm.a.35049. Epub 2013 Dec 9.
Mesoporous silica nanoparticles (MSNs) present themselves as one of the most promising nano-carriers for drug delivery. To reduce their immunotoxicities, in this study, natural proteins of gelatin (Gel), bovine serum albumin (BSA), and lysozyme (Lys) were employed as end-caps of MSNs by using succinic anhydride as an intermediate linker, thus leading to fabrication of MSNs/protein nanocomposites, respectively. Furthermore, combined techniques of SEM, TEM, FTIR, and zeta potential instruments were utilized to monitor the construction processes of MSNs/protein nanocomposites, respectively. Finally, the immunotoxicities of those nanocomposites to macrophage cells (RAW264.7 cells) were investigated in detail, i.e., cell morphology, cell viability, nitric oxide (NO) production, reactive oxygen species (ROS), and acid phosphatase activity (ACP) as well as inflammation cytokine expressions (tumor necrosis factor-α and interleukin-1β). All results suggest that macrophages were activated after uptaking nanoparticles of SiO2 and MSNs, which subsequently induced severe inflammation responses in vitro. In contrast, the inflammation responses of MSNs nanocomposites were reduced dramatically after end-capping with those natural proteins. Overall, this study accumulates knowledge for the development of MSNs-based drug delivery systems with reduced immunotoxicity.
介孔二氧化硅纳米颗粒（MSNs）是最具潜力的药物递送纳米载体之一。为降低其免疫毒性，本研究以琥珀酸酐作为中间连接体，将明胶（Gel）、牛血清白蛋白（BSA）和溶菌酶（Lys）等天然蛋白质用作MSNs的封端剂，分别制备了MSNs/蛋白质纳米复合材料。此外，利用扫描电子显微镜（SEM）、透射电子显微镜（TEM）、傅里叶变换红外光谱仪（FTIR）和zeta电位仪等联用技术分别监测MSNs/蛋白质纳米复合材料的构建过程。最后，详细研究了这些纳米复合材料对巨噬细胞（RAW264.7细胞）的免疫毒性，即细胞形态、细胞活力、一氧化氮（NO）生成、活性氧（ROS）、酸性磷酸酶活性（ACP）以及炎症细胞因子表达（肿瘤坏死因子-α和白细胞介素-1β）。所有结果表明，巨噬细胞摄取二氧化硅纳米颗粒和MSNs后被激活，随后在体外诱导了严重的炎症反应。相比之下，用这些天然蛋白质封端后，MSNs纳米复合材料的炎症反应显著降低。总体而言，本研究为开发具有降低免疫毒性的基于MSNs的药物递送系统积累了知识。
