Surface functionalized mesoporous silica nanoparticles with natural proteins for reduced immunotoxicity

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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3781–3794, 2014.