The comparative effects of mesoporous silica nanoparticles and colloidal silica on inflammation and apoptosis
Introduction
With the growing progress of nanotechnology in biomedical applications, the use of nanomaterials as biomaterials has received considerable attention in both fundamental and technological developments [1], [2]. Meanwhile, the unique physicochemical characteristics of nanomaterials raised concerns about their potential environmental and health impacts [3]. Current in vitro studies showed different ways in which nanomaterials could influence biological functions or induce cytotoxicity [4], [5]. Because the physicochemical properties of nanoparticles are different from those of their bulk counterparts, their interaction with biological systems is expected to be different. Specifically, following accidental or intentional exposure, nanomaterials may stimulate and/or suppress the immune responses [6]. The use of nanomaterials in biomedical fields is likely to result in interactions between these materials and immune-competent cells, which are desirable for some applications, but may also trigger unwanted effects [7].
Many immunotoxic effects were shown to be due to interference with components of the signaling pathways involved in activation of the immune response, in particular with the mitogen-activated protein kinases (MAPKs) [8]. MAPKs are a group of oxidant-dependent signaling molecules potentially important in nanomaterial-induced inflammation and proliferative responses [9]. The MAPK signaling pathway has been shown to play a role in nuclear factor (NF)-κB activation through serine phosphorylation of IκB-α, leading to degradation of IκB-α [10]. NF-κB controls a variety of genes involved in immune, inflammatory, and proliferative responses; these include various pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and cell-adhesion molecules [11].
The effects of nanomaterials on cells may vary with different conditions of nanomaterials, depending on their chemical composition, crystallinity, size, shape and surface area [12]. Mesoporous silica (MPS), synthesized via the supramolecular polymer templating method, is one of the important members of nanomaterials in biomedical fields. MPS are a special class of synthetically modified colloidal silica, in which highly ordered pores in the meso-scale (2–50 nm) are introduced. MPS have received enormous attention in various biomedical applications, such as drug-/protein-/gene-delivery, labeling, bioseparation, transfection device, and tissue engineering, because of their unique pore architecture, that is, large specific surface area, pore volume, and controllable pore size [13], [14], [15]. Silica is generally considered to be non-cytotoxic [12]. However, development of MPS nanoparticles for biomedical use requires close attention to safety issues, because extremely high surface area of MPS could exert different effects on human health and environment. Previous studies concerning biocompatibility of MPS investigated the general conditions of nanomaterials, such as size, surface charge, and morphology [16], [17], [18], [19], [20]. The surface area of nanomaterials may also greatly affect on biocompatibility due to high reactivity. However, in spite of the extraordinary high surface area of MPS nanoparticles, no information regarding the effect of surface area on biocompatibility has been discussed. In this study, we first examined the effect of MPS nanoparticles on the cytotoxicity and the relationship between pore structural properties (surface area) and the biological response, as compared with colloidal silica nanoparticles in macrophages.
Section snippets
Materials
Cetyltrimethyl-ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), ammonium hydroxide, HCl, ethanol, and methanol were purchased from Sigma–Aldrich (St. Louis, MO), and were used without further purification. Fluorescent probes, propidium iodide (PI) and Annexin V, were procured from Molecular Probes (Eugene, OR). PD98059, SB203580, SP600125, and pyrrolidine dithiocarbamate (PDTC) were purchased from Calbiochem (La Jolla, CA).
Nanoparticle preparation
MPS and colloidal silica nanoparticles were prepared using a
Characterization of materials
FE-SEM images of colloidal silica (Fig. 1A) and MPS (Fig. 1B) indicate that both nanoparticles showed same morphology (as spherical), with diameters in about 100 nm, and were well discrete. A hexagonally well-ordered mesostructure, with the average pore size of 2.4 nm, were observed by TEM observation in MPS (Fig. 1B inset), while no pore structure was observed in colloidal silica (Fig. 1A inset and SI. 1). CTAB used as polymer template was well removed by solvent extraction process (SI. 2).
Discussion
MPS nanoparticles have been widely investigated in the field of drug delivery, drug targeting, tissue engineering, gene transfection and cell tracking [12], [17], [27], [28], [29], [30]. The unique mesoporous structure of these particles is the cause for the broad interest in their application in biotechnology. Their large internal volumes and high surface areas allow for high adsorption of drugs and proteins into their structures [31]. However, the biological response to these materials has
Conclusions
We demonstrated the effect of pore structural conditions of silica nanoparticles on inflammation and apoptosis, and defined underlying mechanisms of action. Mesoporous silica nanoparticle, MPS, with high porosity induced the reduction of in vitro cytotoxicity and inflammation compared with non-porous silica nanoparticle, colloidal silica. The less activation of MAPKs, NF-κB, and caspase 3 by MPS is apparently responsible for the decrease of toxicity and expression of pro-inflammatory cytokines.
Acknowledgments
This work was supported by the Mid-career Researcher Program through an NRF grant funded by the MEST (No. 2010-0027969 and No. 2011-0017572) and by the Grant of the Korean Ministry of Education, Science and Technology (The Regional Core Research Program/Anti-aging and Well-being Research Center).
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