No abstract

We have synthesized a series of MCM-41-type mesoporous silica nanoparticles (MSN). The surface of the MSNs are functionalized with 3-aminopropyl (AP), 3-guanidinopropyl (GP), 3-[N-(2-guanidinoethyl)guanidino]propyl (GEGP), and N-folate-3-aminopropyl (FAP). In contrast to the ζ-potential of −18.4 mV for FITC-MSN, the values of ζ-potential for AP-, GP-, GEGP-, and FAP-functionalized FITC-MSNs in 100 mM PBS buffer (pH 7.4) increased positively from −11.3, −10.6, −4.0, to +4.9 mV, respectively. The uptake efficiency, endocytosis mechanism, and biocompatibility of these organically functionalized MSNs were investigated with human cervical cancer cells (HeLa). Flow cytometry results suggested that the endocytosis of MSN could be manipulated by different surface functionalization. The immunocytochemistry study indicated that the uptake of these MSNs by HeLa cells was surface functional group dependent and involved several different mechanisms of endocytosis. Confocal fluorescence micrographs showed that the different surface functionalities of MSNs could also affect their ability to escape endosomal entrapment, which is a key factor in designing effective intracellular delivery vehicles.

Surface-functionalized silica nanoparticles can deliver DNA and drugs into animal cells and tissues. However, their use in plants is limited by the cell wall present in plant cells. Here we show a honeycomb mesoporous silica nanoparticle (MSN) system with 3-nm pores that can transport DNA and chemicals into isolated plant cells and intact leaves. We loaded the MSN with the gene and its chemical inducer and capped the ends with gold nanoparticles to keep the molecules from leaching out. Uncapping the gold nanoparticles released the chemicals and triggered gene expression in the plants under controlled-release conditions. Further developments such as pore enlargement and multifunctionalization of these MSNs may offer new possibilities in target-specific delivery of proteins, nucleotides and chemicals in plant biotechnology.

We synthesized a MCM-41-type mesoporous silica nanosphere (MSN)-based gene transfection system, where second generation (G2) polyamidoamines (PAMAMs) were covalently attached to the surface of MSN. The G2-PAMAM-capped MSN material (G2-MSN) was used to complex with a plasmid DNA (pEGFP-C1) that encodes for an enhanced green fluorescence protein. The gene transfection efficacy, uptake mechanism, and biocompatibility of the G2-MSN system with various cell types, such as neural glia (astrocytes), human cervical cancer (HeLa), and Chinese hamster ovarian (CHO) cells, were investigated. The mesoporous structure of the MSN material allows membrane-impermeable molecules, such as pharmaceutical drugs and fluorescent dyes, to be encapsulated inside the MSN channels. The system renders the possibility to serve as a universal transmembrane carrier for intracellular drug delivery and imaging applications.

The application of nanotechnology in the field of drug delivery has attracted much attention in the latest decades. Recent breakthroughs on the morphology control and surface functionalization of inorganic-based delivery vehicles, such as mesoporous silica nanoparticles (MSNs), have brought new possibilities to this burgeoning area of research. The ability to functionalize the surface of mesoporous-silica-based nanocarriers with stimuli-responsive groups, nanoparticles, polymers, and proteins that work as caps and gatekeepers for controlled release of various cargos is just one of the exciting results reported in the literature that highlights MSNs as a promising platform for various biotechnological and biomedical applications. This review focuses on the most recent progresses in the application of MSNs for intracellular drug delivery. The latest research on the pathways of entry into live mammalian and plant cells together with intracellular trafficking are described. One of the main areas of interest in this field is the development of site-specific drug delivery vehicles; the contribution of MSNs toward this topic is also summarized. In addition, the current research progress on the biocompatibility of this material in vitro and in vivo is discussed. Finally, the latest breakthroughs for intracellular controlled drug release using stimuli-responsive mesoporous-silica-based systems are described.

A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices.

The interactions of mesoporous silica nanoparticles (MSNs) of different particle sizes and surface properties with human red blood cell (RBC) membranes were investigated by membrane filtration, flow cytometry, and various microscopic techniques. Small MCM-41-type MSNs (∼100 nm) were found to adsorb to the surface of RBCs without disturbing the membrane or morphology. In contrast, adsorption of large SBA-15-type MSNs (∼600 nm) to RBCs induced a strong local membrane deformation leading to spiculation of RBCs, internalization of the particles, and eventual hemolysis. In addition, the relationship between the degree of MSN surface functionalization and the degree of its interaction with RBC, as well as the effect of RBC−MSN interaction on cellular deformability, were investigated. The results presented here provide a better understanding of the mechanisms of RBC−MSN interaction and the hemolytic activity of MSNs and will assist in the rational design of hemocompatible MSNs for intravenous drug delivery and in vivo imaging. R ecent advancements in particle size and morphology control of mesoporous materials have led to the creation of nano-and submicrometer-sized mesoporous silica nanoparticles (MSNs). [1][2][3][4][5] The MSN materials with well-ordered cylindrical pore structures, such as MCM-41 and SBA-15, have attracted special interest in the biomedical field. 1 The large surface areas and pore volumes of these materials allow the efficient adsorption of a wide range of molecules, including small drugs, 6-10 therapeutic proteins, 11-13 antibiotics, 14,15 and antibodies. 16 Therefore, these materials have been proposed for use as potential vehicles for biomedical imaging, real-time diagnosis, and controlled delivery of multiple therapeutic agents. [6][7][8]10,[17][18][19][20][21][22][23][24][25] Despite the considerable interest in the biomedical applications of MSNs, relatively few studies have been published on the biocompatibility of the two most common types of MSNs (MCM-41 and SBA-15). [26][27][28][29] Asefa and co-workers reported that the cellular bioenergetics (cellular respiration and ATP levels) were inhibited remarkably by large SBA-15 nanoparticles, but the inhibition was greatly reduced by smaller MCM-41-type nanoparticles. 26 These differences in the disruption of cellular bioenergetics are believed to be caused by the different surface areas, number of surface silanol groups, and/or particle sizes of both types of material. A recent study by Kohane and collaborators on the systemic effects of MCM-41 (particle size ∼150 nm) and SBA-15 (particle size ∼800 nm) MSNs in live animals revealed interesting findings regarding their biocompatibility. 27 While large doses of mesoporous silicas administered subcutaneously to mice appear to be relatively harmless, the same doses given intravenously or intraperitoneally were lethal. 27 A possible reason for the severe systemic toxicity of MSNs when injected intravenously could be the interactions of the nanoparticles with blood cells.Our initial studies...

The hemolytic properties of amorphous silica and MCM‐41‐type mesoporous silica nanoparticles (MSNs) with rabbit red blood cells (RBCs) are compared. The amorphous silica exhibits a high hemolytic activity toward the RBCs. In contrast, a high biocompatibility between the MSNs and the RBCs is observed. The low hemolytic activity of the MSNs offers promising potential for various in vivo biotechnological applications.