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.
Recent applications of inorganic nanomaterials in the field of drug delivery have attracted a lot of attention in the last decade. One of the most promising candidates for this matter is mesoporous silica nanoparticles. This review highlights the latest progress in terms of the application of mesoporous silica nanoparticles for intracellular drug delivery.
A gold nanoparticle (AuNP)-capped mesoporous silica nanosphere (MSN)-based intracellular drug delivery system (PR-AuNPs-MSN) for the photoinduced controlled release of an anticancer drug, paclitaxel, ...inside of human fibroblast and liver cells was synthesized and characterized. We found that the mesopores of MSN could be efficiently capped by the photoresponsive AuNPs without leaking the toxic drug, paclitaxel, inside of live human cells. This "zero premature release" characteristic is of importance for delivery of toxic drugs in chemotherapy. Furthermore, we demonstrated that the cargo-release property of this PR-AuNPs-MSN system could be easily controlled by low-power photoirradiation under biocompatible and physiological conditions. We envision that our results would play a significant role in designing new generations of carrier materials for intracellular delivery of a variety of hydrophobic toxic drugs.
Peaceful coexistence: Brønsted acids and bases were attached to different surfaces of a mesoporous silica nanoparticle. The internal surface was functionalized by using co‐condensation, and ...postsynthesis grafting was used to functionalize the external surface. A two‐step reaction sequence that cannot proceed with an acid and base in the same pot was accomplished using the bifunctionalized nanoparticle (see scheme).
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.
In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis ...of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.
An MCM-41-type mesoporous silica nanoparticle (MSN) material with a large average pore diameter (5.4 nm) is synthesized and characterized. The in vitro uptake and release profiles of cytochrome c by ...the MSN were investigated. The enzymatic activity of the released protein was quantitatively analyzed and compared with that of the native cytochrome c in physiological buffer solutions. We found that the enzymes released from the MSNs are still functional and highly active in catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate) (ABTS) by hydrogen peroxide. In contrast to the fact that cytochrome c is a cell-membrane-impermeable protein, we discovered that the cytochrome c-encapsulated MSNs could be internalized by live human cervical cancer cells (HeLa) and the protein could be released into the cytoplasm. We envision that these MSNs with large pores could serve as a transmembrane delivery vehicle for controlled release of membrane-impermeable proteins in live cells, which may lead to many important biotechnological applications including therapeutics and metabolic manipulation of cells.
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 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)guanidinopropyl (GEGP), and N-folate-3-aminopropyl (FAP). In contrast to the zeta-potential of -18.4 mV for FITC-MSN, the values of zeta-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.
A structurally ordered, CMK-1 type mesoporous carbon nanoparticle (MCN) material was successfully synthesized by using a MCM-48 type mesoporous silica nanoparticle as template. The structure of MCN ...was analyzed by a series of different techniques, including the scanning and transmission electron microscopy, powder X-ray diffraction, and N2 sorption analysis. To the best of our knowledge, no study has been reported prior to our investigation on the utilization of these structurally ordered mesoporous carbon nanoparticles for the delivery of membrane impermeable chemical agents inside of eukaryotic cells. The cellular uptake efficiency and biocompatibility of MCN with human cervical cancer cells (HeLa) were investigated. Our results show that the inhibitory concentration (IC50) value of MCN is very high (>50 microg/mL per million cells) indicating that MCN is fairly biocompatible in vitro. Also, a membrane impermeable fluorescence dye, Fura-2, was loaded to the mesoporous matrix of MCN. We demonstrated that the MCN material could indeed serve as a transmembrane carrier for delivering Fura-2 through the cell membrane to release these molecules inside of live HeLa cells. We envision that further developments of this MCN material will lead to a new generation of nanodevices for transmembrane delivery and intracellular release applications.
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