Mesoporous silica nanoparticles for intracellular controlled drug delivery.

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.

Polymer length distributions for catalytic polymerization within mesoporous materials: non-Markovian behavior associated with partial extrusion.

We analyze a model for polymerization at catalytic sites distributed within parallel linear pores of a mesoporous material. Polymerization occurs primarily by reaction of monomers diffusing into the pores with the ends of polymers near the pore openings. Monomers and polymers undergo single-file diffusion within the pores. Model behavior, including the polymer length distribution, is determined by kinetic Monte Carlo simulation of a suitable atomistic-level lattice model. While the polymers remain within the pore, their length distribution during growth can be described qualitatively by a Markovian rate equation treatment. However, once they become partially extruded, the distribution is shown to exhibit non-Markovian scaling behavior. This feature is attributed to the long-tail in the "return-time distribution" for the protruding end of the partially extruded polymer to return to the pore, such return being necessary for further reaction and growth. The detailed form of the scaled length distribution is elucidated by application of continuous-time random walk theory.

Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers.

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.

Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems.

Recent advancements in controlling the surface properties and particle morphology of the structurally defined mesoporous silica materials with high surface area (>700 m(2) g(-1)) and pore volume (>1 cm(3) g(-1)) have significantly enhanced their biocompatibility. Various methods have been developed for the functionalization of both the internal pore and exterior particle surfaces of these silicates with a tunable pore diameter ranging from 2 to 30 nm and a narrow pore size distribution. Herein, we review the recent research progress on the design of functional mesoporous silica materials for stimuli-responsive controlled release delivery of pharmaceutical drugs, genes, and other chemicals. Furthermore, the recent breakthroughs in utilizing these nanoscale porous materials as sensors for selective detections of various neurotransmitters and biological molecules are summarized.

Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects.

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.

Poly(lactic acid)-coated mesoporous silica nanosphere for controlled release of venlafaxine.

Two types of mesoporous silica nanospheres (MSNs) were synthesized for use as controlled-release agents. One was prepared by grafting with 5,6-dihydroxyhexylsilane (DH-MSN) and the other one by further coating with cholic acid-crosslinked poly(lactic acid) (CA-PLA-MSN). We studied the release of the antidepressant venlafaxine from each of the materials in simulated gastric fluid (SGF), in simulated gastric acid solution (SGA), and in simulated intestinal fluid without pancreatin (SIF). The CA-PLA-MSN material was able to significantly delay the release of the drug in intestinal condition compared with gastric acid surrounding due to the fast decomposition rate of PLA in gastric acid. Moreover, it successfully avoided the initial burst to a certain extent in SGF. The enzyme pepsin played a favorable obstruct role in both DH-MSN and CA-PLA-MSN systems to reduce release rate. A model based on Weibull model was built to fit the release results, and based on it, the mechanisms about release processes were brought out tentatively.

Gatekeeping layer effect: a poly(lactic acid)-coated mesoporous silica nanosphere-based fluorescence probe for detection of amino-containing neurotransmitters.

We have synthesized a poly(lactic acid) coated MCM-41-type mesoporous silica nanosphere (PLA-MSN) material can serve as a fluorescence sensor system for detection of amino-containing neurotransmitters in neutral aqueous buffer. Utilizing the PLA layer as a gatekeeper, we investigated the molecular recognition events between several structurally simple neurotransmitters, i.e., dopamine, tyrosine, and glutamic acid and a pore surface-anchored o-phthalic hemithioacetal (OPTA) group, which functions as a fluorescence-sensing group that can react with the neurotransmitters with primary amine groups and form the corresponding fluorescent isoindole products. The poly(lactic acid) layer of the PLA-MSN sensor showed a unique "sieving" effect that regulates the rates of diffusion of the amino acid-based neurotransmitters into the sensor mesopores of the material.

A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent.

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.

A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules.

An MCM-41 type mesoporous silica nanosphere-based (MSN) controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide (CdS) nanocrystals as chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. We studied the stimuli-responsive release profiles of vancomycin- and adenosine triphosphate (ATP)-loaded MSN delivery systems by using disulfide bond-reducing molecules, such as dithiothreitol (DTT) and mercaptoethanol (ME), as release triggers. The biocompatibility and delivery efficiency of the MSN system with neuroglial cells (astrocytes) in vitro were demonstrated. In contrast to many current delivery systems, the molecules of interest were encapsulated inside the porous framework of the MSN not by adsorption or sol-gel types of entrapment but by capping the openings of the mesoporous channels with size-defined CdS nanoparticles to physically block the drugs/neurotransmitters of certain sizes from leaching out. We envision that this new MSN system could play a significant role in developing new generations of site-selective, controlled-release delivery nanodevices.