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.

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.

Mimicking red blood cell lipid membrane to enhance the hemocompatibility of large-pore mesoporous silica.

Mesoporous silica nanoparticles (MSNs) have been repeatedly demonstrated as potential drug-delivery devices. The study of biocompatibility and interaction of these materials with the various cell types is of great interest with regard to the development of viable pharmaceutical products. By mimicking the cholesterol, phosphatidylcholine, and phosphatidylethanolamine composition of the outer leaflet of a human red blood cell (RBC), lipid-bilayer-coated mesoporous silica particles show considerably improved hemocompatibility over phosphatidylcholine-coated and uncoated large-pore MSN (l-MSN). These inorganic/organic composite nanomaterials are shown to be capable of interfacing with RBCs without damaging the cells even at relatively high concentrations, as observed through electron microscopy, UV-vis spectroscopy, and flow cytometry analyses. Interestingly, the absence of cholesterol in the outer bilayer composition is shown to produce toxic effects without resulting in hemolysis. By maintaining the ζ potential of lipid-bilayer-functionalized MSNs similar to that of the hemolytic l-MSNs, we demonstrate that the bilayer composition, and not the surface charge, plays a significant role in determining the hemocompatibility of MSN-based materials.

Polymer-based stimuli-responsive nanosystems for biomedical applications.

The application of organic polymers and inorganic/organic hybrid systems in numerous fields of biotechnology has seen a considerable growth in recent years. Typically, organic polymers with diverse structures, compositional variations and differing molecular weights have been utilized to assemble polymeric nanosystems such as polymeric micelles, polymersomes, and nanohydrogels with unique features and structural properties. The architecture of these polymeric nanosystems involves the use of both hydrophobic and hydrophilic polymeric blocks, making them suitable as vehicles for diagnostic and therapeutic applications. Recently, "smart" or "intelligent" polymers have attracted significant attention in the biomedical field wherein careful introduction of specific polymeric modalities changes a banal polymeric nanosystem to an advanced stimuli-responsive nanosystem capable of performing extraordinary functions in response to an internal or external trigger such as pH, temperature, redox, enzymes, light, magnetic, or ultrasound. Further, incorporation of inorganic nanoparticles such as gold, silica, or iron oxide with surface-bound stimuli-responsive polymers offers additional advantages and multifunctionality in the field of nanomedicine. This review covers the physical properties and applications of both organic and organic/inorganic hybrid nanosystems with specific recent breakthroughs in drug delivery, imaging, tissue engineering, and separations and provides a brief discussion on the future direction.

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.

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.