Silica Nanoparticles For Biomedical Applications Research Articles

Simultaneous Microfluidic Synthesis of Multi-Sized Silica Nanoparticles for Biomedical Applications

Simultaneous Microfluidic Synthesis of Multi-Sized Silica Nanoparticles for Biomedical Applications

Engineering mesoporous silica nanoparticles for drug delivery: where are we after two decades?

The present review details a chronological description of the events that took place during the development of mesoporous materials, their different synthetic routes and their use as drug delivery systems. The outstanding textural properties of these materials quickly inspired their translation to the nanoscale dimension leading to mesoporous silica nanoparticles (MSNs). The different aspects of introducing pharmaceutical agents into the pores of these nanocarriers, together with their possible biodistribution and clearance routes, would be described here. The development of smart nanocarriers that are able to release a high local concentration of the therapeutic cargo on-demand after the application of certain stimuli would be reviewed here, together with their ability to deliver the therapeutic cargo to precise locations in the body. The huge progress in the design and development of MSNs for biomedical applications, including the potential treatment of different diseases, during the last 20 years will be collated here, together with the required work that still needs to be done to achieve the clinical translation of these materials. This review was conceived to stand out from past reports since it aims to tell the story of the development of mesoporous materials and their use as drug delivery systems by some of the story makers, who could be considered to be among the pioneers in this area.

Defect Engineering of Mesoporous Silica Nanoparticles for Biomedical Applications

ConspectusThe goddess Venus has been known for her armless beauty. Such a unique artistic effect teaches us that the imperfection in one aspect may result in a great aesthetics in another aspect. The existence of structural defects in nanomaterials (substitutional impurities and vacancies) endows them with diverse and fascinating physicochemical properties, such as optical properties and redox reaction capabilities. Therefore, defect engineering of controllably regulating the types and concentrations of defects in nanoparticles has been paid great attention in nanosynthetic chemistry for tailoring the performances of nanomaterials for diversified practical applications, such as biomedical applications.Mesoporous silica nanoparticles (MSNs) have been extensively applied as nanocarriers in biomedicine, due to their well-defined pore structure and particle morphology, extraordinarily large specific surface area and pore volume, tunable pore size, and framework composition. These nanoparticles have been considered as promising candidates for application in multiple therapeutic or diagnostic applications, by acting as drug carriers or supports for functional materials. The synthesis of MSN is usually based on sol–gel chemistry according to a bottom-up approach in a hydrothermal environment, where the silica precursor tetraethoxysilane molecules condense with each other and −Si–O–Si– bonds form consequently, under the assistance of surfactants as structural-directing agents, finally resulting in the formation of a mesoporous nanostructure. Accompanying the pore structure evolution, which has been being the major focus in the MSNs synthesis and application in the past decades, alternatively, the composition of MSN framework can also be elaborately engineered for the material functionalization and the application broadenings of MSNs, facilely by properly regulating the experimental conditions and reactants. Especially, the defect engineering of MSNs has been extensively explored very recently for broadening biomedical applications of these nanocarriers.In the last several years, our laboratory has developed three general strategies to engineer various functional chemical constituents in the MSN framework as structural defects, conferring the nanocarriers with multiple additional functions: (1) doping metal element M (M = Fe, Cu, Mn, Mg, Ca) in silica to form a −Si–O–M– metal silicate hybrid framework; (2) hybridizing organic group R (R = thioether, ethane, phenylene) in silica to fabricate a −Si–R–Si– molecularly organic–inorganic hybrid framework; (3) creating oxygen vacancies in silica by forming an oxygen-deficient framework abundant with −Si–Si– bonds. These material-engineering approaches have led to the generation of numbers of structural defects in the pristine silsesquioxane framework of MSNs, making these “defective nanoparticles” capable of presenting various unique physicochemical properties benefiting biomedical applications, such as triggered biodegradability for controlled drug release; catalytic performance for triggering in vivo chemical reactions generating therapeutic effects; paramagnetism for enabling magnetic resonance imaging; luminescent property for cell imaging, etc. In this Account, we will provide a concise and concentrated summary on the advances in the preparation of defective MSNs mainly in our laboratory, as well as the therapeutic and diagnostic applications of these versatile nanosystems, hoping to provide more inspirations to future nanomedicine design.

Well-defined polyester-grafted silica nanoparticles for biomedical applications: Synthesis and quantitative characterization

Polyester-based composites with silica nanoparticles fillers are promising candidates as biomaterials due to improved mechanical and biological properties. However, nanofillers use generally leads to an inhomogeneous distribution inside the polymer matrix because of agglomeration, decreasing composites overall performances. In view of improving nanofillers dispersion, we developed a synthesis and characterization method to design poly(d,l-lactide)-grafted silica nanoparticles using “grafting to” method and to quantify the amount of grafted poly(d,l-lactide). Firstly, well-defined N-hydroxysuccinimide ester poly(d,l-lactide)s were synthesized through a new pathway. Then, amino-functionalized silica nanoparticles were grafted with those customized polyesters yielding an amide covalent bond between both reagents. Such PDLLA-grafted nanoparticles were precisely characterized and the grafting amount was quantified using a dual approach based on TGA and FTIR analysis. The synthesis and the characterization methods developed constitute a robust and reproducible way to design well-defined polymer-grafted silica nanoparticles that could be used as nanofillers in polymer matrix nanocomposites for biomedical applications.

Biomedical application of mesoporous silica nanoparticles as delivery systems: a biological safety perspective.

The application of mesoporous silica nanoparticles (MSNs) as drug delivery systems to deliver drugs, proteins, and genes has expanded considerably in recent years, using in vitro and animal studies. For future translation to clinical applications, the biological safety aspects of MSNs must be considered carefully. This paper reviews the biosafety of MSNs, examining key issues such as biocompatibility, effects on immune cells and erythrocytes, biodistribution, biodegradation and clearance, and how these vary depending on the effects of the physical and chemical properties of MSNs such as particle size, porosity, morphology, surface charge, and chemical modifications. The future use of MSNs as a delivery system must extend beyond what has been learnt thus far using rodent animal models to encompass larger animals.

Fabrication and characterization of bioactive chitosan microspheres incorporated with mesoporous silica nanoparticles for biomedical applications

Mesoporous silica nanoparticles (MSNs) were prepared using sol–gel method. Chitosan-MSNs microspheres scaffold loaded with ciprofloxacin also prepared via an ionotropic gelation method. The prepared samples were characterized using FE-SEM, TEM, FTIR and XRD analysis. The pore volume and mean pore diameter for MSNs was determined by the Brunauer–Emmett–Teller (BET) method. The in vitro drug test was evaluated by using UV–Vis spectrophotometry at λmax of 275 nm. The estimated (measured) MSNs pore volume and pore diameter were 0.9227 cm3/g and 2.6058 nm, respectively. The Chitosan-MSNs loaded with ciprofloxacin show a spherical surface with good and uniform distribution of the MSNs in the microspheres. The in vitro drug release confirms that the MSNs containing beads shows a retarding release (≈ 90% in 9 h) than beads without MSNs (≈ 90% in 2 h). In the light of these findings, the developed delivery system scaffold holds great potential for bone regeneration by control drug release used in activation osteoblast cells.

Ultrasound responsive mesoporous silica nanoparticles for biomedical applications.

Nanotechnology, which has already revolutionised many technological areas, is expected to transform life sciences. In this sense, nanomedicine could address some of the most important limitations of conventional medicine. In general, nanomedicine includes three major objectives: (1) trap and protect a great amount of therapeutic agents; (2) carry them to the specific site of disease avoiding any leakage; and (3) release on-demand high local concentrations of therapeutic agents. This feature article will make special emphasis on mesoporous silica nanoparticles that release their therapeutic cargo in response to ultrasound.

A Toolbox for the Synthesis of Multifunctionalized Mesoporous Silica Nanoparticles for Biomedical Applications.

Mesoporous silica nanoparticles (MSNs) are considered as promising next-generation nanocarriers for health-related applications. However, their effectiveness mostly relies on their efficient and surface-specific functionalization. In this contribution, we explored different strategies for the rational multistep synthesis of functional MCM-48-type MSNs with selectively created active inner and/or external surfaces. Functional groups were first installed using a combination of (delayed) co-condensation and post-grafting procedures. Both amine [(3-aminopropyl)triethoxysilane (APTS)] and thiol [(3-mercaptopropyl)trimethoxysilane (MPTS)] silanes were used, in various addition sequences. Following this, the different platforms were further functionalized with polyethylene glycol and/or with a pro-chelate ligand used as a magnetic resonance imaging contrast agent (diethylenetriaminepentaacetic acid chelates) and/or loaded with quercetin and/or grafted with an organic dye (rhodamine). The efficiency of the multiple grafting strategies and the effects on the MSN carrier properties are presented. Finally, the colloidal stability of the different systems was evaluated in physiological media, and preliminary tests were performed to verify their drug release capability. The use of MPTS appeared beneficial when compared to APTS in delayed co-condensation procedures to preserve both selective distribution of the functional groups, reactive functionality, and pore ordering. Our results provide in-depth insights into the efficient design of (multi)functional MSNs and especially on the crucial role played by the sequence of step-by-step functionalization methods aiming to produce multipurpose and stable bioplatforms.

Luminescent mesoporous silica nanoparticles for biomedical applications: Synthesis and characterization

We report the synthesis and detailed characterization of intrinsically/lable-free luminescent mesoporous silica nanoparticles (L-MSN), which may have useful biomedical applications. These particles were prepared by modified Stober's method followed by calcination. By optimizing the ratio of (3-aminopropyl triethoxysilane) APTS to tetraetthoxysaline (TEOS), particles with size ~ 43 nm and size dispersion ~ 12% were obtained. The luminescence of L-MSN is suggested to be due to the formation of carbonaceous compounds, giving particles yellowish brown color, during the process of calcination at optimum temperatures ~ 400 °C. Interestingly, our studies suggest that these carbonaceous impurities are carbon dots (C-Dots) and fluorescence anisotropy decay measurements indicate C-Dots as integral part of L-MSN. Luminescent properties of L-MSN were found to be stable as a function of pH as well as long time light exposure. Our results suggest that L-MSN may be explored for biomedical imaging as well as drug delivery applications.

Synthesis and Functionalization of Ordered Large‐Pore Mesoporous Silica Nanoparticles for Biomedical Applications

AbstractA dual surfactant synthetic approach was employed for the synthesis of large‐pore mesoporous silica nanoparticles (MSNs). The as‐synthesized mesoporous silica exhibited not only 2D hexagonal mesostructure with an average pore size of about 7 nm but also a spherical nanoparticulate morphology. A delayed co‐condensation synthesis method was further employed to create site‐specific core‐shell bifunctional MSNs. These core‐shell large‐pore MSNs are biocompatible and can be efficiently taken up by cells. They are therefore promising nanocarriers for cellular delivery purposes.

Externally Controlled Nanomachines on Mesoporous Silica Nanoparticles for Biomedical Applications.

Many machines (including nanomachines) consist of a solid support with moving parts that can undergo large amplitude motion to carry out specific tasks. In this Minireview, we will describe nanomachines that are supported on mesoporous silica nanoparticles that are typically 50-100 nanometers in diameter and have an array of open, readily accessible pores with an average width of a few nanometers. For triggering a large amplitude motion of the moving parts, we will focus primarily on external stimuli such as heat or light. As for the specific task the machines are carrying out, this Minireview will focus on the controlled release of pharmaceutically active agents in biomedical applications. We will discuss examples of how nanomachines can be used for remotely controlled cargo release and how existing machines that were originally designed to respond to internal physiological stimuli could be reconfigured to respond to external stimuli instead.

Synthesis and biocompatibility assessment of sugarcane bagasse-derived biogenic silica nanoparticles for biomedical applications.

Sugarcane bagasse is a fibrous material and an excellent bioresource for biogenic silica. Moreover, sugarcane bagasse has low production costs and is a sustainable precursor for the synthesis of biogenic silica nanoparticles (BSNPs). In this study, we synthesized BSNPs using sugarcane bagasse. The acid pretreatment of sugarcane was carried out in an autoclave, which eliminates metal ions and promotes the hydrolysis of organic substances. Residues of the acid pretreatment were incinerated at different temperatures to determine the role of temperature on the formation of BSNPs. The crystalline nature and morphology of the prepared BSNPs were analyzed using X-ray diffraction analysis and transmission electron microscopy. The X-ray diffraction analysis result indicates that the prepared BSNPs have an amorphous nature. Transmission electron microscopy images confirmed that the BSNPs have an irregular shape with a porous morphology. The biocompatibility of BSNPs was studied by assessing their effect on human lung fibroblast cell viability, morphology, mitochondrial function, reactive oxygen species, and gene expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and microscopy studies suggested that BSNPs do not affect cell viability or morphology. BSNPs slightly affect the mitochondrial membrane potential at high doses. In addition, BSNPs decreased the percentage of human lung fibroblast cell in G1 and G2/M phases and increased the S population. These studies revealed that the BSNPs were biocompatible, indicating that they may be applicable for biomedical applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 340-349, 2017.

Biocompatibility assessment of rice husk-derived biogenic silica nanoparticles for biomedical applications.

Synthetic forms of silica have low biocompatibility, whereas biogenic forms have myriad beneficial effects in current toxicological applications. Among the various sources of biogenic silica, rice husk is considered a valuable agricultural biomass material and a cost-effective resource that can provide biogenic silica for biomedical applications. In the present study, highly pure biogenic silica nanoparticles (bSNPs) were successfully harvested from rice husks using acid digestion under pressurized conditions at 120°C followed by a calcination process. The obtained bSNPs were subjected to phase identification analysis using X-ray diffraction, which revealed the amorphous nature of the bSNPs. The morphologies of the bSNPs were observed using transmission electron microscopy (TEM), which revealed spherical particles 10 to 30 nm in diameter. Furthermore, the biocompatibility of the bSNPs with human lung fibroblast cells (hLFCs) was investigated using a viability assay and assessing cellular morphological changes, intracellular ROS generation, mitochondrial transmembrane potential and oxidative stress-related gene expression. Our results revealed that the bSNPs did not have any significant incompatibility in these in vitro cell-based approaches. These preliminary findings suggest that bSNPs are biocompatible, could be the best alternative to synthetic forms of silica and are applicable to food additive and biomedical applications.

In Vitro Degradation Behavior of Silica Nanoparticles Under Physiological Conditions

Understanding the degradability of silica nanoparticles is significant for the rational design of desired nanomaterials for various biomedical applications. However, the effect of the intrinsic properties of silica nanoparticles, such as particle shape, surface chemistry, and porosity, on kinetic degradation process under different extrinsic conditions has still received little attention. Herein, mesoporous silica nanoparticles (MSNs) with different aspect ratios (ARs, 1, 2, and 4), the corresponding PEG-functionalized MSNs, and amorphous Stöber spherical silica nanoparticles were specially designed and their degradation was evaluated in in vitro simulated physiological media. The results show that shape, surface properties and porosity of nanoparticles, as well as the component of simulated physiological media, play important roles in tuning the degradation kinetics and behaviors. Sphere-shaped MSNs have a faster degradation rate than rod-shaped counterparts. Naked MSNs are eroded from particle external surface, while PEGylated MSNs from interior of particles. And spherical MSNs display more extensive degradation than amorphous silica nanoparticles. The presence of fetal bovine serum (FBS) in Dulbecco's Modified Eagle's Medium (DMEM) can accelerate the degradation process. These results can provide useful guidelines for the rational design of silica nanoparticles for biomedical applications.

Room‐temperature preparation and characterization of poly (ethylene glycol)‐coated silica nanoparticles for biomedical applications

Monodisperse, spherical, polyethylene glycol (PEG)-coated silica nanoparticles have been prepared at room temperature and characterized for the purpose of biomedical applications. The particles were synthesized by the hydrolysis of tetramethyl orthosilicate (TMOS) in alcohol media under catalysis by ammonia, and their size can range from about 50-350 nm in diameter. We studied the particle size and size distribution using a scanning electron microscope (SEM) and an asymmetric field-flow fractionation (AFFF) multiangle static light-scattering instrument. The chemical and/or physical binding of PEG to the silica nanoparticles was studied by infrared spectroscopy, and the weight percentage of PEG attached to the particles was quantified. The PEG-coated silica nanoparticles showed enhanced colloidal stability when redispersed into aqueous solutions from the dried state as a result of the steric stabilization function of the PEG polymer grafted on the surface of particles. A nonspecific protein-binding test was also carried out to show that the PEG coating can help reduce the protein adsorption onto the surface of the particles, relating to the biocompatibility of these PEG-coated particles. Also, the inclusion of magnetic nanoparticles into the silica particles was shown as an example of the possible applications of PEG-coated silica particles. These silica nanoparticles, as a matrix for encapsulation of certain reagents, have potential for applications to in vivo diagnosis, analysis, and measurements inside intact biologic systems.