Concept: Mesoporous silica
Drug molecules with lack of specificity and solubility lead patients to take high doses of the drug to achieve sufficient therapeutic effects. This is a leading cause of adverse drug reactions, particularly for drugs with narrow therapeutic window or cytotoxic chemotherapeutics. To address these problems, there are various functional biocompatible drug carriers available in the market, which can deliver therapeutic agents to the target site in a controlled manner. Among the carriers developed thus far, mesoporous materials emerged as a promising candidate that can deliver a variety of drug molecules in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles are widely used as a delivery reagent because silica possesses favourable chemical properties, thermal stability and biocompatibility. Currently, sol-gel-derived mesoporous silica nanoparticles in soft conditions are of main interest due to simplicity in production and modification and the capacity to maintain function of bioactive agents. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release. The properties of mesopores, including pore size and porosity as well as the surface properties, can be altered depending on additives used to fabricate mesoporous silica nanoparticles. Active surface enables functionalisation to modify surface properties and link therapeutic molecules. The tuneable mesopore structure and modifiable surface of mesoporous silica nanoparticle allow incorporation of various classes of drug molecules and controlled delivery to the target sites. This review aims to present the state of knowledge of currently available drug delivery system and identify properties of an ideal drug carrier for specific application, focusing on mesoporous silica nanoparticles.
The ability of nanoparticles to target tumors and to enable site-specific drug release provides a unique system for the delivery of effective therapy with reduced toxic side effects. In this study, we used mesoporous silica nanoparticles (MSN) to fabricate a targeted drug delivery system that is responsive to hyaluronidase (HAase). Following engraftment of desthiobiotin onto the surface of MSN, a streptavidin complex was generated which was functionalized with biotin-modified hyaluronic acid (HA) to enable controlled drug release at cancer cells expressing HAase. Various technologies were used to confirm the successful fabrication of this MSN-based nanocarrier system for targeted drug delivery. In vitro analyses showed that the release of doxorubicin hydrochloride (Dox) was accelerated significantly in the presence of biotin or HAase and accelerated further in the presence of biotin and HAase. Uptake by cancer cells was mediated efficiently by CD44-receptor mediated endocytosis and that the MSN exhibited good biocompatibility in vitro and in vivo. MSN-HA/Dox nanoparticles induced apoptosis in cancer cells more efficiently than free Dox and inhibited tumor growth with minimal systemic toxicity in vivo. Collectively, our findings offered a preclinical proof of concept for a novel targeted drug delivery carrier system for cancer therapy.
- Integrative biology : quantitative biosciences from nano to macro
- Published over 6 years ago
Efficient and safe drug delivery has always been a challenge in medicine. The use of nanotechnology, such as the development of nano drug delivery systems (DDS), has received great attention with high enthusiasm owing to the potential that nanocarriers can theoretically act as “magic bullets” and selectively target affected organs and cells while sparing normal tissues. The family of nano DDS includes conventional nano drug delivery materials such as lipids and polymers that have been scaled to the nanometer size range. With the rapid development of synthesis and characterization techniques for engineered nanomaterials, new DDS platforms have emerged, including inorganic based nanocarriers, such as mesoporous silica nanoparticles (MSNP). MSNP are able to act as a multifunctional delivery platform that is capable of delivering therapeutic elements to a variety of disease models (especially cancer) at cellular and in vivo levels. Furthermore, MSNP have shown to be exceptional delivery platforms capable of protectively packaging hydrophobic and hydrophilic drug molecules as well as other therapeutic elements for controlled on-demand delivery. In addition, MSNP have demonstrated the capability to image the delivery site for theranostic purposes. These functionalities have led to the development of MSNP as novel multifunctional nanocarriers, and therefore provide them with unique advantages compared to other nanocarriers.
This pHLIP is no flop: Functionalizing mesoporous silica nanoparticles (MSNs) with pHLIPss peptide provides a controlled-release nanoparticle drug delivery system targeting the acidic tumor microenvironment. At low pH values, pHLIPss inserts into the cell membrane and translocates carriers into cells, where the cargo is released by the cleavage of the pHLIPss disulfide bonds.
A facile vacuum-assisted vapor deposition process has been developed to control the pore size of ordered mesoporous silica materials in a stepwise manner with angstrom precision, providing an unprecedented paradigm to screen a designer hydrophobic drug nano-carrier with optimized pore diameter to maximize drug solubility.
A new technique that allows direct three-dimensional (3D) investigations of mesopores in carbon materials and quantitative characterization of their physical properties is reported. Focused ion beam nanotomography (FIB-nt) is performed by a serial sectioning procedure with a dual beam FIB-scanning electron microscopy instrument. Mesoporous carbons (MPCs) with tailored mesopore size are produced by carbonization of resorcinol-formaldehyde gels in the presence of a cationic surfactant as a pore stabilizer. A visual 3D morphology representation of disordered porous carbon is shown. Pore size distribution of MPCs is determined by the FIB-nt technique and nitrogen sorption isotherm methods to compare both results. The obtained MPCs exhibit pore sizes of 4.7, 7.2, and 18.3 nm, and a specific surface area of ca. 560 m2/g.
A novel pH-responsive nano-carrier MSNs-PAA, possessing mesoporous silica nanoparticles (MSNs) cores and poly(acrylic acid) (PAA) shell-layers, was developed for controlled release of salidroside. The vinyl double bonds modified MSNs were synthesized by using cetyltrimethylammonium bromide (CTAB) as templates, tetraethyl orthosilicate (TEOS) as silicon source, and 3-(trimethoxylsilyl) propyl methacrylate (MPS) as surface modification functionalities. The pH-responsive layers of PAA were grafted onto the vinyl double bonds of the MSNs via precipitation polymerization, producing the MSNs-PAA with a hollow cubic core and mesoporous shell with penetrating pore channels. The characteristic results also showed that PAA was successfully grafted onto the surface of the MSNs. The MSNs-PAA was investigated as carriers for loading and regulating the release of salidroside in different pH solutions for the first time. The results demonstrated that the PAA layers on the surface of MSNs-PAA exhibited opened and closed states at different pH values, and thus could regulate the uptake and release of salidroside. The application of such pH-responsive nano-carrier might offer a potential platform for controlled delivery and increasing the bioavailability of drugs.
Considerable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growth trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.Probing the growth pathways of quasicrystalline materials, where tiling units arrange with local but no long-range order, remains challenging. Here, the authors demonstrate that dodecagonal tiling of mesoporous silica nanoparticles occurs via irreversible packing of micelles with non-uniform size distribution.
Near-infrared (NIR) light is an attractive stimulus due to its noninvasive and deep tissue penetration. Particularly, NIR light is utilized for cancer thermotherapy and on-demand release of drugs by the disruption of the delivery carriers. Here we have prepared a novel NIR-responsive DNA-hybrid-gated nanocarrier based on the mesoporous silica coated Cu1.8S nanoparticles. The Cu1.8S nanoparticles, possessing high photothermal conversion efficiency under 980 nm laser, were chosen as photothermal agents. Mesoporous silica structure could be used for drug storage/delivery and modified with aptamer-modified GC-rich DNA-helix as gatekeepers, drug vectors, and targeting ligand. Simultaneously, the as-produced photothermal effect can cause denaturation of DNA double strands, which triggered the drug release of DNA-helix-loaded doxorubicin and mesopore-loaded curcumin, resulting in a synergistic therapeutic effect. The Cu1.8S@mSiO2 nanocomposites endocytosed by cancer cells through aptamer-mediated mode are able to generate rational release of doxorubicin/curcumin under NIR irradiation, strongly enhancing synergistic the growth-inhibitory effect of curcumin against doxorubicin in MCF-7 cells, which was associated with a strong mitochondrial-mediated cell apoptosis progression. The underlying mechanism of apoptosis showed a strong inhibitory effect of combination on Bcl-2, Bcl-xL, Mcl-1 protein expression and caspase 3/9 activity, upregulated the expression level of Bak and Bax. Therefore, the Cu1.8S@mSiO2 with efficient synergistic therapeutic efficiency is a potential multifunctional cancer therapy nanoplatform.
In this review, we summarize the latest developments and give a perspective on future applications of mesoporous silica nanoparticles (MSNs) in regenerative medicine. MSNs constitute a flexible platform for controlled delivery of drugs and imaging agents in tissue engineering and stem cell therapy. We highlight the recent advances in applying MSNs for controlled drug delivery and stem cell tracking. We touch upon novel functions of MSNs in real time imaging of drug release and biological function, and as tools to control the chemical and mechanical environment of stem cells. We discuss the need for novel model systems for studying biofunctionality and biocompatibility of MSNs, and how the interdisciplinary activities within the field will advance biotechnology research.