Functionalization of mesoporous silica nanoparticles for targeting, biocompatibility, combined cancer therapies and theragnosis.

The advent of Nanotechnology has paved a way for improved disease treatment strategies, the most noteworthy being the mesoporous silica nanoparticles (MSNs) which have gained much recent attention in the field of cancer therapy and its diagnosis. The flaws of the current-day strategies can be overcome by this superior technology through its targeting ability in delivering drugs and image able agents specifically to the tumor sites. MSNs have unique biocompatibility features, its high surface area which contributes in large amount of drug loading and its facility to monitor size and shape of the nanoparticles are few of the positives which makes this technology an enormous asset for the field of Nanotechnology. This review paper is structured in such a way wherein we initially have discussed about the synthesis methods and various functionalization approaches for MSN followed by the different methods used for targeting cancer cells and the latest advances in controlled drug release. Some of the highlights of this review are the biocompatibility of MSNs, in vivo results of MSNs on cancer therapy. This review paper also shortly discuss about combined cancer therapies to overcome the challenges in current-day cancer treatment. Finally, we converge briefly on the recent advancements in the use of hybrid MSNs for obtaining multiple functions.

Surface-functionalized layered double hydroxide nanocontainers as bile acid sequestrants for lowering hyperlipidemia.

The surface modification of two-dimensional (2D) nanocontainers with versatile chemical functionalities offers enormous advantages in medicine owing to their altered physicochemical properties. In this study, we demonstrate the fabrication of surface-functionalized layered double hydroxides (LDHs) towards their use as effective intestinal bile acid sequestrants. To demonstrate these aspects, the LDHs are initially modified with an amino silane, N1-(3-trimethoxysilylpropyl) diethylenetriamine (LDHs-N3),which, on the one hand, subsequently used for the fabrication of the dendrimer by repetitive immobilization of ethylene diamine using methyl acrylate as a spacer. On the other hand, these surface-functionalized LDHs are wrapped with an anionic enteric co-polymer to not only prevent the degradation but also increase the stability of these 2D nanoplates in an acidic environment of the stomach to explore the in vivo efficacy. In vitro cholic acid adsorption results showed that these surface-functionalized LDHs displayed tremendous adsorption ability of bile salt. Consequently, the bile salt adsorption results in vivo in mice confirmed that the enteric polymer-coated diethylenetriamine silane-modified LDHs, resulting in the reduced cholesterol by 8.2% in the high fat diet-fed mice compared to that of the oil treatment group with augmented 28% of cholesterol, which gained weight by 6.7% in 4 weeks. Notably, the relative organ (liver and kidney) weight analysis and the tissue section of histology results indicated that the modified LDHs showed high biocompatibility in vivo. Together, our findings validate that these surface-functionalized 2D nanoplates have great potential as effective intestinal bile acid sequestrants.

A focal adhesion kinase inhibitor 16-hydroxy-cleroda-3,13-dien-16,15-olide incorporated into enteric-coated nanoparticles for controlled anti-glioma drug delivery.

16-Hydroxy-cleroda-3,13-dien-16,15-olide (HCD) which is extracted from a medicinal plant, Polyalthia longifolia, was shown to exhibit anticancer activity through apoptosis and FAK inhibition in our previous study. To improve its solubility and efficacy, a novel HCD delivery system using copper-substituted mesoporous silica nanoparticles (MSNs) was designed as a delivery vehicle, and the outer surfaces of MSNs were further coated with enteric polymers to prevent the drug from leaching in the stomach acid. All the data regarding synthesis and physical characterization, including Zeta potential, FT-IR spectra, N2 adsorption-desorption isotherms (BET), drug loading, powder X-ray diffraction, Thermo gravimetric analysis (TGA), Transmission electron microscopy (TEM), and Scanning electron microscopy (SEM) were well characterized. The non-coated MSN-HCD exposed to acidic pH (1.2) showed a rapid degradation of the drug, whereas the enteric-coated samples presented a sustained release profile in the gastrointestinal pHs. Cell cytotoxicity was further confirmed by the MTT-C6 Glioma cell line, in vitro. When compared with the control and pure HCD, the MSN-HCD revealed a potential anti-proliferation effect via the synergistic effect of the drug and the MSN vehicle. Additionally, this MSN-HCD had the effect of increasing the reactive oxygen species (ROS) levels and altered the Mitochondria membrane potential (MMP) in C6 cell line. The in vivo anti-tumor efficacy of enteric-coated MSN-HCD was evaluated by C6 Glioma bearing xenograft nude mice, and enteric-coated MSN-HCD clearly exhibited the greatest anti-glioma activity, as compared to the pure HCD and the untreated control. In terms of the effective treatment of brain glioma, this study provides conclusive evidence of the successful development of the anti-cancer agent HCD conjugated with enteric-coated MSN as a delivery control mechanism with enhanced dissolution characteristics.

Multi-laminated metal hydroxide nanocontainers for oral-specific delivery for bioavailability improvement and treatment of inflammatory paw edema in mice.

Multiple layers of pH-sensitive enteric copolymers were coated over layered double hydroxide (LDH) nanoparticles for controllable drug release and improved solubility of hydrophobic drugs. The nano-sized LDH carriers significantly improved the accessibility of sulfasalazine molecules that have positively charged frameworks. In addition, the successful encapsulation of negatively charged enteric copolymers was achieved via electrostatic attractions. The multi-layered enteric polymer coating could potentially protect nanoparticle dissolution at gastric pH and accelerate the dissolution velocity, which would improve the drug bioavailability in the colon. Next, biological studies of this formulation indicated a highly protective effect from the scavenging of superoxide free radicals and diethyl maleate (DEM) induced lipid peroxidation, which are major cell signalling pathways for inflammation. The histological view of the liver and kidney sections revealed that the nanoformulation is safe and highly biocompatible. The animal studies conducted via paw inflammation induced by complete Freund's adjuvant (CFA) revealed that enteric-coated LDH-sulfasalazine nanoparticles provided a sustained release that maintained the sulfasalazine concentrations in a therapeutic window. Therefore, this nanoformulation exhibited preferential efficacy in reducing the CFA-induced inflammation especially at day 4.