Nanocomposite based on Gd2O3 nanoparticles and drug 5-fluorouracil as potential theranostic nano-cargo system.

We have prepared silica matrix with hexagonal symmetry of pores (SBA-15) and loaded it with anticancer drug 5-Fluorouracil (5-FU) to promote it as a drug delivery system. Gd2O3 nanoparticles were incorporated into the matrix to enhance nanosystems applicability as contrast agent for MRI, thus enabled this nanocomposite to be used as multifunctional nano-based therapeutic agent. Drug release profile was obtained by UV-VIS spectroscopy, and it indicates the prolongated release of 5-FU during the first hours and the total release after 5 h. The cytotoxicity tests using MTT-assay, fluorescent microscopy, bright-field microscopy, and flow cytometry were carried out using human glioma U87 MG cells and SK BR 3 cells. The nanocomposite with anticancer drug (Gd2O3/SBA-15/5FU) showed toxic behaviour towards studied cells, unlike nanocomposite without drug (Gd2O3/SBA-15) that was non-toxic. Our drug delivery system was designed to minimalize negative effect of Gd3+ ions at magnetic resonance imaging and drug 5-FU on healthy cells due to their encapsulation into biocompatible silica matrix, so the Gd3+ ions are more stable (in comparison to chelates), lower therapeutic dose of 5-FU is needed and its prolongated release from silica pores was confirmed. Very good T1 contrast in MR images was observed even at low concentrations, thus this nanosystem can be potentially used as contrast imaging agent.

In vivo study of light-driven naproxen release from gated mesoporous silica drug delivery system.

A drug delivery system based on mesoporous particles MCM-41 was post-synthetically modified by photo-sensitive ligand, methyl-(2E)-3-(4-(triethoxysilyl)-propoxyphenyl)-2-propenoate (CA) and the pores of MCM-41 particles were loaded with Naproxen sodium salt (NAP). The CA was used as a photoactive molecule that can undergo a reversible photo-dimerization by [2π + 2π] cycloaddition when irradiated with UV light of specific wavelengths. Thus, it has a function of gate-keeper that is responsible for opening/closing the pores and minimizing premature release of NAP. The physicochemical properties of the prepared system were studied by infrared spectroscopy (IR), nitrogen adsorption measurements, thermogravimetric analysis (TGA), scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDX). The mechanism of the opening/closing pores was confirmed by UV measurements. In vitro and in vivo drug release experiments and the concentration of released NAP was determined by UV spectroscopy and high-performance liquid chromatography (HPLC). In vivo drug release in the blood circulatory system of rats has demonstrated the effective photo-cleavage reaction of CA molecules after UV-light stimulation. The localization and morphological changes of the particles were studied in the blood and liver of rats at different time intervals. The particles in the blood have been shown to retain their original rod-like shape, and the particles in the liver have been hydrolysed, which has resulted in spherical shape with a reduced size.

Novel Lanthanide(III) Porphyrin-Based Metal-Organic Frameworks: Structure, Gas Adsorption, and Magnetic Properties.

The present work focuses on the hydrothermal synthesis and properties of porous coordination polymers of metal-porphyrin framework (MPF) type, namely, {[Pr4(H2TPPS)3]·11H2O} n (UPJS-10), {[Eu/Sm(H2TPPS)]·H3O+·16H2O} n (UPJS-11), and {[Ce4(H2TPPS)3]·11H2O} n (UPJS-12) (H2TPPS = 4,4',4″,4‴-(porphyrin-5,10,15,20-tetrayl)tetrakisbenzenesulfonate(4-)). The compounds were characterized using several analytical techniques: infrared spectroscopy, thermogravimetric measurements, elemental analysis, gas adsorption measurements, and single-crystal structure analysis (SXRD). The results of SXRD revealed a three-dimensional open porous framework containing crossing cavities propagating along all crystallographic axes. Coordination of H2TPPS4- ligands with Ln(III) ions leads to the formation of 1D polymeric chains propagating along the c crystallographic axis. Argon sorption measurements at -186 °C show that the activated MPFs have apparent BET surface areas of 260 m2 g-1 (UPJS-10) and 230 m2 g-1 (UPJS-12). Carbon dioxide adsorption isotherms at 0 °C show adsorption capacities up to 1 bar of 9.8 wt % for UPJS-10 and 8.6 wt % for UPJS-12. At a temperature of 20 °C, the respective CO2 adsorption capacities decreased to 6.95 and 5.99 wt %, respectively. The magnetic properties of UPJS-10 are characterized by the presence of a close-lying nonmagnetic ground singlet and excited doublet states in the electronic spectrum of Pr(III) ions. A much larger energy difference was suggested between the two lowest Kramers doublets of Ce(III) ions in UPJS-12. Finally, the analysis of X-band EPR spectra revealed the presence of radical spins, which were tentatively assigned to be originating from the porphyrin ligands.

Magnetic Characterization and Moderate Cytotoxicity of Magnetic Mesoporous Silica Nanocomposite for Drug Delivery of Naproxen.

In this study, we describe the magnetic and structural properties and cytotoxicity of drug delivery composite (DDC) consisting of hexagonally ordered mesoporous silica, iron oxide magnetic nanoparticles (Fe2O3), and the drug naproxen (Napro). The nonsteroidal anti-inflammatory drug (NSAID) naproxen was adsorbed into the pores of MCM-41 silica after the ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) encapsulation. Our results confirm the suppression of the Brownian relaxation process caused by a "gripping effect" since the rotation of the whole particle encapsulated in the porous system of mesoporous silica was disabled. This behavior was observed for the first time, to the best of our knowledge. Therefore, the dominant relaxation mechanism in powder and liquid form is the Néel process when the rotation of the nanoparticle's magnetic moment is responsible for the relaxation. The in vitro cytotoxicity tests were performed using human glioma U87 MG cells, and the moderate manifestation of cell death, although at high concentrations of studied systems, was observed with fluorescent labeling by AnnexinV/FITC. All our results indicate that the as-prepared MCM-41/Napro/Fe2O3 composite has a potential application as a drug nanocarrier for magnetic-targeted drug delivery.

Mesoporous Silica as a Drug Delivery System for Naproxen: Influence of Surface Functionalization.

In this work we describe the relationship between surface modification of hexagonally ordered mesoporous silica SBA-15 and loading/release characteristics of nonsteroidal anti-inflammatory drug (NSAID) naproxen. Mesoporous silica (MPS) was modified with 3-aminopropyl, phenyl and cyclohexyl groups by grafting method. Naproxen was adsorbed into pores of the prepared MPS from ethanol solution using a solvent evaporation method. The release of the drug was performed in buffer medium at pH 2 and physiological solution at pH 7.4. Parent MPSs as well as naproxen loaded MPSs were characterized using physicochemical techniques such as nitrogen adsorption/desorption, thermogravimetric analysis (TG), Zeta potential analysis, Fourier transform infrared spectroscopy (FT-IR), and elemental analysis. The amount of naproxen released from the MPSs into the medium was determined by high-performance liquid chromatography (HPLC). It was shown that the adsorption and desorption characteristics of naproxen are dependent on the pH of the solution and the surface functionalization of the host.

Doxorobicin as cargo in a redox-responsive drug delivery system capped with water dispersible ZnS nanoparticles.

In this work, we have prepared and investigated a redox-responsive drug delivery system (DDS) based on a porous carrier. Doxorubicin (DOX), a chemotherapy medication for treatment of different kinds of cancer, was used as a model drug in the study. DOX was loaded in ordered hexagonal mesoporous silica SBA-15, a nanoporous material with good biocompatibility, stability, large pore size and specific surface area (S BET = 908 m2 g-1, V P = 0.79 cm3 g-1, d = 5.9 nm) and easy surface modification. To prepare the redox-responsive system, cystamine derivative ligands, with redox active disulphide linkers were grafted onto the surface of SBA-15. To ensure no significant premature release of DOX from the porous system, thioglycolic acid modified ZnS nanoparticles (ZnS-COOH NPs) were used as pore capping agents. The grafted redox-responsive cystamine derivative ligand containing disulphide linkers was bonded by a peptide bond to the thioglycolic acid groups of ZnS-COOH NPs, capping the pores. Once the disulphide bond was cleaved, the ZnS-COOH NPs caps were released and pores were opened to deliver the DOX cargo. The dithiol bond was cleavable by redox active molecules such as dithiothreitol (DTT) or glutathione, the concentration of which in cancer cells is 4 times higher than in healthy cells. The redox release of DOX was studied in two different media, physiological saline solution with DTT and saline without DTT. The prepared DDS proved the concept of redox responsive release. All samples were characterised by powder X-ray diffraction (XRD), transition electron microscopy (TEM), nitrogen adsorption/desorption at 77 K, Fourier-transform infrared spectroscopy (FTIR), thermal analysis and zeta potential measurements. The presence of semiconducting ZnS nanoparticle caps on the pore openings was detected by magnetic measurements using SQUID magnetometry showing that such cargo systems could be monitored using magnetic measurements which opens up the possibilities of using such drug delivery systems as theranostic agents.

Size and distribution of the iron oxide nanoparticles in SBA-15 nanoporous silica via SANS study.

Structural characteristics of nanocomposite series consisting of iron oxide nanoparticles (NPs) embedded in the regular pores of amorphous silica matrix (SBA-15) were investigated by means of small angle neutron scattering (SANS). By virtue of unique neutron properties, insight into the inner structure and matter organization of this kind of systems was facilitated for the first time. Based on rigorous experimental support, fundamental model describing the neutron scattering intensity distribution was proposed by assuming general composite structural features. Model application to SANS data confirmed the presence of iron oxide NPs in the body of examined matrices, providing additional information on their shape, concentration and size distribution. Scattering superposition principle employed in the model conception allows for tailoring its fundamental characteristics, and renders it a potent and versatile tool for a wide range of applications.

Large and tunable magnetocaloric effect in gadolinium-organic framework: tuning by solvent exchange.

Magnetic properties of three variants of MOF-76(Gd), {[Gd(BTC)(H2O)]·G}n (BTC = benzene-1,3,5-tricarboxylate, G = guest molecules) were investigated by static susceptibility, isothermal magnetization and specific heat capacity measurements. In the study we used as synthesized MOF-76(Gd)-DMF (1) (G = DMF = dimethylformamide), containing DMF molecules in the cavity system, compound MOF-76(Gd) (2), activated complex without solvents in the cavities and water exchanged sample MOF-76(Gd)-H2O (3). A pronounced change in the magnetic entropy was found near the critical temperature for all three compounds. It was shown, that magnetic entropy change depends on the solvatation of the MOF. The highest value entropy change, ΔSMpk(T) was observed for compound 2 (ΔSMpk(T) = 42 J kg-1 K-1 at 1.8 K for ΔH = 5 T). The ΔSMpk(T) for the compounds 1, 2 and 3 reached 81.8, 88.4 and 100% of the theoretical values, respectively. This suggests that in compound 3 Gd3+···Gd3+ antiferromagnetic interactions are decoupled gradually, and higher fields promote a larger decoupling between the individual spin centers. The observed entropy changes of compounds were comparable with other magnetic refrigerants proposed for low-temperature applications. To study the magnetothermal effect of 2 (the sample with largest -ΔSMpk), the temperature-dependent heat capacities (C) at different fields were measured. The value of magnetic entropy S obtained from heat capacities (39.5 J kg-1 K-1 at 1.8 K for an applied magnetic field change of 5 T) was in good agreement with that derived from the magnetization data (42 J kg-1 K-1 at 1.8 K).

A drug delivery system based on switchable photo-controlled p-coumaric acid derivatives anchored on mesoporous silica.

A stimuli-responsive drug delivery system consisting of mesoporous silica with its surface modified by p-coumaric acid derivatives (CA) as photo-switchable ligands was studied for the delivery of the non-steroidal anti-inflammatory drug (NSAID) naproxen. For this purpose, MCM-41 mesoporous silica material was prepared and post-synthetically modified by the grafting of a triethoxysilyl derivative of p-coumaric acid, which undergoes a reversible photo-dimerization under UV irradiation and creates the "valves" on the surface of silica allowing targeted opening/closing of the pores. Naproxen was encapsulated into grafted MCM-41 and drug release studies were performed in two different media, in a simulated gastric fluid (pH = 2) and in a simulated body fluid (pH = 7.4). Differences in drug release were observed after irradiation of the material using UV light at λ = 365 nm (closed pore configuration) and UV light at λ = 254 nm (opened pore configuration).