Cancer is one of the main causes of death around the world, lacking efficient clinical treatments that generally present severe side effects. In recent years, various nanosystems have been explored ...to specifically target tumor tissues, enhancing the efficacy of cancer treatment and minimizing the side effects. In particular, bladder cancer is the ninth most common cancer worldwide and presents a high survival rate but serious recurrence levels, demanding an improvement in the existent therapies. Here, we present urease-powered nanomotors based on mesoporous silica nanoparticles that contain both polyethylene glycol and anti-FGFR3 antibody on their outer surface to target bladder cancer cells in the form of 3D spheroids. The autonomous motion is promoted by urea, which acts as fuel and is inherently present at high concentrations in the bladder. Antibody-modified nanomotors were able to swim in both simulated and real urine, showing a substrate-dependent enhanced diffusion. The internalization efficiency of the antibody-modified nanomotors into the spheroids in the presence of urea was significantly higher compared with antibody-modified passive particles or bare nanomotors. Furthermore, targeted nanomotors resulted in a higher suppression of spheroid proliferation compared with bare nanomotors, which could arise from the local ammonia production and the therapeutic effect of anti-FGFR3. These results hold significant potential for the development of improved targeted cancer therapy and diagnostics using biocompatible nanomotors.
The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we ...report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules (Ru(bpy)3Cl2 (bpy = 2,2′-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both Ru(bpy)3Cl2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to “sense” the environment and deliver the payload on demand in response to predefined stimuli.
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•Scale-up of SPIONs to 3g/batch with a multi-mode microwave unit is demonstrated.•SPIONs are dispersible in water, monodisperse with high saturation magnetization.•Energy and ...cost-efficient scaled-up microwave-assisted SPIONs synthesis is validated.
We report the multi-gram production of water-dispersible superparamagnetic iron oxide nanoparticles (SPIONs) by microwave-assisted reaction. A laboratory-scale reaction performed in a single-mode microwave unit (4.5mL, producing 22mg of Fe2O3) was scaled-up in a multi-mode equipment (up to 500mL, corresponding to 2.61g Fe2O3). The quality of the final material in terms of size, colloidal stability and magnetic properties, and the yield of the reaction (∼80%) were not compromised in the large-scale setup. Hence, these results reinforce the potential of microwave irradiation in industrial laboratories to synthesize high quality nanoparticles readily dispersible in water and in a short time.
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► Triflusal can be impregnated using supercritical CO2 in silica aerogel type materials and PMMA matrices. ► Silica aerogel-based matrices stabilize the drug in molecular form. ► ...Carboxylic H-bonding was determined to be the most feasible conformation for triflusal adsorbed in these matrices. ► Silica aerogels act as a moisture protection barrier for triflusal when compared with PMMA. ► In vitro studies showed a sustained release in the polymer, while a bioavailability increase was obtained for aerogels.
Facile and robust fabrication methodologies of complex materials with high added value for controlled drug delivery systems are highly sought-after in the pharmaceutical industry. Here, we have relied on the use of supercritical fluids for the matrix synthesis as well as for the drug impregnation process. As a model system of a hydrophobic and moisture sensitive active agent, triflusal was impregnated in different aerogel and polymeric matrices using supercritical CO2. In vitro release profiles of drug carriers consisting of SiO2 aerogels as mesoporous monoliths and as microporous nanospheres loaded with triflusal are reported and compared to a more conventional polymeric system (PMMA). Silica-based matrices are found to prevent the hydrolization of the active ingredient more efficiently than the polymeric matrix and displayed much faster release kinetics. Moreover, the triflusal is dispersed in a molecular form inside the silica-based materials. Such features are considered of great interest to enhance the bioavailability of low solubility drugs.
A novel and convenient synthetic strategy for the preparation of magnetically responsive silica nanospheres decorated with mixed ligand protected gold nanoparticles is described. Gold nanoparticles ...are attached to the silica surface via stable amide bond formation. The hierarchical nanospheres show promising results as reusable and efficient catalysts for esterification reactions and they can be recovered through a simple magnetic separation.
The overall objective of the present work was to modulate the release behavior of drug-impregnated silica particles from almost instantaneous release to a more sustained delivery, prolonged during ...several hours. Triflusal was chosen as a model drug of the low biodisponibility type. The process is based in the coating with Eudragit® RL 100 polymer of aerogel-like silica particles. Materials were processed in compressed CO
2
by using the batch and semicontinuous antisolvent coating methods. Triflusal release from Eudragit-coated aerogel particles was compared with the dissolution profiles recorded for pristine triflusal and for triflusal impregnated into polymer or non-coated aerogel particles. The release profiles were determined by high-performance liquid chromatography. Eudragit-coated materials presented an intermediate drug-release rate between this obtained for the infused polymer and that of the impregnated aerogel particles. Diffusion-governed mechanisms were found for the studied aerogel-like systems after fitting the release data to both Korsmeyer-Peppas and Baker-Lonsdale equations. The major advantage of the compressed CO
2
antisolvent approach was the ability to physically coat very fine particles (<100 nm). Moreover, the stability of the studied drug in water increased after coating.
Figure
Schematic representation of the antisolvent CO
2
particle coating and release behavior of the obtained hybrid products
A novel and convenient synthetic strategy for the preparation of magnetically responsive silica nanospheres decorated with mixed ligand protected gold nanoparticles is described. Gold nanoparticles ...are attached to the silica surface
via
stable amide bond formation. The hierarchical nanospheres show promising results as reusable and efficient catalysts for esterification reactions and they can be recovered through a simple magnetic separation.
We have developed hierarchical Fe
2
O
3
@SiO
2
@Au nanospheres and we have demonstrated their use as efficient and easily recoverable catalysts in the conversion of benzyl alcohol to benzyl acetate.
Three different powdered hybrid inorganic-organic composites for pharmaceutical use have been successfully obtained using CO sub(2) as an antisolvent in a batch mode process. Naproxen was chosen as ...the hydrophobic Class II model drug, for which its dissolution rate in water must be enhanced. As excipients, two kind of commercial lipids (G44/14 and G50/13) and a mixture of Eudragit RS100 and Eudragit RL100 polymers were used. Silica microparticles have also been incorporated into the formulation to restrict the naproxen crystals growth and to obtain a powdered material with appropriate micromeritic properties. The morpho-chemical characteristics of these microcomposites and their different release profiles are reported. Importantly, the components have not suffered structural or chemical modifications during the processing and no specific chemical bonds were detected between them. High drug loading has been achieved in the three cases. Water dissolution of the drug formulations is controlled mainly by the wetting properties and nature of the excipients and by the size of the crystals. Among the materials prepared, samples made with Gelucires (hydrophilic species) result in the fastest release of naproxen. We thus conclude that lipid-based ternary formulations display a synergetically accelerated release compared to binary mixtures.
The present work is concerned with host-guest processes in the micro- and mesoporous restricted spaces provided by silica aerogels and aluminosilicates. A supercritical carbon dioxide ...ship-in-a-bottle approach was used for the synthesis of photoactive molecules (triphenylpyrylium and dimethoxyltrityl cations) inside these nanoporous matrices. The resulting hybrid nanocomposites can act as stable and recoverable heterogeneous photocatalysts, having obvious advantages with respect to the more easily degraded organic cations frequently used in homogeneous catalysis. Two aspects of green chemistry are combined in this study to produce nanoporous materials loaded with cationic photosensitizers: (i) the use of supercritical carbon dioxide as a reaction medium in one-pot and as a zero waste technology, and (ii) the use of transparent high surface area nanoporous supports that are expected to be more effective for the target photoactive applications than traditional opaque microporous matrices.
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