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)3]Cl2 (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)3]Cl2 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.
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.
ABSTRACT:The overall objective of the present study was to modulate the surface characteristics of aerogel-like submicron and nanometric particles by coating them with polyethyleneimine (PEI) to suit specific biological applications. A new process for the covalent grafting of low-molecular weight PEI chains has been described, based on the use of compressed CO 2 as the initiator of the ring opening polymerization of the ethyleneimine monomer, which was performed in the presence of silica particles. Coating was done at low pressure and temperature and in the absence of any organic solvent. Obtained materials were compared with a product prepared following the standard soaking procedure for PEI coating. Materials were characterized regarding composition, structure, surface charge, particle size, morphology, and drug release. The developed process led to the covalent grafting of low-molecular weight PEI on the silica surface, which conferred an increased thermal stability for the coating and low cytotoxicity to the particles.
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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