Mateus Borba Cardoso

Size-selective silver nanoparticles: future of biomedical devices with enhanced bactericidal properties

Silver nanoparticles (AgNPs) are attracting attention due to their bactericidal activity and consequent possible biomedical applications. The key to their broad-acting and potent biocidal property seems to be based on the size-related mechanism by which AgNPs act on different bacteria strains. Here, we report the synthesis and successful size-selective fractionation of AgNPs obtained through chemical reduction of silver nitrate in ethylene glycol using polyvinylpyrrolidone as a protective agent. A combination of characterization techniques (UV-vis spectroscopy, transmission electron microscopy and small-angle X-ray scattering) is employed to differentiate the two size-fractionated samples. From the analyses, it is evidenced that AgNPs are mainly spherical and have their radius centered at ∼8.5 and ∼11.0 nm. The nanoparticles bactericidal efficacy is investigated using the disk diffusion test against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Micrococcus lysodeikticus. Although both fractionated samples present bactericidal activity against all four tested bacteria (one Gram negative and three Gram positives), those presenting smaller size own enhanced antibacterial properties.

Tailored Silica-Antibiotic Nanoparticles: Overcoming Bacterial Resistance with Low Cytotoxicity

New and more aggressive antibiotic resistant bacteria arise at an alarming rate and represent an ever-growing challenge to global health care systems. Consequently, the development of new antimicrobial agents is required to overcome the inefficiency of conventional antibiotics and bypass treatment limitations related to these pathologies. In this study, we present a synthesis protocol, which was able to entrap tetracycline antibiotic into silica nanospheres. Bactericidal efficacy of these structures was tested against bacteria that were susceptible and resistant to antibiotics. For nonresistant bacteria, our composite had bactericidal efficiency comparable to that of free-tetracycline. On the other hand, the synthesized composites were able to avoid bacterial growth of resistant bacteria while free-tetracycline has shown no significant bactericidal effect. Finally, we have investigated the cytotoxicity of these nanoparticles against mammalian cells to check any possible poisoning effect. It was found that these nanospheres are not apoptosis-inducers and only a reduction on the cell replication rate was seen when compared to the control without nanoparticles.

Functionalized Silica Nanoparticles As an Alternative Platform for Targeted Drug-Delivery of Water Insoluble Drugs

The selective action of drugs in tumor cells is a major problem in cancer therapy. Most chemotherapy drugs act nonspecifically and damage both cancer and healthy cells causing various side effects. In this study, the preparation of a selective drug delivery system, which is able to act as a carrier for hydrophobic and anticancer drugs is reported. Amino-functionalized silica nanoparticles loaded with curcumin were successfully synthesized via sol-gel approach and duly characterized. Thereafter, the targeting ligand, folate, was covalently attached to amino groups of nanoparticle surface through amide bond formation. The cytotoxic effect of nanoparticles on prostate cancer cells line was evaluated and compared to normal cells line (prostate epithelial cell). Cytotoxicity experiments demonstrated that folate-functionalized nanoparticles were significantly cytotoxic to tumor cells, whereas normal cells were much less affected by the presence of these structures.

Partial aggregation of silver nanoparticles induced by capping and reducing agents competition.

It is well known that nanomaterials properties and applications are dependent on the size, shape, and morphology of these structures. Among nanomaterials, silver nanoparticles (AgNPs) have attracted attention since they have considerably versatile properties, such as a variable surface area to volume ratio, which is very useful for many biomedical and technological applications. Within this scenario, small nanoparticle aggregates can have their properties reduced due to the increased size and alterations in their shape/morphology. In this work, silver nanoparticles aggregation was studied through chemical reduction of silver nitrate in the presence of sodium borohydride (reducing agent) and sodium citrate (capping agent). By changing the amount of reducing agent along the reaction, unaggregated and partially aggregated samples were obtained and characterized by UV-vis, zeta potential, and SAXS techniques. pH was measured in every step of the reaction in order to correlate these results with those obtained from structural techniques. Addition of the reducing agent first causes the reduction of Ag(+) to silver nanoparticles. For higher concentrations of sodium borohydrate, the average AgNPs size is increased and NPs aggregation is observed. It was found that zeta potential and pH values have a strong influence on AgNPs formation, since reducing agent addition can induce partial removal of citrate weakly associated on the AgNPs surface and increase the ionic strength of the solution, promoting partial aggregation of the particles. This aggregation state was duly identified by coupling SAXS, zeta potential and pH measurements. In addition, the SAXS technique showed that aggregates formed along the process are elongated-like particles due to the exponential decay evidenced through SAXS curves.

Optical paper-based sensor for ascorbic acid quantification using silver nanoparticles

In this paper, we demonstrate for the first time the use of silver nanoparticles (AgNPs) for colorimetric ascorbic acid (AA) quantification in a paper-based sensor. This device is constituted by spot tests modified with AgNPs and silver ions bordered by a hydrophobic barrier which provides quantitative and fast analysis of AA. In addition, this device is employed as point-of-care monitoring using a unique drop of the sample. AgNPs paper-based sensor changed from light yellow to gray color after the addition of AA due to nanoparticle growth and clusters formation. The color intensities were altered as a function of AA concentration which were measured by either a scanner or a homemade portable transmittance colorimeter. Under the selected measurement conditions, results presented limit of detection which was comparable to analytical laboratory-based methodologies. In addition, the sensitivity of our sensor was comparable to the standard titration method when real samples were investigated.

Three-dimensional non-destructive soft-tissue visualization with X-ray staining micro-tomography.

Low inherent contrast in soft tissues has been limiting the use of X-ray absorption micro-computed tomography (micro-CT) to access high-resolution structural information of animal organs. The staining agents used in micro-CT to improve the contrast fail in providing high-quality images of whole organs of animals due to diffusion problems of the staining agent into the sample. We demonstrate a staining protocol that incorporates a biochemical conditioning step prior to exposure to the staining agent that succeeds in overcoming the diffusion problems, thus quickly providing high-quality micro-CT images of whole organs of mammals. Besides of yielding non-distorted three-dimensional information at the same spatial resolution accessible in histological sections, micro-CT images of whole organs stained by our method enable easy screening of slices along any direction of the volume thus demonstrating new possibilities of structural analysis in biomedical science.

Silica imprinted materials containing pharmaceuticals as a template: textural aspects

Silica-based materials were prepared by the acid catalyzed sol–gel method using different pharmaceuticals as a template. The template molecules investigated were fluoxetine, gentamicin, lidocaine, morphine, nifedipine, paracetamol and tetracycline. The resulting hybrid silicas underwent ultrasound extraction in the presence of several solvents and were characterized by elemental analysis, porosimetry by adsorption/desorption of nitrogen (BET method), small-angle X-ray scattering and X-ray diffraction. Drug extraction was carried out by the combination of solvent and ultra-sound. The textural characteristics of the hybrid xerogels and resulting imprinted materials were shown to be highly dependent on the molecular weight and molecular volume of the drug template. Increasing the molecular weight of the template results in a decrease in the encapsulation content of the resulting material. In the case of paracetamol and fluoxetine, the dimensions of the surface area are not sufficient to guarantee the adsorption of the smaller molecule. Instead, the shape generated through encapsulation and extraction during the production of the imprinted silica dictates the adsorption behavior.

Mechanism of interaction between colloids and bacteria as evidenced by tailored silica–lysozyme composites

The ever increasing antibiotic resistance levels in pathogenic and non-pathogenic bacteria have boosted the search for effective controlling methods of bacterial infections. In this context, we prepared colloidal silica–lysozyme composites to evaluate the interaction between these structures and bacteria. Lysozyme was chosen since it is a protein that holds bactericidal properties and that, in the reaction process, acts as a catalyst which favors silica hydrolysis and condensation. The high entrapment yield of lysozyme in the silica cage (approximately 95%) does not change the secondary structure of the protein resulting in a material with superior bactericidal properties. The antimicrobial differences when silica–lysozyme composites are tested against Escherichia coli and Staphylococcus aureus are used to propose an interaction mechanism between colloids and bacteria. Bactericidal properties of the composites are attributed to the ultra-structural organization of the composite which, due to the positive surface charge, is attracted by the negative bacterial cell wall while lysozyme is delivered.

Doxycycline conjugated with polyvinylpyrrolidone-encapsulated silver nanoparticles: a polymer's malevolent touch against Escherichia coli

The emergence of multi-resistant pathogens has necessitated the investigation of new strategies to cope with this ever-increasing threat to public health. In this context, we combined silver nanoparticles (AgNPs) with doxycycline (DO), an antibiotic from the class of tetracyclines, to evaluate the potentiality of this hybrid as a bactericidal agent against E. coli. Polyvinylpyrrolidone (PVP) was used as a stabilizer to prevent the excessive growth and agglomeration of AgNPs. Interestingly, DO bound directly to PVP and had its concentration increased around the particle as a consequence of this interaction. As a result, the AgNPs/DO conjugates presented enhanced bactericidal properties compared to the individual components. Stabilizing agents are generally unwanted on the surfaces of nanoparticles because of their potential to block adsorption surface sites. However, we have shown that PVP played a paramount role in concentrating DO around the particle, which culminated in an increased bactericidal activity towards E. coli.

Viral Inhibition Mechanism Mediated by Surface-Modified Silica Nanoparticles

Vaccines and therapies are not available for several diseases caused by viruses, thus viral infections result in morbidity and mortality of millions of people every year. Nanoparticles are considered to be potentially effective in inhibiting viral infections. However, critical issues related to their use include their toxicity and their mechanisms of antiviral action, which are not yet completely elucidated. To tackle these problems, we synthesized silica nanoparticles with distinct surface properties and evaluated their biocompatibility and antiviral efficacy. We show that nanoparticles exhibited no significant toxicity to mammalian cells, while declines up to 50% in the viral transduction ability of two distinct recombinant viruses were observed. We designed experiments to address the mechanism of antiviral action of our nanoparticles and found that their hydrophobic/hydrophilic characters play a crucial role. Our results reveal that the use of functionalized silica particles is a promising approach for controlling viral infection and offer promising strategies for viral control.