Exploring Factors for the Design of Nanoparticles as Drug Delivery Vectors.

To achieve optimal results when employing nanoparticles in biomedical fields, choosing the right type of nanoparticle and determining the correct procedure for drug loading are key factors. Each type of nanoparticle presents a determined set of characteristics that are, in some cases, unique. In general, their surface charge, geometry or hydrophilic character may be limiting factors, depending on what their intended application is. Once synthesized, additional factors, such as their interaction with biological systems and liberation mechanisms into the target cells, also need to be taken into account. Multiple advantages arise from the use of nanoparticles, such as the capability to solubilize hydrophobic compounds and an increased bioavailability. Those advantages justify the extensive and delicate study that should be undertaken in order to use them as drug delivery agents. One of the most important factors for the design of a drug delivery system with nanoparticles is achieving a high drug-to-nanoparticle ratio. In this Minireview, all of these key factors, both physicochemical and biological, are described, and special emphasis is placed on loading methods employed to introduce drugs into nanoparticles.

Covalent and Non-Covalent DNA-Gold-Nanoparticle Interactions: New Avenues of Research.

The interactions of DNA, whether long, hundred base pair chains or short-chained oligonucleotides, with ligands play a key role in the field of structural biology. Its biological activity not only depends on the thermodynamic properties of DNA-ligand complexes, but can and often is conditioned by the formation kinetics of those complexes. On the other hand, gold nanoparticles have long been known to present excellent biocompatibility with biomolecules and are themselves remarkable for their structural, electronic, magnetic, optical and catalytic properties, radically different from those of their counterpart bulk materials, and which make them an important asset in multiple applications. Therefore, thermodynamic and kinetic studies of the interactions of DNA with nanoparticles acting as small ligands are key for a better understanding of those interactions to allow for their control and modulation and for the opening of new venues of research in nanomedicine, analytic and biologic fields. The interactions of gold nanoparticles with both DNA polymers and their smaller subunits; special focus is placed on those interactions taking place with nonfunctionalized gold nanoparticles are reviewed in the present work.

Understanding and improving aggregated gold nanoparticle/dsDNA interactions by molecular spectroscopy and deconvolution methods.

It is well known that single-stranded DNA (ssDNA) is easily able to adsorb on citrate-capped, non-functionalized gold nanoparticles (AuNPs). However, the affinity of double-stranded DNA (dsDNA) for them is much more limited. The present work demonstrates that long dsDNA suffers from a bending conformational change when anionic nanoparticles are present in solution. A striking decrease in the persistence length of the double helix in the absence of salt is observed through dynamic light scattering (DLS), viscometric, and atomic force microscopy (AFM) methods. Long dsDNA is therefore shown to be able to interact with anionic gold nanoparticles. To date, only ssDNA detection has been described by making use of interparticle cross-linking aggregation mechanisms; however, the data shown in this work allow for the development of new methods for detecting dsDNA in solution by using aggregated AuNPs as a starting point. The aggregation state is induced by the controlled addition of an inert electrolyte. A deconvolution procedure of the experimental plasmon shows how individual bands corresponding to aggregated nanoclusters diminish as the DNA concentration increases in the presence of 0.075 M NaCl.

Electrochemiluminescent (ECL) [Ru(bpy)3](2+)/PAMAM dendrimer reactions: coreactant effect and 5-fluorouracil/dendrimer complex formation.

Electrogenerated chemiluminescence (ECL) reactions between tris(2,2'-bipyridine)ruthenium(II) and PAMAM dendrimers of the full (G1.0) and half (G1.5) generations were carried out in an aqueous medium at pH 6.1 and 10.0. In the absence of 5-fluoro-1H,3H-pyrimidine-2,4-dione (5-fluorouracil, 5-Fu) (coreactant effect study), the ECL efficiency trends as a function of [G1.0] and [G1.5] at pH 6.1 and 10.0 revealed that PAMAM dendrimers are about 100 (G1.5, pH 6.1), 60 (G1.5, pH 10.0), 26 (G1.0, pH 10.0) and 13 (G1.0, pH 6.1) times more efficient as ECL coreactants than oxalate anion is. Moreover, ECL reactions were done in the presence of several solutions of 5-Fu at a fixed concentration of the G1.0 and G1.5 dendrimers at pH 6.1 and 10.0 (binding study). The ECL efficiency trends as a function of [5-Fu] highlighted a dendrimer/5-Fu binding. Therefore, one of the most remarkable and novel findings of this work is the potential of PAMAM dendrimers to be used as both sensors and biosensors in an aqueous medium in the presence of a suitable sensitizer. Redox potentials of the [Ru(bpy)3](3+/2+) couple were also determined in the absence and presence of 5-Fu at both pHs. In the absence of 5-Fu the positive or negative shift of redox potentials showed the influence of the repulsive or attractive electrostatic long-range and short-range interactions between the charged dendrimer surface and the oxidized and reduced forms of the couple. In the presence of 5-Fu the trends of redox potentials highlighted the existence of a charged dendrimer/5-Fu species. Graphical Abstract ECL emission for the [Ru(bpy)3](2+)/ G1.0 dendrimer reaction in the presence of the 5-Fu at pH 6.1.

Nonfunctionalized Gold Nanoparticles: Synthetic Routes and Synthesis Condition Dependence.

Since Faraday first described gold sol synthesis, synthetic routes to nanoparticles, as well as their applications, have experienced a huge growth. Variations in synthesis conditions such as pH, temperature, reduction, and the stabilizing agent used will determine the morphology, size, monodispersity, and stability of nanoparticles obtained, allowing for modulation of their physical and chemical properties. Although many studies have been made about the synthesis and characterization of individual nanosystems of interest, to our knowledge the common, general traits that all those synthesis share have not been previously compiled. In this review, we aim to offer a global vision of some of the most relevant synthetic procedures reported up to date, with a special focus on nonfunctionalized gold nanoparticle synthetic routes in aqueous media, and to display a broad overview of the influence that synthesis conditions have on the shape, stability, and reactivity of nanoparticle systems.

Colorimetric, Naked-Eye Detection of Lysozyme in Human Urine with Gold Nanoparticles.

The stabilizing effect of lysozymes to salt addition over a gold colloid are exploited in order to detect lysozymes in human urine samples. The present research is aimed at the development of a fast, naked-eye detection test for urinary lysozymuria, in which direct comparison with a colorimetric reference, allows for the immediate determination of positive/negative cases. CIEL*a*b* parameters were obtained from sample absorbance measurements, and their color difference with respect to a fixed reference point was measured by calculating the ΔE76 parameter, which is a measure of how well the colors can be distinguished by an untrained observer. Results show that a simple and quick test can reliably, in less than 15 min, give a positive colorimetric response in the naked eye for concentrations of a urinary lysozyme over 57.2 µg/mL. This concentration is well within the limits of that observed for leukemia-associated lysozymurias, among other disorders.

Lysozyme-AuNPs Interactions: Determination of Binding Free Energy.

Investigation and optimization of lysozyme (Lys) adsorption onto gold nanoparticles, AuNPs, were carried out. The purpose of this study is to determine the magnitude of the AuNPs-lysozyme interaction in aqueous media by simple spectrophotometric means, and to obtain the free energy of binding of the system for the first time. In order to explore the possibilities of gold nanoparticles for sensing lysozyme in aqueous media, the stability of the samples and the influence of the gold and nanoparticle concentrations in the detection limit were studied. ζ potential measurements and the shift of the surface plasmon band showed a state of saturation with an average number of 55 Lys per gold nanoparticle. Lysozyme-AuNPs interactions induce aggregation of citrate-stabilized AuNPs at low concentrations by neutering the negative charges of citrate anions; from those aggregation data, the magnitude of the interactions has been measured by using Benesi-Hildebrand plots. However, at higher protein concentrations aggregation has been found to decrease. Although the nanocluster morphology remains unchanged in the presence of Lys, slight conformational changes of the protein occur. The influence of the size of the nanoclusters was also investigated for 5, 10, and 20 nm AuNPs, and 10 nm AuNPs was found the most appropriate.

Encased Gold Nanoparticle Synthesis as a Probe for Oleuropein Self-Assembled Structure Formation.

Stable oleuropein-coated gold nanoparticles in aqueous media were synthesized for the first time. Oleuropein (OLE) concentration in the reaction medium was found to greatly influence the outcome and stability of the resulting nanocolloid, with a marked decrease in particle size being found for the more concentrated oleuropein solutions. The protection mechanisms involved in the stabilized nanosystems were analyzed. Oleuropein self-assembled structures were found to be formed at a concentration threshold of [OLE] > 5 × 10-5 M, and observed through the use of CryoSEM imaging. Those structures were responsible for both the increased stability and the decrease in size observed at the more concentrated solutions.

Author Correction: Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing.

Nowadays there is a worldwide growing interest in the Inkjet Printing technology owing to its potentially high levels of geometrical complexity, personalization and resolution. There is also social concern about usage, disposal and accumulation of plastic materials. In this work, it is shown that sugar-based biodegradable polyurethane polymers exhibit outstanding properties as polymer-matrix for gold nanoparticles composites. These materials could reach exceptional stabilization levels, and demonstrated potential as novel robust inks for Inkjet based Printing. Furthermore, a physical comparison among different polymers is discussed based on stability and printability experiments to search for the best ink candidate. The University of Seville logo was printed by employing those inks, and the presence of gold was confirmed by ToF-SIMS. This approach has the potential to open new routes and applications for fabrication of enhanced biomedical nanometallic-sensors using stabilized AuNP.