Gold Nanoparticles Capped with a Novel Titanium(IV)-Containing Polyoxomolybdate Cluster: Selective and Enhanced Bactericidal Effect Against Escherichia coli.

Bacterial infections are a public health threat of increasing concern in medical care systems; hence, the search for novel strategies to lower the use of antibiotics and their harmful effects becomes imperative. Herein, the antimicrobial performance of four polyoxometalate (POM)-stabilized gold nanoparticles (Au@POM) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as Gram-negative and Gram-positive bacteria models, respectively, is studied. The bactericidal studies performed, both in planktonic and sessile forms, evidence the antimicrobial potential of these hybrid nanostructures with selectivity toward Gram-negative species. In particular, the Au@GeMoTi composite with the novel [Ti2 (HGeMo7 O28 )2 ]10- POM capping ligand exhibits outstanding bactericidal efficiency with a minimum inhibitory concentration of just 3.12 µm for the E. coli strain, thus outperforming the other three Au@POM counterparts. GeMoTi represents the fourth example of a water-soluble TiIV -containing polyoxomolybdate, and among them, the first sandwich-type structure having heteroatoms in high-oxidation state. The evaluation of the bactericidal mechanisms of action points to the cell membrane hyperpolarization, disruption, and subsequent nucleotide leakage and the low cytotoxicity exerted on five different cell lines at antimicrobial doses demonstrates the antibiotic-like character. These studies highlight the successful design and development of a new POM-based nanomaterial able to eradicate Gram-negative bacteria without damaging mammalian cells.

New insights in osteoarthritis diagnosis and treatment: Nano-strategies for an improved disease management.

Osteoarthritis (OA) is a common chronic joint pathology that has become a predominant cause of disability worldwide. Even though the origin and evolution of OA rely on different factors that are not yet elucidated nor understood, the development of novel strategies to treat OA has emerged in the last years. Cartilage degradation is the main hallmark of the pathology though alterations in bone and synovial inflammation, among other comorbidities, are also involved during OA progression. From a molecular point of view, a vast amount of signaling pathways are implicated in the progression of the disease, opening up a wide plethora of targets to attenuate or even halt OA. The main purpose of this review is to shed light on the recent strategies published based on nanotechnology for the early diagnosis of the disease as well as the most promising nano-enabling therapeutic approaches validated in preclinical models. To address the clinical issue, the key pathways involved in OA initiation and progression are described as the main potential targets for OA prevention and early treatment. Furthermore, an overview of current therapeutic strategies is depicted. Finally, to solve the drawbacks of current treatments, nanobiomedicine has shown demonstrated benefits when using drug delivery systems compared with the administration of the equivalent doses of the free drugs and the potential of disease-modifying OA drugs when using nanosystems. We anticipate that the development of smart and specific bioresponsive and biocompatible nanosystems will provide a solid and promising basis for effective OA early diagnosis and treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

Elucidating the mechanisms of action of antibiotic-like ionic gold and biogenic gold nanoparticles against bacteria.

The antimicrobial action of gold depends on different factors including its oxidation state in the intra- and extracellular medium, the redox potential, its ability to produce reactive oxygen species (ROS), the medium components, the properties of the targeted bacteria wall, its penetration in the bacterial cytosol, the cell membrane potential, and its interaction with intracellular components. We demonstrate that different gold species are able to induce bacterial wall damage as a result of their electrostatic interaction with the cell membrane, the promotion of ROS generation, and the consequent DNA damage. In-depth genomic and proteomic studies on Escherichia coli confirmed the superior toxicity of Au (III) vs Au (I) based on the different molecular mechanisms analyzed including oxidative stress, bacterial energetic metabolism, biosynthetic processes, and cell transport. At equivalent bactericidal doses of Au (III) and Au (I) eukaryotic cells were not as affected as bacteria did, maintaining unaffected cell viability, morphology, and focal adhesions; however, increased ROS generation and disruption in the mitochondrial membrane potential were also observed. Herein, we shed light on the antimicrobial mechanisms of ionic and biogenic gold nanoparticles against bacteria. Under selected conditions antibiotic-like ionic gold can exert a strong antimicrobial activity while being harmless to human cells.

Anti-Inflammatory and Chondroprotective Effects Induced by Phenolic Compounds from Onion Waste Extracts in ATDC-5 Chondrogenic Cell Line.

Osteoarthritis is a prevalent degenerative condition that is closely related to the destruction and inflammation of cartilage. The high prevalence of this pathology exhorts researchers to search for novel therapeutic approaches. Vegetable-fruit wastes have emerged as a promising origin of anti-inflammatory and antioxidant compounds that, in some cases, may also exert chondroprotective effects. This study aims to decipher the potential of onion waste products in the inhibition of molecular events involved in osteoarthritis. Onion extracts showed a high content of phenolic compounds and antioxidant properties. Cytocompatibility was demonstrated in the chondrogenic cell line ATDC-5, exerting viability percentages higher than 90% and a slight increase in the S phase cycle cell. The induction of inflammation mediated by the lipopolysaccharide and onion extracts' treatment substantially inhibited molecular markers related to inflammation and cartilage degradation, highlighting the promising application of onion extracts in biomedical approaches. The in silico analyses suggested that the results could be attributed to protocatechuic, ellagic, and vanillic acids' greater cell membrane permeability. Our work provides distinctive information about the possible application of waste onion extracts as functional components with anti-inflammatory and chondroprotective characteristics in osteoarthritis.

Valorization of Onion Waste by Obtaining Extracts Rich in Phenolic Compounds and Feasibility of Its Therapeutic Use on Colon Cancer.

In this study, the total phenolic content, the antioxidant and antiproliferative activities of onion waste extracts were characterized. Some phenolic compounds present in the extracts were also identified and quantified by HPLC-DAD. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The onion extract possessed a high amount of phenolic compounds (177 ± 9 mg/g extract) and had an effective antioxidant capacity measured by ABTS, FRAP and DPPH assays. Regarding the antiproliferative activity, the onion extracts produced cell cycle arrest in the S phase with p53 activation, intrinsic apoptosis (mitochondrial membrane potential modification) and caspase 3 activation. Likewise, onion waste increased intracellular ROS with possible NF-kB activation causing a proteasome down regulation. In addition, the extracts protected the intestine against oxidative stress induced by H2O2. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to protocatechuic acid. Therefore, this study provides new insights regarding the potential use of these types of extract as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress, such as cancer. In addition, its valorization would contribute to the circular economy.