A Colorimetric Test to Differentiate Patients Infected with Influenza from COVID-19.

Patients infected with SARS-CoV-2 and influenza display similar symptoms, but treatment requirements are different. Clinicians need to accurately distinguish SARS-CoV-2 from influenza to provide appropriate treatment. Here, the authors develope a color-based technique to differentiate between patients infected with SARS-CoV-2 and influenza A using a nucleic acid enzyme-gold nanoparticle (GNP) molecular test requiring minimal equipment. The MNAzyme and GNP probes are designed to be robust to viral mutations. Conserved regions of the viral genomes are targeted, and two MNAzymes are created for each virus. The ability of the system to distinguish between SARS-CoV-2 and influenza A using 79 patient samples is tested. When detecting SARS-CoV-2 positive patients, the clinical sensitivity is 90%, and the specificity is 100%. When detecting influenza A, the clinical sensitivity and specificity are 93% and 100%, respectively. The high clinical performance of the MNAzyme-GNP assay shows that it can be used to help clinicians choose effective treatments.

Diagnosing Antibiotic Resistance Using Nucleic Acid Enzymes and Gold Nanoparticles.

The rapid and accurate detection of antimicrobial resistance is critical to limiting the spread of infections and delivering effective treatments. Here, we developed a rapid, sensitive, and simple colorimetric nanodiagnostic platform to identify disease-causing pathogens and their associated antibiotic resistance genes within 2 h. The platform can detect bacteria from different biological samples (i.e., blood, wound swabs) with or without culturing. We validated the multicomponent nucleic acid enzyme-gold nanoparticle (MNAzyme-GNP) platform by screening patients with central line associated bloodstream infections and achieved a clinical sensitivity and specificity of 86% and 100%, respectively. We detected antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) in patient swabs with 90% clinical sensitivity and 95% clinical specificity. Finally, we identified mecA resistance genes in uncultured nasal, groin, axilla, and wound swabs from patients with 90% clinical sensitivity and 95% clinical specificity. The simplicity and versatility for detecting bacteria and antibiotic resistance markers make our platform attractive for the broad screening of microbial pathogens.

Nanoparticle Uptake in a Spontaneous and Immunocompetent Woodchuck Liver Cancer Model.

There is a tremendous focus on the application of nanomaterials for the treatment of cancer. Nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. However, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. We introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (NP)-based in vivo experiments. Liver cancer development in these out-bred animals occurs as a result of persistent viral infection, mimicking human hepatitis B virus-induced HCC development. We highlight how this model addresses key gaps associated with other commonly used tumor models. We employed this model to (1) track organ biodistribution of gold NPs after intravenous administration, (2) examine their subcellular localization in the liver, (3) determine clearance kinetics, and (4) characterize the identity of hepatic macrophages that take up NPs using RNA-sequencing (RNA-seq). We found that the liver and spleen were the primary sites of NP accumulation. Subcellular analyses revealed accumulation of NPs in the lysosomes of CD14+ cells. Through RNA-seq, we uncovered that immunosuppressive macrophages within the woodchuck liver are the major cell type that take up injected NPs. The woodchuck-HCC model has the potential to be an invaluable tool to examine NP-based immune modifiers that promote host anti-tumor immunity.

A versatile plasmonic thermogel for disinfection of antimicrobial resistant bacteria.

The increasing occurrence of antimicrobial resistance among bacteria is a global problem that requires the development of alternative techniques to eradicate these superbugs. Herein, we used a combination of thermosensitive biocompatible polymer and gold nanorods to specifically deliver, preserve and confine heat to the area of interest. Our data demonstrates that this technique can be used to kill both Gram positive and Gram negative antimicrobial resistant bacteria in vitro. Our approach significantly reduces the antimicrobial resistant bacteria load in experimentally infected wounds by 98% without harming the surrounding tissues. More importantly, this polymer-nanocomposite can be prepared easily and applied to the wounds, can generate heat using a hand-held laser device, is safe for the operator, and does not have any adverse effects on the wound tissue and healing process.