Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications.

Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer.

High affinity protein surface binding through co-engineering of nanoparticles and proteins.

Control over supramolecular recognition between proteins and nanoparticles (NPs) is of fundamental importance in therapeutic applications and sensor development. Most NP-protein binding approaches use 'tags' such as biotin or His-tags to provide high affinity; protein surface recognition provides a versatile alternative strategy. Generating high affinity NP-protein interactions is challenging however, due to dielectric screening at physiological ionic strengths.

Impact of COVID-19 on the Intestinal Microbiome.

Purpose Of Review: This review article aims to explore the GI changes induced by SARS-CoV-2 and how gut microbial homeostasis can influence these changes and affect the lung-gut axis and its relationship with the induction of the cytokine release syndrome in severe COVID-19 patients.

Recent Findings: Coronavirus disease 2019 (COVID-19) affects not only the respiratory system but can produce multi-systemic damage. The expression of angiotensin-converting enzyme 2 (ACE-2) receptors in the gastrointestinal (GI) tract, the high prevalence of GI symptoms in severely ill COVID-19 patients, and the abnormalities described in the gut microbiome in these patients have raised concerns about the influence of GI tract as a risk factor or as a potential modulator to reduce the severity of COVID-19.

Nanotherapeutics using all-natural materials. Effective treatment of wound biofilm infections using crosslinked nanoemulsions.

Bacterial wound infections are a threat to public health. Although antibiotics currently provide front-line treatments for bacterial infections, the development of drug resistance coupled with the defenses provided through biofilm formation render these infections difficult, if not impossible, to cure. Antimicrobials from natural resources provide unique antimicrobial mechanisms and are generally recognized as safe and sustainable.

Polymeric Nanoparticles Active against Dual-Species Bacterial Biofilms.

Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species.

High-content and high-throughput identification of macrophage polarization phenotypes.

Macrophages are plastic cells of the innate immune system that perform a wide range of immune- and homeostasis-related functions. Due to their plasticity, macrophages can polarize into a spectrum of activated phenotypes. Rapid identification of macrophage polarization states provides valuable information for drug discovery, toxicological screening, and immunotherapy evaluation.

Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts.

Bioorthogonal catalysis provides a promising strategy for imaging and therapeutic applications, providing controlled in situ activation of pro-dyes and prodrugs. In this work, the use of a polymeric scaffold to encapsulate transition metal catalysts (TMCs), generating bioorthogonal "polyzymes," is presented. These polyzymes enhance the stability of TMCs, protecting the catalytic centers from deactivation in biological media.

Functionalized Polymers Enhance Permeability of Antibiotics in Gram-negative MDR Bacteria and Biofilms for Synergistic Antimicrobial Therapy.

The emergence of multi-drug resistant pathogenic bacteria constitutes a key threat to global health. Infections caused by multi-drug resistant Gram-negative bacteria are particularly challenging to treat due to the ability of pathogens to prevent antibiotic penetration inside the bacterial membrane. Antibiotic therapy is further rendered ineffective due to biofilm formation where the protective Extracellular Polymeric Substance (EPS) matrix limits the diffusion of antibiotics inside the biofilm.

Phytochemical-Based Nanocomposites for the Treatment of Bacterial Biofilms.

Biofilm infections are responsible for at least 65% of human bacterial infections. These biofilms are refractory to conventional antibiotics, leading to chronic infections and nonhealing wounds. Plant-derived antibiotics (phytochemicals) are promising alternative antimicrobial treatments featuring antimicrobial properties.

Rapid Identification of Biofilms Using a Robust Multichannel Polymer Sensor Array.

Infections caused by bacterial biofilms are challenging to diagnose because of the complexity of both the bacteria and the heterogeneous biofilm matrix. We report here a robust polymer-based sensor array that uses selective interactions between polymer sensor elements and the biofilm matrix to identify bacteria species. In this array, an appropriate choice of fluorophore enabled excimer formation and interpolymer FRET, generating six output channels from three polymers.

Water-Dispersible and Biocompatible Iron Carbide Nanoparticles with High Specific Absorption Rate.

Magnetic nanoparticles are important tools for biomedicine, where they serve as versatile multifunctional instruments for a wide range of applications. Among these applications, magnetic hyperthermia is of special interest for the destruction of tumors and triggering of drug delivery. However, many applications of magnetic nanoparticles require high-quality magnetic nanoparticles displaying high specific absorption rates (SARs), which remains a challenge today.

Control of Intra- versus Extracellular Bioorthogonal Catalysis Using Surface-Engineered Nanozymes.

Bioorthogonal transformation of prodrugs and profluorophores using transition metal catalysts (TMCs) offers a promising strategy for therapeutic and imaging applications. Here, we report the surface engineering of nanoparticles to specifically localize gold nanoparticles (AuNPs) with encapsulated TMCs (nanozymes) to either the inside or outside of cells. The ability to control nanozyme localization and hence activity was demonstrated by the activation of pro-fluorophores and prodrugs intra- and extracellularly, establishing the potential of engineered nanozyme platforms for both diagnostic and therapeutic purposes.

Dual Functionalization of Nanoparticles for Generating Corona-Free and Noncytotoxic Silica Nanoparticles.

Protein coronas form on the surfaces of nanomaterials in biological fluids. This layer of proteins affects the properties of nanomaterials, altering their behavior and masking engineered functionality. The use of nonfouling moieties reduces or prevents corona formation; however, these ligands typically complicate functionalization.

Matrix-Incorporated Polydopamine Layer as a Simple, Efficient, and Universal Coating for Laser Desorption/Ionization Time-of-Flight Mass Spectrometric Analysis.

Self-oxidative copolymerization of dopamine with α-cyano-4-hydroxycinnamic acid (CHCA) provides an efficient and multifunctional platform for laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) analysis. The polydopamine coating layer embedded with the CHCA matrix can be readily formed on nanomaterials and solid substrates without additional surface treatments to generate an efficient LDI-TOF-MS platform for the analysis of small molecules as well as synthetic polymers. This coating can be further functionalized with specific ligands for target enrichment from complex biological media, providing analyte capture for subsequent LDI-TOF-MS analysis.

Dynamically crosslinked polymer nanocomposites to treat multidrug-resistant bacterial biofilms.

Multidrug-resistant biofilms are highly resistant to current antimicrobial therapies. We have developed an antimicrobial platform that integrates the bacteria-killing phytochemical carvacrol into dynamically crosslinked polymer nanocomposites (DCPNs). Taking advantage of a reversibly crosslinked Schiff-base scaffold throughout the engineered emulsions, DCPNs exhibited long-term shelf-life and good stability in serum, while readily disassembling in acidic microenvironments.

Engineered Polymer Nanoparticles with Unprecedented Antimicrobial Efficacy and Therapeutic Indices against Multidrug-Resistant Bacteria and Biofilms.

The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semirigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides.

Nanocapsule-mediated cytosolic siRNA delivery for anti-inflammatory treatment.

The use of nanoparticle-stabilized nanocapsules for cytosolic siRNA delivery for immunomodulation in vitro and in vivo is reported. These NPSCs deliver siRNA directly to the cytosol of macrophages in vitro with concomitant knockdown of gene expression. In vivo studies showed directed delivery of NPSCs to the spleen, enabling gene silencing of macrophages, with preliminary studies showing 70% gene knockdown at a siRNA dose of 0.

A Rapid and Robust Diagnostic for Liver Fibrosis Using a Multichannel Polymer Sensor Array.

Liver disease is the fifth most common cause of premature death in the Western world, with the irreversible damage caused by fibrosis, and ultimately cirrhosis, a primary driver of mortality. Early detection of fibrosis would facilitate treatment of the underlying liver disease to limit progression. Unfortunately, most cases of liver disease are diagnosed late, with current strategies reliant on invasive biopsy or fragile lab-based antibody technologies.

Biodegradable Nanocomposite Antimicrobials for the Eradication of Multidrug-Resistant Bacterial Biofilms without Accumulated Resistance.

Infections caused by multidrug-resistant (MDR) bacteria are a rapidly growing threat to human health, in many cases exacerbated by their presence in biofilms. We report here a biocompatible oil-in-water cross-linked polymeric nanocomposite that degrades in the presence of physiologically relevant biomolecules. These degradable nanocomposites demonstrated broad-spectrum penetration and elimination of MDR bacteria, eliminating biofilms with no toxicity to cocultured mammalian fibroblast cells.

Stable and oxidant responsive zwitterionic nanoclusters.

Zwitterions are promising ligands for the fabrication of non-toxic and non-interacting biomaterials. Sulfonamide-based monothiol zwitterionic ligands on gold nanocluster (AuNC) surfaces provide nanomaterials with stable colloidal properties and intense red emission in biological environments. The fluorescence intensity of the nanocluster can be modulated by reactive oxygen species (e.