Combining functionalities-nanoarchitectonics for combatting bacterial infection.

New antimicrobial and anti-inflammatory therapeutics are needed because of antibiotic resistance development and resulting complications such as inflammation, ultimately leading to septic shock. The antimicrobial effects of various nanoparticles (NPs) are currently attracting intensive research interest. Although various NPs display potent antimicrobial effects against strains resistant to conventional antibiotics, the therapeutic use of such materials is restricted by poor selectivity between bacteria and human cells, leading to adverse side effects.

Photocatalytic Degradation of Bacterial Lipopolysaccharides by Peptide-Coated TiO Nanoparticles.

In this study, we report the degradation of smooth and rough lipopolysaccharides (LPS) from Gram-negative bacteria and of lipoteichoic acid (LTA) from Gram-positive bacteria by peptide-coated TiO nanoparticles (TiO NPs). While bare TiO NPs displayed minor binding to both LPS and LTA, coating TiO NPs with the antimicrobial peptide LL-37 dramatically increased the level of binding to both LPS and LTA, decorating these uniformly. Importantly, peptide coating did not suppress reactive oxygen species generation of TiO NPs; hence, UV illumination triggered pronounced degradation of LPS and LTA by peptide-coated TiO NPs.

Stimuli-responsive drug delivery systems for inflammatory skin conditions.

Inflammatory skin conditions highly influence the quality of life of the patients suffering from these disorders. Symptoms include red, itchy and painful skin lesions, which are visible to the rest of the world, causing stigmatization and a significantly lower mental health of the patients. Treatment options are often unsatisfactory, as they suffer from either low patient adherence or the risk of severe side effects.

Matrix metalloproteinase landscape in the imiquimod-induced skin inflammation mouse model.

Inflammation and autoimmunity are known as central processes in many skin diseases, including psoriasis. It is therefore important to develop pre-clinical models that describe disease-related aspects to enable testing of pharmaceutical drug candidates and formulations. A widely accepted pre-clinical model of psoriasis is the imiquimod (IMQ)-induced skin inflammation mouse model, where topically applied IMQ provokes local skin inflammation.

Neutron reflectometry as a powerful tool to elucidate membrane interactions of drug delivery systems.

The last couple of decades have seen an explosion of novel colloidal drug delivery systems, which have been demonstrated to increase drug efficacy, reduce side-effects, and provide various other advantages for both small-molecule and biomacromolecular drugs. The interactions of delivery systems with biomembranes are increasingly recognized to play a key role for efficient eradication of pathogens and cancer cells, as well as for intracellular delivery of protein and nucleic acid drugs. In parallel, there has been a broadening of methodologies for investigating such systems.

Boosting Membrane Interactions and Antimicrobial Effects of Photocatalytic Titanium Dioxide Nanoparticles by Peptide Coating.

Photocatalytic nanoparticles offer antimicrobial effects under illumination due to the formation of reactive oxygen species (ROS), capable of degrading bacterial membranes. ROS may, however, also degrade human cell membranes and trigger toxicity. Since antimicrobial peptides (AMPs) may display excellent selectivity between human cells and bacteria, these may offer opportunities to effectively "target" nanoparticles to bacterial membranes for increased selectivity.

Pulmonary delivery systems for antimicrobial peptides.

Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1) bacterial infection is the main cause of disease (e.g.

Bioactive Suture with Added Innate Defense Functionality for the Reduction of Bacterial Infection and Inflammation.

Surgical site infections (SSI) are a clinical and economic burden. Suture-associated SSI may develop when bacteria colonize the suture surface and form biofilms that are resistant to antibiotics. Thrombin-derived C-terminal peptide (TCP)-25 is a host defense peptide with a unique dual mode of action that can target both bacteria and the excessive inflammation induced by bacterial products.

Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery.

Protease-responsive multi-arm polyethylene glycol-based microparticles with biscysteine peptide crosslinkers (CGPGG↓LAGGC) were obtained for intradermal drug delivery through inverse suspension photopolymerization. The average size of the spherical hydrated microparticles was ∼40 μm after crosslinking, making them attractive as a skin depot and suitable for intradermal injections, as they are readily dispensable through 27G needles. The effects of exposure to matrix metalloproteinase 9 (MMP-9) on the microparticles were evaluated by scanning electron microscopy and atomic force microscopy, demonstrating partial network destruction and decrease in elastic moduli.

Antibacterial Nanomaterials: Mechanisms, Impacts on Antimicrobial Resistance and Design Principles.

Antimicrobial resistance (AMR) is one of the biggest threats to the environment and health. AMR rapidly invalidates conventional antibiotics, and antimicrobial nanomaterials have been increasingly explored as alternatives. Interestingly, several antimicrobial nanomaterials show AMR-independent antimicrobial effects without detectable new resistance and have therefore been suggested to prevent AMR evolution.

Design and characterization of matrix metalloproteinase-responsive hydrogels for the treatment of inflammatory skin diseases.

Enzyme-responsive hydrogels, formed by step growth photopolymerization of biscysteine peptide linkers with alkene functionalized polyethylene glycol, provide interesting opportunities as biomaterials and drug delivery systems. In this study, we developed stimuli-responsive, specific, and cytocompatible hydrogels for delivery of anti-inflammatory drugs for the treatment of inflammatory skin diseases. We designed peptide linkers with optimized sensitivity towards matrix metalloproteinases, a family of proteolytic enzymes overexpressed in the extracellular matrix of the skin during inflammation.

Insights into the mechanisms of interaction between inhalable lipid-polymer hybrid nanoparticles and pulmonary surfactant.

Pulmonary delivery of small interfering RNA (siRNA) using nanoparticle-based delivery systems is promising for local treatment of respiratory diseases. We designed dry powder inhaler formulations of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) with aerosolization properties optimized for inhalation therapy. Interactions between LPNs and pulmonary surfactant (PS) determine the fate of inhaled LPNs, but interaction mechanisms are unknown.

Surface-Functionalized Polystyrene Nanoparticles Alter the Transmembrane Potential via Ion-Selective Pores Maintaining Global Bilayer Integrity.

Although nanoplastics have well-known toxic effects toward the environment and living organisms, their molecular toxicity mechanisms, including the nature of nanoparticle-cell membrane interactions, are still under investigation. Here, we employ dynamic light scattering, quartz crystal microbalance with dissipation monitoring, and electrophysiology to investigate the interaction between polystyrene nanoparticles (PS NPs) and phospholipid membranes. Our results show that PS NPs adsorb onto lipid bilayers creating soft inhomogeneous films that include disordered defects.

Mesoporous silica as a matrix for photocatalytic titanium dioxide nanoparticles: lipid membrane interactions.

In the present study, we investigate the combined interaction of mesoporous silica (SiO) and photocatalytic titanium dioxide (TiO) nanoparticles with lipid membranes, using neutron reflectometry (NR), cryo-transmission electron microscopy (cryo-TEM), fluorescence oxidation assays, dynamic light scattering (DLS), and ζ-potential measurements. Based on DLS, TiO nanoparticles were found to display strongly improved colloidal stability at physiological pH of skin (pH 5.4) after incorporation into either smooth or spiky ("virus-like") mesoporous silica nanoparticles at low pH, the latter demonstrated by cryo-TEM.

In Situ Transformation of Electrospun Nanofibers into Nanofiber-Reinforced Hydrogels.

Nanofiber-reinforced hydrogels have recently gained attention in biomedical engineering. Such three-dimensional scaffolds show the mechanical strength and toughness of fibers while benefiting from the cooling and absorbing properties of hydrogels as well as a large pore size, potentially aiding cell migration. While many of such systems are prepared by complicated processes where fibers are produced separately to later be embedded in a hydrogel, we here provide proof of concept for a one-step solution.

Zein-polycaprolactone core-shell nanofibers for wound healing.

In a previous study, we developed electrospun antimicrobial microfiber scaffolds for wound healing composed of a core of zein protein and a shell containing polyethylene oxide. While providing a promising platform for composite nanofiber design, the scaffolds showed low tensile strengths, insufficient water stability, as well as burst release of the antimicrobial drug tetracycline hydrochloride, properties which are not ideal for the use of the scaffolds as wound dressings. Therefore, the aim of the present study was to develop fibers with enhanced mechanical strength and water stability, also displaying sustained release of tetracycline hydrochloride.

Photocatalytic nanoparticles - From membrane interactions to antimicrobial and antiviral effects.

As a result of increasing resistance among pathogens against antibiotics and anti-viral therapeutics, nanomaterials are attracting current interest as antimicrobial agents. Such materials offer triggered functionalities to combat challenging infections, based on either direct membrane action, effects of released ions, thermal shock induced by either light or magnetic fields, or oxidative photocatalysis. In the present overview, we focus on photocatalytic antimicrobial effects, in which light exposure triggers generation of reactive oxygen species.

Effect of PEGylation on Host Defense Peptide Complexation with Bacterial Lipopolysaccharide.

Conjugation with poly(ethylene glycol) ("PEGylation") is a widely used approach for improving the therapeutic propensities of peptide and protein drugs through prolonging bloodstream circulation, reducing toxicity and immunogenicity, and improving proteolytic stability. In the present study, we investigate how PEGylation affects the interaction of host defense peptides (HDPs) with bacterial lipopolysaccharide (LPS) as well as HDP suppression of LPS-induced cell activation. In particular, we investigate the effects of PEGylation site for KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), a peptide displaying potent anti-inflammatory effects, primarily provided by its N-terminal part.

Composition effects on photooxidative membrane destabilization by TiO nanoparticles.

Membrane interactions and photooxidative membrane destabilization of titanium dioxide (TiO) nanoparticles were investigated, focusing on the effects of membrane composition, notably phospholipid headgroup charge and presence of cholesterol. For this, we employed a battery of state-of-the-art methods for studies of bilayers formed by zwitterionic palmitoyloleoylphosphatidylcholine (POPC) containing also polyunsaturated palmitoylarachidonoylphosphocholine (PAPC), as well as its mixtures with anionic palmitoyloleoylphosphatidylglycerol (POPG) and cholesterol. It was found that the TiO nanoparticles display close to zero charge at pH 7.