Complex Structures Made Simple - Continuous Flow Production of Core Cross-Linked Polymeric Micelles for Paclitaxel Pro-Drug-Delivery.

Translating innovative nanomaterials to medical products requires efficient manufacturing techniques that enable large-scale high-throughput synthesis with high reproducibility. Drug carriers in medicine embrace a complex subset of tasks calling for multifunctionality. Here, the synthesisof pro-drug-loaded core cross-linked polymeric micelles (CCPMs) in a continuous flow processis reported, which combines the commonly separated steps of micelle formation, core cross-linking, functionalization, and purification into a single process.

Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure.

Background: Heart failure (HF) coincides with cardiomyocyte telomere shortening. Arterial hypertension is the most prominent risk factor for HF. Both HF and arterial hypertension are associated with dysregulation of the neurohormonal axis.

Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance.

Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy ( = 0.

TNF-α-Inhibition Improves the Biocompatibility of Porous Polyethylene Implants In Vivo.

Background: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor α (TNFα) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo.

Boosting nanotoxicity to combat multidrug-resistant bacteria in pathophysiological environments.

Nanomaterials are promising novel antibiotics, but often ineffective. We found that nanomaterial-bacteria complex formation occurred with various nanomaterials. The bactericidal activity of NMs strongly depends on their physical binding to (multidrug-resistant) bacteria.

Mechanisms of nanotoxicity - biomolecule coronas protect pathological fungi against nanoparticle-based eradication.

Whereas nanotoxicity is intensely studied in mammalian systems, our knowledge of desired or unwanted nano-based effects for microbes is still limited. Fungal infections are global socio-economic health and agricultural problems, and current chemical antifungals may induce adverse side-effects in humans and ecosystems. Thus, nanoparticles are discussed as potential novel and sustainable antifungals via the desired nanotoxicity but often fail in practical applications.

Investigating the Vascular Toxicity Outcomes of the Irreversible Proteasome Inhibitor Carfilzomib.

Background: Carfilzomib's (Cfz) adverse events in myeloma patients include cardiovascular toxicity. Since carfilzomib's vascular effects are elusive, we investigated the vascular outcomes of carfilzomib and metformin (Met) coadministration.

Methods: Mice received: (i) saline; (ii) Cfz; (iii) Met; (iv) Cfz+Met for two consecutive (acute) or six alternate days (subacute protocol).

The other side of the corona: nanoparticles inhibit the protease taspase1 in a size-dependent manner.

When nanoparticles enter a physiological environment, they rapidly adsorb biomolecules, in particular cellular proteins. This biological coating, the so-called nanoparticle protein corona, undoubtedly affects the biological identity and potential cytotoxicity of the nanomaterial. To elucidate a possible impact on the adsorbed biomolecules, we focused on an important group of players in cellular homeostasis, namely proteolytic enzymes.

Nano Meets Micro-Translational Nanotechnology in Medicine: Nano-Based Applications for Early Tumor Detection and Therapy.

Nanomaterials have great potential for the prevention and treatment of cancer. Circulating tumor cells (CTCs) are cancer cells of solid tumor origin entering the peripheral blood after detachment from a primary tumor. The occurrence and circulation of CTCs are accepted as a prerequisite for the formation of metastases, which is the major cause of cancer-associated deaths.

Early Alterations of Endothelial Nitric Oxide Synthase Expression Patterns in the Guinea Pig Cochlea After Noise Exposure.

Constitutively expressed endothelial nitric oxide synthase (eNOS) is supposed to play a role in noise-induced nitric oxide (NO)-production. It is commonly known that intense noise exposure results in inducible NOS (iNOS) expression and increased NO-production, but knowledge about a contribution of the eNOS isoform is still lacking. Effects of noise exposure on eNOS immunolabeling were determined in male guinea pigs (=24).

Resistance to Nano-Based Antifungals Is Mediated by Biomolecule Coronas.

Fungal infections are a growing global health and agricultural threat, and current chemical antifungals may induce various side-effects. Thus, nanoparticles are investigated as potential novel antifungals. We report that nanoparticles' antifungal activity strongly depends on their binding to fungal spores, focusing on the clinically important fungal pathogen Aspergillus fumigatus as well as common plant pathogens, such as Botrytis cinerea.

Biomolecule-corona formation confers resistance of bacteria to nanoparticle-induced killing: Implications for the design of improved nanoantibiotics.

Multidrug-resistant bacterial infections are a global health threat. Nanoparticles are thus investigated as novel antibacterial agents for clinical practice, including wound dressings and implants. We report that nanoparticles' bactericidal activity strongly depends on their physical binding to pathogens, including multidrug-resistant primary clinical isolates, such as Staphylococcus aureus, Klebsiella pneumoniae or Enterococcus faecalis.

Small Meets Smaller: Effects of Nanomaterials on Microbial Biology, Pathology, and Ecology.

As functionalities and levels of complexity in nanomaterials have increased, unprecedented control over microbes has been enabled, as well. In addition to being pathogens and relevant to the human microbiome, microbes are key players for sustainable biotechnology. To overcome current constraints, mechanistic understanding of nanomaterials' physicochemical characteristics and parameters at the nano-bio interface affecting nanomaterial-microbe crosstalk is required.

Nanoparticle decoration impacts airborne fungal pathobiology.

Airborne fungal pathogens, predominantly , can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization.

Nanosized food additives impact beneficial and pathogenic bacteria in the human gut: a simulated gastrointestinal study.

Nanotechnology provides the food industry with new ways to modulate various aspects of food. Hence, engineered nanoparticles (NPs) are increasingly added to food and beverage products as functional ingredients. However, the impact of engineered as well as naturally occurring NPs on both commensal and pathogenic microorganisms within the gastrointestinal tract (GI) is not fully understood.