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Background We previously showed that cerium oxide (CeO 2 ), barium sulfate (BaSO 4 ) and zinc oxide (ZnO) nanoparticles (NPs) exhibited different lung toxicity and pulmonary clearance in rats. We hypothesize that these NPs acquire coronas with different protein compositions that may influence their clearance from the lungs. Methods CeO 2 , silica-coated CeO 2 , BaSO 4 , and ZnO NPs were incubated in rat lung lining fluid in vitro. Then, gel electrophoresis followed by quantitative mass spectrometry was used to characterize the adsorbed proteins stripped from these NPs. We also measured uptake of instilled NPs by alveolar macrophages (AMs) in rat lungs using electron microscopy. Finally, we tested whether coating of gold NPs with albumin would alter their lung clearance in rats. Results We found that the amounts of nine proteins in the coronas formed on the four NPs varied significantly. The amounts of albumin, transferrin and α-1 antitrypsin were greater in the coronas of BaSO 4 and ZnO than that of the two CeO 2 NPs. The uptake of BaSO 4 in AMs was less than CeO 2 and silica-coated CeO 2 NPs. No identifiable ZnO NPs were observed in AMs. Gold NPs coated with albumin or citrate instilled into the lungs of rats acquired the similar protein coronas and were cleared from the lungs to the same extent. Conclusions We show that different NPs variably adsorb proteins from the lung lining fluid. The amount of albumin in the NP corona varies as does NP uptake by AMs. However, albumin coating does not affect the translocation of gold NPs across the air-blood barrier. A more extensive database of corona composition of a diverse NP library will develop a platform to help predict the effects and biokinetics of inhaled NPs.

Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10 −8 –10 −6  M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10 −7 –10 −4  M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of magnitude lower concentrations. PEG and sucrose maintained immunogenicity in vivo for viruses stored for 10 days at 37 °C. To achieve rational design of viral-vaccine stabilizers, our approach is aided by simplified quantitative models based on a single rate-limiting step. Keeping viral vaccines cold from the manufacturers to patients is problematic and costly. Here, Krol and others show additives that can significantly improve at very low concentrations the storage of adenovirus type 5 at ambient and elevated temperature.

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnoses that severely limit therapeutic interventions. In this context, nanoparticle-mediated photothermal therapy (PTT) has emerged as a promising and minimally toxic modality for solid tumors. We synthesized gold nanoparticles (AuNPs) with three distinct morphologies—spheres, rods, and stars—and functionalized them with polyethylene glycol (AuNPs-PEG) or polyethylene glycol conjugated with 2-deoxy-D-glucose (AuNPs-Gluc). In vitro analyses using human (A549, H1299) and murine (LLC) lung carcinoma cell lines demonstrated that PEGylation significantly attenuated AuNP-associated cytotoxicity, while glucose functionalization further enhanced biocompatibility. Inductively coupled plasma mass spectrometry quantification confirmed superior cellular uptake of AuNPs-Gluc compared to AuNPs-PEG ( p  < 0.05). Subsequent irradiation with a 980 nm diode laser (1 W) induced robust thermal damage and apoptotic cell death selectively in cancer cells treated with AuNPs-Gluc, sparing non-tumoral cells. Among the morphologies tested, star-shaped AuNPs exhibited the highest photothermal efficiency. In vivo experiments further substantiated the therapeutic potential, as combined administration of AuNPs-Gluc and laser irradiation significantly suppressed tumor growth ( p  < 0.01). Collectively, these findings highlight the utility of glucose-functionalized AuNPs as effective vectors for targeted PTT in lung cancer, supporting their translational relevance for future clinical applications in advanced-stage disease.

The unique physicochemical properties of gold nanoparticles (GNPs) have made them versatile tools for biomedical applications, such as imaging, therapy, and drug delivery. The surface modification of GNPs with polymers or biomolecules can enhance their colloidal stability and facilitate internalization into cells. However, the efficient and biocompatible delivery to the central nervous system remains a major challenge, as many existing nanocarriers show poor capacity to cross the blood-brain barrier. We developed a method to coat GNPs with linear polyethyleneimine (GNP@PEI) through a chemical reduction bottom-up approach, in which linear PEI hydrochloride acts simultaneously as a reducing and stabilizing agent of colloidal dispersion. This strategy yielded monodisperse spherical GNP@PEI nanoparticles with an average diameter of 50 nm. The physicochemical profile, biocompatibility, and capacity for neural uptake of this potentially brain-targeted nanoplatform were then evaluated. GNP@PEI nanoparticles exhibited high biocompatibility in several primary neural cultures and cell lines, with cellular uptake showing clear cell-type-dependent differences. In vivo studies carried out in a murine model demonstrated that after the intranasal or intraperitoneal administrations of GNP@PEI nanoparticles, detectable levels of gold were found in several organs, including the brain. Collectively, these findings highlight the potential of GNP@PEI as a promising nanoplatform for brain-targeted delivery and for advancing the development of therapeutic strategies for neurological disorders.

Mechanochemistry is an emerging and reliable alternative to conventional solution (batch) synthesis of complex molecules under green and solvent-free conditions. In this regard, we report here on the conjugation of a dextran polysaccharide with a fluorescent probe, a phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the ball milling approach. The ball milling formation of boron esters between PBA BODIPY and dextran proved to be more efficient in terms of reaction time, amount of reactants, and labelling degree compared to the corresponding solution-based synthetic route. PBA-BODIPY dextran assembles into nanoparticles of around 200 nm by hydrophobic interactions. The resulting PBA-BODIPY dextran nanoparticles retain an apolar interior as proved by pyrene fluorescence, suitable for the encapsulation of hydrophobic drugs with high biocompatibility while remaining fluorescent.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. In ALS mice, neurodegeneration is associated with the proliferative restorative attempts of ependymal stem progenitor cells (epSPCs) that normally lie in a quiescent in the spinal cord. Thus, modulation of the proliferation of epSPCs may represent a potential strategy to counteract neurodegeneration. Recent studies demonstrated that FM19G11, a hypoxia-inducible factor modulator, induces epSPC self-renewal and proliferation. The aim of the study was to investigate whether FM19G11-loaded gold nanoparticles (NPs) can affect self-renewal and proliferation processes in epSPCs isolated from G93A-SOD1 mice at disease onset. We discovered elevated levels of SOX2, OCT4, AKT1, and AKT3, key genes associated with pluripotency, self-renewal, and proliferation, in G93A-SOD1 epSPCs at the transcriptional and protein levels after treatment with FM19G11-loaded NPs. We also observed an increase in the levels of the mitochondrial uncoupling protein (UCP) gene in treated cells. FM19G11-loaded NPs treatment also affected the expression of the cell cycle-related microRNA (miR)-19a, along with its target gene PTEN, in G93A-SOD1 epSPCs. Overall our findings establish the significant impact of FM19G11-loaded NPs on the cellular pathways involved in self-renewal and proliferation in G93A-SOD1 epSPCs, thus providing an impetus to the design of novel tailored approaches to delay ALS disease progression.

The aim of this research was to study TiO 2 nanocoatings formation and to investigate their self-cleaning effects when applied on cellulose materials. Two different approaches for achieving nanocoatings were used. First, coatings were generated in situ through an acid and alkaline catalyzed sol-gel process with or without added water. Another type of coatings was prepared starting from commercial TiO 2 P25 powder. In order to acquire homogeneous coatings from TiO 2 P25 nanoparticles with uniform nanoparticles size distribution, pH of aqueous TiO 2 P25 dispersions was varied. The dispersion preparation conditions were studied by dynamic light scattering (DLS) and zeta potential ( ζ -potential) analysis. The resulting TiO 2 nanocoatings were analyzed in terms of their surface morphology using scanning electron microscopy (SEM). Nanocoatings obtained from pure aqueous dispersions of TiO 2 P25 nanoparticles were inhomogeneous with huge agglomerates; however by changing the pH of dispersion and consequently changing the surface charge of TiO 2 P25 nanoparticles as well, more homogeneous nanocoatings with uniform TiO 2 nanoparticles distribution were prepared. Significant differences between solgel derived coatings were observed. Sol-gel process without added water yielded more homogeneous coatings than sol-gel process with addition of water. Completely different surface morphologies were obtained using alkaline or acid catalyst. Acid catalyzed sol-gel process yielded nanocoatings with long, extended, thin structures; contrary, under alkaline conditions particles grow in size with decrease in number. Fourier transform infrared (FTIR) spectroscopy was used to study the coatings’ microstructure. Furthermore the formation of mono-disperse nanoparticles on the fiber surface resulted in enhanced photocatalytic activity. Degradation of colored stain applied on TiO 2 -treated samples was investigated by colorimetric measurements. Photocatalytic activity of nanocoatings prepared via acid catalyzed sol-gel process without water addition was comparable to that of nanocoatings derived from aqueous dispersions of commercial TiO 2 P25 nanoparticles.

Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism. These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

Recent work has demonstrated that charged gold nanoparticles (AuNPs) protected by an amphiphilic organic monolayer can spontaneously insert into the core of lipid bilayers to minimize the exposure of hydrophobic surface area to water. However, the kinetic pathway to reach the thermodynamically stable transmembrane configuration is unknown. Here, we use unbiased atomistic simulations to show the pathway by which AuNPs spontaneously insert into bilayers and confirm the results experimentally on supported lipid bilayers. The critical step during this process is hydrophobic–hydrophobic contact between the core of the bilayer and the monolayer of the AuNP that requires the stochastic protrusion of an aliphatic lipid tail into solution. This last phenomenon is enhanced in the presence of high bilayer curvature and closely resembles the putative pre-stalk transition state for vesicle fusion. To the best of our knowledge, this work provides the first demonstration of vesicle fusion-like behaviour in an amphiphilic nanoparticle system. Gold nanoparticles coated with amphiphilic ligands can spontaneously insert into lipid bilayers, reducing hydrophobic interactions. Here, the authors show the key step in this process is similar to vesicle fusion: lipid tails from the bilayer protrude into water before encountering the nanoparticle.

The deposition of amyloid-β (Aβ) plaques in the brain is a significant pathological signature of Alzheimer’s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop Aβ aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), which is derived from the receptor binding sequence of apolipoprotein E, is effectively able to inhibit Aβ aggregation and to promote fibril disaggregation. Taking advantage of Atomic Force Microscopy (AFM) imaging and fluorescence techniques, we investigate if the clustering of mApoE on gold nanoparticles (AuNP) surface may affect its performance in controlling Aβ aggregation/disaggregation processes. The results showed that the ability of free mApoE to destroy preformed Aβ fibrils or to hinder the Aβ aggregation process is preserved after its clustering on AuNP. This allows the possibility to design multifunctional drug delivery systems with clustering of anti-amyloidogenic molecules on any NP surface without affecting their performance in controlling Aβ aggregation processes.