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Deposition of complement factors (opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical role in C3 opsonization of SPIO nanoworms and a range of clinically approved nanopharmaceuticals. The dependency of C3 opsonization on immunoglobulin binding is almost universal and is observed regardless of the complement activation pathway. Only a few surface-bound immunoglobulin molecules are needed to trigger complement activation and opsonization. Although the total amount of plasma proteins adsorbed on nanoparticles does not determine C3 deposition efficiency, the biomolecule corona per se enhances immunoglobulin binding to all nanoparticle types. We therefore show that natural antibodies represent a link between biomolecule corona and C3 opsonization, and may determine individual complement responses to nanomedicines.Immunoglobulins mediate deposition of the third complement protein (C3) on the biomolecule corona of nanoparticles, promoting complement activation.

The polymeric shell surrounding gold nanoparticles may degrade when injected into rats, suggesting that even highly stable colloidal nanoparticles are susceptible to physicochemical changes in vivo . Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties 1 may change upon internalization by cells 2 , 3 . While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats. We synthesized monodisperse radioactively labelled gold nanoparticles ( 198 Au) 4 and engineered an 111 In-labelled polymer shell around them 5 . Upon intravenous injection into rats, quantitative biodistribution analyses performed independently for 198 Au and 111 In showed partial removal of the polymer shell in vivo . While 198 Au accumulates mostly in the liver, part of the 111 In shows a non-particulate biodistribution similar to intravenous injection of chelated 111 In. Further in vitro studies suggest that degradation of the polymer shell is caused by proteolytic enzymes in the liver. Our results show that even nanoparticles with high colloidal stability can change their physicochemical properties in vivo .

There is considerable interest in developing anti-glioma nanoplatforms. They make the all-in-one combination of therapies possible. Here we show how the selective Glioblastoma multiforme (GBM) cell killing of the here-established nanoplatforms increased after each coating and how the here-established vibration-inducing Alternating magnetic field (AMF) decreased the treatment time from 72 h to 30 s. Thanks to their magnetite core, these nanoplatforms can be guided to the tumor's specific site by a Fixed magnetic field, they bypass the Blood–Brain Barrier (BBB) and accumulate at the tumor site thanks to the RVG29 bonding to the G-protein on the ion-gated channel receptor known as the nicotinic acetylcholine receptor (nAchR), which expresses on BBB cells and overexpresses on GBM cells, and thanks to the positive charge gained by both chitosan and RVG29's peptide. Both ZIF-8 and its mediate adherence, Chitosan increases the drug loading capacity that stimuli response to the tumor's acidic environment. The Zn 2+ ions generated from ZIF-8 sustained degradation in such an environment kill the GBM cells. Dynamic Light Scattering (DLS) evaluated these nanoplatform's mean size 155 nm indicating their almost optimum size for brain applications. Based on their elements' intrinsic properties, these nanoplatforms can enhance and combine other adjuvant therapies.

We investigated whether Aluminum (Al) doping tunes band gap energy level as well as selective cytotoxicity of ZnO nanoparticles in human breast cancer cells (MCF-7). Pure and Al-doped ZnO nanoparticles were prepared by a simple sol-gel method. Characterization study confirmed the formation of single phase of Al x Zn 1-x O nanocrystals with the size range of 33–55 nm. Al-doping increased the band gap energy of ZnO nanoparticles (from 3.51 eV for pure to 3.87 eV for Al-doped ZnO). Al-doping also enhanced the cytotoxicity and oxidative stress response of ZnO nanoparticles in MCF-7 cells. The IC50 for undoped ZnO nanoparticles was 44 μg/ml while for the Al-doped ZnO counterparts was 31 μg/ml. Up-regulation of apoptotic genes (e.g. p53, bax/bcl2 ratio, caspase-3 & caspase-9) along with loss of mitochondrial membrane potential suggested that Al-doped ZnO nanoparticles induced apoptosis in MCF-7 cells through mitochondrial pathway. Importantly, Al-doping did not change the benign nature of ZnO nanoparticles towards normal cells suggesting that Al-doping improves the selective cytotoxicity of ZnO nanoparticles toward MCF-7 cells without affecting the normal cells. Our results indicated a novel approach through which the inherent selective cytotoxicity of ZnO nanoparticles against cancer cells can be further improved.

While the global healthcare system is slowly recovering from the COVID-19 pandemic, new multi-drug-resistant pathogens are emerging as the next threat. To tackle these challenges there is a need for safe and sustainable antiviral and antibacterial functionalized materials. Here we develop an 'easy-to-apply' procedure for the surface functionalization of textiles, rendering them antiviral and antibacterial and assessing the performance of these textiles. A metal-free quaternary ammonium-based coating was applied homogeneously and non-covalently to hospital curtains. Abrasion, durability testing, and aging resulted in little change in the performance of the treated textile. Additionally, qualitative and quantitative antibacterial assays on Staphylococcus aureus , Pseudomonas aeruginosa, and Acinetobacter baumanii revealed excellent antibacterial activity with a CFU reduction of 98–100% within only 4 h of exposure. The treated curtain was aged 6 months before testing. Similarly, the antiviral activity tested according to ISO-18184 with murine hepatitis virus (MHV) showed > 99% viral reduction with the functionalized curtain. Also, the released active compounds of the coating 24 ± 5 µg mL −1 revealed no acute in vitro skin toxicity (IC 50 : 95 µg mL −1 ) and skin sensitization. This study emphasizes the potential of safe and sustainable metal-free textile coatings for the rapid antiviral and antibacterial functionalization of textiles.

Lead exposure can cause substantial organ damage. Enteral lead absorption may be reduced by concomitant intake of clinoptilolite tuff, a zeolite from natural sources. This study aimed to assess the effect of purified clinoptilolite tuff (G-PUR) on enteral lead uptake in adults using stable lead isotope 204 Pb as a tracer. In this randomized, placebo-controlled, double-blind, parallel-group study, 42 healthy participants were randomized to receive oral G-PUR 2.0 g, 2 * 2.0 g, or placebo, together with 2.5 µg of 204 Pb in water. The enrichment of 204 Pb caused by the tracer in blood and urine was measured by mass spectrometry. G-PUR was well tolerated. The mean maximum 204 Pb enrichment of 0.505% of total blood lead was significantly higher (p < 0.0001) in the placebo group compared to G-PUR 2.0 g (0.073%) or G-PUR 2 * 2.0 g (0.057%) group. Normalized 204 Pb AUC 0-192 was 86.5, 11.9, and 8.5% * h without and with G-PUR 2.0 g, and G-PUR 2 * 2.0 g, respectively (p < 0.0001 vs. placebo). This smaller 204 Pb exposure was paralleled by a reduced urinary excretion in subjects receiving G-PUR. Concomitant oral intake of purified clinoptilolite tuff reduced enteral uptake of 204 Pb in healthy humans by approximately 90%. The reduced bioavailability is demonstrable by a decrease of 204 Pb tracer enrichment in blood and urine. Trial registration : clinicaltrials.gov identifier: NCT04138693, registered 24/10/2019.

Magnetic iron-oxide nanoparticles in the form of magnetite (Fe 3 O 4 ) are present in the human brain. They have been hypothesized to biomineralize in situ, as a result of dysfunctional iron homeostasis related to Alzheimer’s disease, or to enter the brain as airborne pollution particles. Regardless of their origin, magnetic iron-oxides pose a potential hazard to human health due to their high redox activity and surface charge. Here we report measurements on four post-mortem human brainstems, with one brainstem showing approximately 100 times higher magnetite concentrations than the other cases. This brainstem came from a subject with alcohol-associated liver disease (ALD) that manifested in liver cirrhosis and massive hepatic iron overload. Laser ablation – inductively coupled plasma – mass spectrometry showed the highest levels of trace metals (iron, copper and manganese) in the ALD brainstem. It is well established that a dysfunctional liver can result in the accumulation of trace metals in the brain. Our data indicate a similar pathway for magnetite particles, yet liver pathology has not been linked to magnetite occurrence in the brain so far. It may prove to be a crucial factor in understanding the high variation of magnetite concentrations found in human brains.

Nanoparticle exposure in pregnancy may result in placental damage and fetotoxicity; however, the factors that determine fetal nanoparticle exposure are unclear. Here we have assessed the effect of gestational age and nanoparticle composition on fetal accumulation of maternally-administered nanomaterials in mice. We determined the placental and fetal uptake of 13 nm gold nanoparticles with different surface modifications (ferritin, PEG and citrate) following intravenous administration at E5.5-15.5. We showed that prior to E11.5, all tested nanoparticles could be visualized and detected in fetal tissues in significant amounts; however, fetal gold levels declined dramatically post-E11.5. In contrast, Au-nanoparticle accumulation in the extraembryonic tissues (EET) increased 6–15 fold with gestational age. Fetal and EET accumulation of ferritin- and PEG-modified nanoparticles was considerably greater than citrate-capped nanoparticles. No signs of toxicity were observed. Fetal exposure to nanoparticles in murine pregnancy is, therefore, influenced by both stage of embryonic/placental maturation and nanoparticle surface composition.

Melamine, which induces proximal tubular (PT) cell damage has a greater nephrotoxic effect when combined with cyanuric and uric acids; however, it is unknown whether such effect can stimulate calcium phosphate (CaP)/calcium oxalate (CaOx) stone formation. Here, we show that melamine acts as an inducer of CaP, CaOx and CaP + CaOx (mixed) crystal formations in a time and concentration-dependent manner by stabilizing those crystals and further co-aggregating with melamine. To explore the physiological relevance of such melamine-augmented calcium crystal formation, we used 2-dimensional (2D) and 3D microfluidic (MF) device, embedded with PT cells, which also resembled the effect of melamine-stimulated CaP, CaOx and mixed crystal formation. Significantly, addition of preformed CaP and/or CaOx crystal in the presence of melamine, further potentiated those crystal formations in 3D MFs, which helped the growth and aggregation of mixed crystals. Our data show that the mechanism of such predisposition of stone formation could be largely due to co-crystallization between melamine and CaP/CaOx and pronounced effect on induction of stone-forming pathway activation in 3D MF. Taken together, melamine-induced CaP and/or CaOx crystal formation ex-vivo will help us in understanding the larger role of melamine as an environmental toxicant in producing the pathology in similar cellular microenvironments.

A single dose of carbon nanotubes enhances breast cancer metastasis in mouse models.