Fighting viruses with materials science: Prospects for antivirus surfaces,drug delivery systems and artificial intelligence

ObjectiveViruses on environmental surfaces, in saliva and other body fluids represent risk of contamination for general population and healthcare professionals. The development of vaccines and medicines is costly and time consuming. Thus, the development of novel materials and technologies to decrease viral availability, viability, infectivity, and to improve therapeutic outcomes can positively impact the prevention and treatment of viral diseases.MethodsHerein, we discuss (a) interaction mechanisms between viruses and materials, (b) novel strategies to develop materials with antiviral properties and oral antiviral delivery systems, and (c) the potential of artificial intelligence to design and optimize preventive measures and therapeutic regimen.ResultsThe mechanisms of viral adsorption on surfaces are well characterized but no major breakthrough has become clinically available. Materials with fine-tuned physical and chemical properties have the potential to compromise viral availability and stability. Emerging strategies using oral antiviral delivery systems and artificial intelligence can decrease infectivity and improve antiviral therapies.SignificanceEmerging viral infections are concerning due to risk of mortality, as well as psychological and economic impacts. Materials science emerges for the development of novel materials and technologies to diminish viral availability, infectivity, and to enable enhanced preventive and therapeutic strategies, for the safety and well-being of humankind.     

Applicability of rat precision-cut lung slices in evaluating nanomaterial cytotoxicity,apoptosis, oxidative stress,and inflammation

The applicability of rat precision-cut lung slices (PCLuS) in detecting nanomaterial (NM) toxicity to the respiratory tract was investigated evaluating sixteen OECD reference NMs (TiO₂, ZnO, CeO₂, SiO₂, Ag, multi-walled carbon nanotubes (MWCNTs)). Upon 24-hour test substance exposure, the PCLuS system was able to detect early events of NM toxicity: total protein, reduction in mitochondrial activity, caspase-3/-7 activation, glutathione depletion/increase, cytokine induction, and histopathological evaluation. Ion shedding NMS (ZnO and Ag) induced severe tissue destruction detected by the loss of total protein. Two anatase TiO₂ NMs, CeO₂ NMs, and two MWCNT caused significant (determined by trend analysis) cytotoxicity in the WST-1 assay. At non-cytotoxic concentrations, different TiO₂ NMs and one MWCNT increased GSH levels, presumably a defense response to reactive oxygen species, and these substances further induced a variety of cytokines. One of the SiO₂ NMs increased caspase-3/-7 activities at non-cytotoxic levels, and one rutile TiO₂ only induced cytokines. Investigating these effects is, however, not sufficient to predict apical effects found in vivo. Reproducibility of test substance measurements was not fully satisfactory, especially in the GSH and cytokine assays. Effects were frequently observed in negative controls pointing to tissue slice vulnerability even though prepared and handled with utmost care. Comparisons of the effects observed in the PCLuS to in vivo effects reveal some concordances for the metal oxide NMs, but less so for the MWCNT. The highest effective dosages, however, exceeded those reported for rat short-term inhalation studies. To become applicable for NM testing, the PCLuS system requires test protocol optimization.     

Approaches to the safety assessment of engineered nanomaterials (ENM) in food

A systematic, tiered approach to assess the safety of engineered nanomaterials (ENMs) in foods is presented. The ENM is first compared to its non-nano form counterpart to determine if ENM-specific assessment is required. Of highest concern from a toxicological perspective are ENMs which have potential for systemic translocation, are insoluble or only partially soluble over time or are particulate and bio-persistent. Where ENM-specific assessment is triggered, Tier 1 screening considers the potential for translocation across biological barriers, cytotoxicity, generation of reactive oxygen species, inflammatory response, genotoxicity and general toxicity. In silico and in vitro studies, together with a sub-acute repeat-dose rodent study, could be considered for this phase. Tier 2 hazard characterisation is based on a sentinel 90-day rodent study with an extended range of endpoints, additional parameters being investigated case-by-case. Physicochemical characterisation should be performed in a range of food and biological matrices. A default assumption of 100% bioavailability of the ENM provides a ‘worst case’ exposure scenario, which could be refined as additional data become available. The safety testing strategy is considered applicable to variations in ENM size within the nanoscale and to new generations of ENM.     

A current overview of health effect research on nanoparticles

Nanotoxicology and nano-risk have been attracting increasing attention of toxicologists and regulatory scientists as the production of nanomaterials increases worldwide (Oberdorster et al. in Environ Health Perspect 113:823–839, 2005). In general, nanotoxicology is associated with manufactured nanomaterials. In atmospheric science and environmental health science, however, very small particles that exist transiently at high count concentrations near road intersections and roadsides are called environmental nanoparticles, and most of these have originated from automobiles. Accordingly there are two types of nanoparticle in toxicology and health science—environmental nanoparticles and manufactured or engineered nanoparticles. In this minireview I would like to address the following issues: (1) What is a nanoparticle? (2) Why is the nanoparticle currently a significant health issue? (3) How has “testing manufactured nanoparticles” been discussed worldwide? (4) What problems have scientists encountered in assessing the health hazard of nanoparticles? and (5) What research is required in the future in nanotoxicology?     

Biological response and morphological assessment of individually dispersed multi-wall carbon nanotubes in the lung after intratracheal instillation in rats

Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after a single intratracheal instillation in rats. The diameter and median length of the MWCNTs used in this study were approximately 60 nm and 1.5 μm, respectively. Groups of male Sprague–Dawley rats were intratracheally instilled with 0.04, 0.2, or 1 mg/kg of the individually dispersed MWCNT suspension. After instillation, the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers, and the lung, liver, kidney, spleen, and cerebrum were histopathologically evaluated at 3-day, 1-week, 1-month, 3-month, and 6-month post-exposure. Transient pulmonary inflammatory responses were observed only in the lungs of the group of rats exposed to 1 mg/kg of MWCNTs. Morphology of the instilled MWCNTs in the lungs of rats was assessed using light microscopy and transmission electron microscopy (TEM). Light microscopy examination revealed that MWCNTs deposited in the lungs of the rats were typically phagocytosed by the alveolar macrophages and these macrophages were consequently accumulated in the alveoli until 6-month post-exposure. The 400 TEM images obtained showed that all MWCNTs were located in the alveolar macrophages or macrophages in the interstitial tissues, and MWCNTs were not located in the cells of the interstitial tissues. There was no evidence of chronic inflammation, such as angiogenesis or fibrosis, induced by MWCNT instillation. These results suggest that MWCNTs were being processed and cleared by alveolar macrophages.     

Oxidative stress studies of six TiO2 and two CeO2 nanomaterials: Immuno-spin trapping results with DNA

Abstract

Six TiO₂ and two CeO₂ nanomaterials with dry sizes ranging from 6–410 nm were tested for their ability to cause DNA centered free radicals in vitro in the concentration range of 10–3,000 ug/ml. All eight of the nanomaterials significantly increased the adduction of the spin trap agent 5,5-dimethyl-1-pyroline N-oxide (DMPO) to DNA as measured by the experimental technique of immuno-spin trapping. The eight nanomaterials differed considerably in their potency, slope, and active concentration. The largest increase in DNA nitrone adducts was caused by a TiO₂ nanomaterial (25 nm, anatase) from Alfa Aesar. Some nanomaterials that increased the amount of DNA nitrone adducts at the lowest exposure concentrations (100 ug/ml) were Degussa TiO₂ (31 nm), Alfa Aesar TiO₂ (25 nm, anatase) and Nanoamor CeO₂ (8 nm, cerianite). At exposure concentrations of 10 or 30 ug/ml, no nanomaterials showed significant in vitro formation of DNA nitrone adducts.     

Fish cell lines as a tool for the ecotoxicity assessment and ranking of engineered nanomaterials

Risk assessment of engineered nanomaterials (ENMs) is being hindered by the sheer production volume of these materials. In this regard, the grouping and ranking of ENMs appears as a promising strategy. Here we sought to evaluate the usefulness of in vitro systems based on fish cell lines for ranking a set of ENMs on the basis of their cytotoxicity. We used the topminnow (Poeciliopsis lucida) liver cell line (PLHC-1) and the rainbow trout (Oncorhynchus mykiss) fibroblast-like gonadal cell line (RTG-2). ENMs were obtained from the EU Joint Research Centre repository. The size frequency distribution of ENM suspensions in cell culture media was characterized. Cytotoxicity was evaluated after 24 h of exposure. PLHC-1 cells exhibited higher sensitivity to the ENMs than RTG-2 cells. ZnO-NM was found to exert toxicity mainly by altering lysosome function and metabolic activity, while multi-walled carbon nanotubes (MWCNTs) caused plasma membrane disruption at high concentrations. The hazard ranking for toxicity (ZnO-NM > MWCNT ≥ CeO₂-NM = SiO₂-NM) was inversely related to the ranking in size detected in culture medium. Our findings reveal the suitability of fish cell lines for establishing hazard rankings of ENMs in the framework of integrated approaches to testing and assessment.     

Case studies putting the decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) into practice

Case studies covering carbonaceous nanomaterials, metal oxide and metal sulphate nanomaterials, amorphous silica and organic pigments were performed to assess the Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). The usefulness of the DF4nanoGrouping for nanomaterial hazard assessment was confirmed. In two tiers that rely exclusively on non-animal test methods followed by a third tier, if necessary, in which data from rat short-term inhalation studies are evaluated, nanomaterials are assigned to one of four main groups (MGs). The DF4nanoGrouping proved efficient in sorting out nanomaterials that could undergo hazard assessment without further testing. These are soluble nanomaterials (MG1) whose further hazard assessment should rely on read-across to the dissolved materials, high aspect-ratio nanomaterials (MG2) which could be assessed according to their potential fibre toxicity and passive nanomaterials (MG3) that only elicit effects under pulmonary overload conditions. Thereby, the DF4nanoGrouping allows identifying active nanomaterials (MG4) that merit in-depth investigations, and it provides a solid rationale for their sub-grouping to specify the further information needs. Finally, the evaluated case study materials may be used as source nanomaterials in future read-across applications. Overall, the DF4nanoGrouping is a hazard assessment strategy that strictly uses animals as a last resort.     

皮下种植纳米根管封闭材料的组织学反应

目的观察纳米根管封闭材料的组织相容性。方法将3个填有不同实验材料的硅胶管和1个空硅胶管（作为空白对照）置于SD大鼠皮下组织内,分别于2周和12周后处死动物,取出植入块,镜下观察组织学反应,并根据炎症分级情况评价组织相容性。结果2周时,各组的炎症分级情况有明显差别（P〈0．05）,N—ZO组和NHA组的炎症分级情况优于ZOE组（对照组）;12周时,N—ZO组和NHA组的炎症分级情况优于ZOE组（对照组）（P〈0．01）。结论纳米氧化锌糊剂和纳米羟磷灰石糊剂具有良好的组织相容性,从这个角度讲可以作为根管封闭剂用于根管充填。     

纳米根管充填材料根尖封闭能力的实验研究

目的 观察纳米材料根充后根尖微渗漏请况，评价其根尖封闭能力。方法 30颗离体单根管牙牙根，随机分为三组，每组10个，预备完成的根管用牙胶尖和一种根管糊荆、采用侧方加压法进行充填。根据染料在牙根中的渗入深度，评价根尖微渗漏情况。结果 三种材料的根尖微渗漏有显著差异（P〈0．01）；n-ZO组的根尖微渗漏最小，n-HA组次之，ZOE组最大。结论 纳米氧化锌糊剂和纳米羟磷灰石糊剂具有良好的根尖封闭性，可以作为根管封闭剞用于根管充填。