Toxicity of nanomaterials; an undermined issue

Nanomaterials are employed in extensive variety of commercial products such as electronic components, cosmetics, food, sports equipment, biomedical applications, and medicine. With the increasing utilization of engineered nanomaterials, the potential exposure of human to nanoparticles is rapidly increasing. Nowadays when new nanomaterials with new applications are introduced, mostly good and positive effects are mentioned whereas possible hazards arising from nanosize of the compounds are undermined. Toxicology studies of nanomaterials demonstrate some adverse effects in some human organs such as central nerve system, immune system, and lung. There is lack of complete information about human toxicity and environmental waste of nanomaterials. We aimed to highlight current toxicological concerns of potentially useful nanomaterials which are now used in pharmaceutical and biomedical sciences.     

Polymeric membrane materials for artificial organs

Many polymeric materials have already been used in the field of artificial organs. However, the materials used in artificial organs are not necessarily created with the best material selectivity and materials design; therefore, the development of synthesized polymeric membrane materials for artificial organs based on well-defined designs is required. The approaches to the development of biocompatible polymeric materials fall into three categories: (1) control of physicochemical characteristics on material surfaces, (2) modification of material surfaces using biomolecules, and (3) construction of biomimetic membrane surfaces. This review will describe current issues regarding polymeric membrane materials for use in artificial organs. This is an updated version of an article originally published in The Japanese Journal of Artificial Organs 2006;35:189–192     

纳米材料与化妆品

纳米技术是21世纪最有前途的技术之一.纳米材料由于具有不同于普通材料的物理、化学和生物特性,正越来越多地开发用于多个领域.赋予纳米材料新特性的主要因素是相对表面积的增大和量子效应.用于化妆品的纳米材料有纳米ZnO和TiO2、富勒烯、纳米泡囊、纳米乳剂和纳米微粒等.纳米材料用于化妆品展现明显的优点,其安全性也受到关注.     

Proanthocyanidin-functionalized hydroxyapatite nanoparticles as dentin biomodifier

ObjectiveThis study evaluated the potential combined effects of nanohydroxyapatite and proanthocyanidin on the remineralization and collagen stabilization of demineralized dentin.MethodsSeventy-five coronal dentin beams (6 × 1 × 1 mm³) were randomly allocated into five experimental groups (n = 15): Sound (no treatment), Control (pH-cycling), nHAp (nanohydroxyapatite), nHAp_PA (Proanthocyanidin-functionalized nanohydroxyapatite), and PA (proanthocyanidin) treatments. The sound group (negative control) were immersed in distilled water over the experimental period. The remaining groups were submitted to a pH-cycling process for 14 days. Following the de-re mineralization process, specimens corresponding to the control group (positive control) were immersed in distilled water whereas the test groups were immersed in 1 mL of respective solution treatment (nHAp, nHAp_PA, or PA) for 1 min. The dentin samples were analyzed to determine their chemical composition (ATR-FTIR and Thermogravimetric) and mineralogical (XRD) characteristics as well as their mechanical response, obtained by three-point bending test.ResultsHigher phosphate content (v₄ PO₄: ATR-FTIR) and amount of mineral (XRD) was observed in the nHAp_PA group. Furthermore, a larger induction of collagen cross-links (ATR-FTIR) and %Organic Matter (TGA) would indicate the PA incorporation and the achievement of dentin matrix stability. These effects on dentin properties were related to increasing flexural strength (MPa), demonstrating that 15% w/v nHAp_PA treatment improved the mechanical properties of the samples.SignificancenHAp_PA shows significant potential for promoting remineralization while improving collagen stability into demineralized dentin in a clinically feasible period of 1 min.     

Inhibition of inhaled halloysite nanotube toxicity by trehalose through enhanced autophagic clearance of p62

Nanomaterials are widely used in an ever-increasing number of consumer and industrial products. It is therefore essential that the toxic effects of nanomaterials are understood in order to improve product safety. Here we evaluate the toxicity of inhaled halloysite nanotubes (HNTs) by applying a purpose designed inhalation exposure system and succeed in suppressing HNTs toxicity using trehalose. By assessing apoptosis, oxidative stress, inflammatory response, and autophagy, it is found that HNTs can cause sub-chronic toxicity in mice. Further investigations indicate that HNTs induce autophagy blockade that results in the accumulation of sequestosome-1 (p62), which is responsible for the excessive apoptosis, inflammatory response and oxidative stress. We found that p62 can be eliminated by trehalose and the application of trehalose in vitro and in vivo successfully inhibits toxicity by accelerating the clearance of p62. Trehalose shows great potential for reducing nanoparticle toxicity.     

Methodological considerations when conducting in vitro,air–liquid interface exposures to engineered nanoparticle aerosols

Little consistency exists in the methodology for toxicological testing of aerosolized nanoparticles used in in vitro, air-interfaced culture (AIC) exposure systems for engineered nanoparticles (ENPs) risk-assessment, preventing inter-laboratory comparisons to identify dose thresholds for adverse effects. These inconsistencies result from heterogeneity in particle types, exposure durations, exposure systems, and dose metrics reported. We screened 10,241 studies in the literature for toxicological assessment of ENPs, resulting in 110 publications included after meeting eligibility criteria. In this review, we critically analyzed methodology within these studies to answer whether: (1) the administered dose or the deposited dose correlated better with biological response, (2) a difference existed between various AIC exposure systems when depositing the same dose, (3) consistent results were generated for nanomaterials with similar physico-chemical properties, (4) the deposited dose in vitro correlated to the deposited dose in vivo, and (5) AIC studies reliably modeled acute toxicity in vivo. Methods used in delivering, measuring, and reporting ENP aerosol doses in vitro are summarized. Dosimetry and biological response comparisons of AIC, conventional suspensions, and in vivo exposures are discussed through case studies on silver, zinc oxide, titanium dioxide, and multi-walled carbon nanotube exposures. Finally, based on these findings, recommendations are offered for design of future AIC experiments to aid standardization and comparisons of results.     

Assessing nanomaterial exposures in aquatic ecotoxicological testing: Framework and case studies based on dispersion and dissolution

The unique behavior of engineered nanomaterials (ENM) in aqueous media and dynamic changes in particle settling, agglomeration and dissolution rates is a challenge to the consistency, reliability and interpretation of standard aquatic hazard bioassay results. While the toxicological endpoints (e.g., survival, growth, reproduction, etc.) in ecotoxicity bioassays are largely applicable to ENMs, the standard methods as written for dissolved substances are confounded by the dynamic settling, agglomeration and dissolution of particulate ENMs during the bioassay. A testing framework was designed to serve as a starting point to identify approaches for the consistent conduct of aquatic hazard tests that account for the behavior of ENMs in test media and suitable data collection to support representative exposure metrology. The framework was demonstrated by conducting three case studies testing ENMs with functionally distinct characteristics and behaviors. Pretests with a temporal sampling of particle concentration, agglomeration and dissolution were conducted on each ENM in test media. Results indicated that a silver nanoparticle (AgNP) powder was not dispersible, a nano-TiO₂ powder was dispersible but unstable, and a polyvinylpyrrolidinone-coated AgNP was relatively stable in test media. Based on these functional results, Ceriodaphnia dubia bioassays were conducted to compare different exposure summary methods (nominal, arithmetic average, geometric average, time-weighted average) for calculating and expressing toxicity endpoints. Results indicated that while arithmetic means were effective for expressing the toxicity of more stable materials, time-weighted averaged concentrations were appropriate for the unstable nano-TiO₂.     

Cytotoxicity screening and cytokine profiling of nineteen nanomaterials enables hazard ranking and grouping based on inflammogenic potential

Engineered nanomaterials (ENMs) are being produced for an increasing number of applications. Therefore, it is important to assess and categorize ENMs on the basis of their hazard potential. The immune system is the foremost defence against foreign bodies. Here we performed cytokine profiling of a panel of nineteen representative ENMs procured from the Joint Research Centre (JRC) and commercial sources. Physicochemical characterization was performed using dynamic light scattering. The ENMs were all shown to be endotoxin content free. The human macrophage-differentiated THP.1 cell line was employed for cytotoxicity screening and based on the calculated IC₅₀ values, the multi-walled carbon nanotubes (MWCNTs), ZnO, Ag and SiO₂ NMs were found to be the most cytotoxic while single-walled carbon nanotubes (SWCNTs), TiO₂, BaSO₄ and CeO₂ NMs, as well as the nanocellulose materials, were non-cytotoxic (at doses up to 100?µg/mL). Multiplex profiling of cytokine and chemokine secretion indicated that the TiO₂, SiO₂, BaSO₄, CeO₂ and nanocellulose materials induced potent inflammatory responses at sub-cytotoxic doses. Hierarchical clustering of cytokine responses coupled with pathway analysis demonstrated that the panel of ENMs could be segregated into two distinct groups characterized by activation and deactivation, respectively, of PPAR (peroxisome proliferator-activated receptor)/LXR (liver X receptor/retinoid X receptor) nuclear receptor pathways (NRPs). Furthermore, using rosiglitazone, a selective PPAR-γ agonist, we could show that PPAR-γ played an important role in the activation of inflammatory responses in cells exposed to TiO₂ and SiO₂ NMs. These studies show that ENMs of diverse chemical compositions can be grouped according to their inflammatory potential.     

Nanomaterials for modulating innate immune cells in cancer immunotherapy

 Cancer immunotherapy has been intensively investigated in both preclinical and clinical studies. Whereas chemotherapies use cytotoxic drugs to kill tumor cells, cancer immunotherapy is based on the ability of the immune system to fight cancer. Tumors are intimately associated with the immune system: they can suppress the immune response and/or control immune cells to support tumor growth. Immunotherapy has yielded promising results in clinical practice, but some patients show limited responses. This may reflect the complexities of the relationship between a tumor and the immune system. In an effort to improve the current immunotherapies, researchers have exploited nanomaterials in creating new strategies to cure tumors via modulation of the immune system in tumor tissues. Although extensive studies have examined the use of immune checkpoint-based immunotherapy, rather less work has focused on manipulating the innate immune cells. This review examines the recent approaches and challenges in the use of nanomaterials to modulate innate immune cells.