Human exposure to airborne carbon nanotubes (CNT) is increasing because of their applications in different sectors; therefore, they constitute a biological hazard. Consequently, developing studies on CNT toxicity become a necessity. CNTs can have different properties in term of length, size and charge. Here, we compared the cellular effect of multiwall (MWCNTs) and single wall CNTs (SWCNTs). MWCNTs consist of multiple layers of graphene, while SWCNTs are monolayers. The effects of MWCNTs and SWCNTs were evaluated by the water‐soluble tetrazolium salt cell proliferation assay on NR8383 cells, rat alveolar macrophage cell line (NR8383). After 24 hours of exposure, MWCNTs showed higher toxicity (50% inhibitory concentration [IC 50 ] = 3.2 cm 2 /cm 2 ) than SWCNTs (IC 50 = 44 cm 2 /cm 2 ). Only SWCNTs have induced NR8383 cells apoptosis as assayed by flow cytometry using the annexin V/IP staining test. The expression of genes involved in oxidative burst ( Ncf1 ), inflammation ( Nfκb , Tnf‐α , Il‐6 and Il‐1β ), mitochondrial damage ( Opa ) and apoptotic balance ( Pdcd4 , Bcl‐2 and Casp‐8 ) was determined. We found that MWCNT exposure predominantly induce inflammation, while SWCNTs induce apoptosis and impaired mitochondrial function. Our results clearly suggest that MWCNTs are ideal candidates for acute inflammation induction. In vivo studies are required to confirm this hypothesis. However, we conclude that toxicity of CNTs is dependent on their physical and chemical characteristics.

The toxicity of heavy metals present in binary semiconductor nanoparticles also known as quantum dots (QDs) has hindered their wide applications hence the advent of non-toxic ternary quantum dots. These new group of quantum dots have been shown to possess some therapeutic action against cancer cell lines but not significant enough to be referred to as an ideal therapeutic agent. In this report, we address this problem by conjugating red emitting CuInS/ZnS QDs to a 5,10,15,20-tetrakis(3hydroxyphenyl)porphyrin-photosensitizer for improved bioactivities. The glutathione capped CuInS/ ZnS QDs were synthesized in an aqueous medium using a kitchen pressure cooker at different Cu: In ratios (1:4 and 1:8) and at varied temperatures (95 °C, 190 °C and 235 °C). Optical properties show that the as-synthesized CuInS/ZnS QDs become red-shifted compared to the core (CuInS) after passivation with emission in the red region while the cytotoxicity study revealed excellent cell viability against normal kidney fibroblasts (BHK21). The highly fluorescent, water-soluble QDs were conjugated to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) via esterification reactions at room temperature. The resultant water-soluble conjugate was then used for the cytotoxicity, fluorescent imaging and gene expression study against human monocytic leukemia cells (THP-1). Our result showed that the conjugate possessed high cytotoxicity against THP-1 cells with enhanced localized cell uptake compared to the bare QDs. In addition, the gene expression study revealed that the conjugate induced inflammation compared to the QDs as NFKB gene was over-expressed upon cell inflammation while the singlet oxygen (1 o 2) study showed the conjugate possessed large amount of 1 o 2 , three times than the bare porphyrin. Thus, the as-synthesized conjugate looks promising as a therapeutic agent for cancer therapy. The use of nanomaterials for biological application has in the past decade transpired as a promising avenue to explore for biological application due to their size, shape, specific surface area, aspect ratio and surface chemistry. Of the reported nanomaterial, semiconductor nanomaterials also known as quantum dots (QDs) still remain the most promising due to their excellent optoelectronic properties and spectral tunability which allows for their use in the ultraviolet and near infra-red region 1,2. These inherent properties have made QDs more appealing

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Metal oxide nanoparticles (NPs), such as ZnO, ZnFe 2 O 4 , and Fe 2 O 3 , are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe 2 O 4 , and Fe 2 O 3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC 50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe 2 O 4 , and Fe 2 O 3 ; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe 2 O 4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe 2 O 4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe 2 O 4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe 2 O 4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.

Functionalized multi-walled carbon nanotubes (MWCNT) have become the focus of increased research interest, particularly in their application as tools in different areas, such as the biomedical field. Despite the benefits associated with functionalization of MWCNT, particularly in overcoming issues relating to solubility, several studies have demonstrated that these functionalized nanoparticles display different toxicity profiles. For this study, we aim to compare NR8383 cells responses to three well-characterized MWCNT with varying functional groups. This study employed cytotoxicity assays, transcriptomics and proteomics to assess their toxicity using NR8383 rat alveolar macrophages as an in vitro model. The study findings indicated that all MWCNT altered ribosomal protein translation, cytoskeleton arrangement and induced pro-inflammatory response. Only functionalized MWCNT alter mTOR signaling pathway in conjunction with increased Lamtor gene expression. Furthermore, the type of functionalization was also important, with cationic MWCNT activating the transcription factor EB and inducing autophagy while the anionic MWCNT altering eukaryotic translation initiation factor 4 (EIF4) and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling pathway as well as upregulation Tlr2 gene expression. This study proposes that MWCNT toxicity mechanisms are functionalization dependent and provides evidence that inflammatory response is a key event of carbon nanotubes toxicity.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

There are many studies concerning titanium dioxide (TiO2) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification and validation of common markers under different exposure conditions are relevant for the development of smart and quick nanotoxicity tests. In this work, cell viability was assessed in vitro by WST-1 and LDH assays after the exposure of NR8383 cells to TiO2 NP sample. To evaluate in vitro gene expression profile, NR8383 cells were exposed to TiO2 NP during 4 h at 3 cm2 of TiO2 NP/cm2 of cells or 19 μg/mL, in two settings—submerged cultures and ALI. For the in vivo study, Fischer 344 rats were exposed by inhalation to a nanostructured aerosol at a concentration of 10 mg/m3, 6 h/day, 5 days/week for 4 weeks. This was followed immediately by gene expression analysis. The results showed a low cytotoxic potential of TiO2 NP on NR8383 cells. Despite the absence of toxicity at the doses studied, the different exposures to TiO2 NP induce 18 common differentially expressed genes (DEG) which are involved in mitosis regulation, cell proliferation and apoptosis and inflammation transport of membrane proteins. Among these genes, we noticed the upregulation of Ccl4, Osm, Ccl7 and Bcl3 genes which could be suggested as early response biomarkers after exposure to TiO2 NP. On the other hand, the comparison of the three models helped us to validate the alternative ones, namely submerged and ALI approaches.

Designing and manufacturing multifunctional nanoparticles (NPs) are of considerable interest for both academic and industrial research. Among NPs used in this field, iron oxide NPs show low toxicity compared to metallic ones and are thus of high interest for biomedical applications. In this work, superparamagnetic Fe 3−δ O 4 -based core/shell NPs were successfully prepared and characterized by the combination of different techniques, and their physical properties were investigated. We demonstrate the efficiency of the layer-by-layer process to graft polyelectrolytes on the surface of iron oxide NPs. The influence of the polyelectrolyte chain configuration on the magnetic properties of the Fe 3−δ O 4 /polymer core/shell NPs was enlightened. The simple and fast process described in this work is efficient for the grafting of polyelectrolytes from surfaces, and thus, derived Fe 3−δ O 4 NPs display both the physical properties of the core and of the macromolecular shell. Finally, the cytotoxicity toward the human THP-1 monocytic cell line of the core/shell NPs was assessed. The results showed that the polymer-capped Fe 3−δ O 4 NPs exhibited almost no toxicity after 24 h of exposure at concentrations up to 25 μg mL −1 . Our results show that these smart superparamagnetic nanocarriers with stealth properties are promising for applications in multimodal cancer therapy, including drug delivery.

are widely employed for treating ovarian cancer. [1] Nevertheless, anticancer agents have potential side effects such as hair loss, infertility, diarrhea, and nausea. [2,3] To minimize these side effects, various types of controlled drug delivery systems have been engineered to specifically target the drug to cancer cells based on cells surface receptors interactions in order to avoid toxicity toward normal cells. [4,5] Superparamagnetic iron oxide nanoparticles (SPIONs) have been developed extensively due to their wide spectrum of applications in the biomedical field, including biosensors, [6,7] tissue engineering, [8] drug delivery, [9,10] and in medical science for magnetic resonance imaging (MRI). [11,12,13] Another interesting property deals with the fact that they can generate heat upon application of a local high frequency alternating magnetic field (HAMF). The latter is particularly interesting when considering the cancer therapy as the tumors cannot survive heating up to 45 °C. [14] Furthermore, due to their nanosize, SPIONs can easily play with the enhanced permeability and retention (EPR) effect to be delivered to the solid tumor. [15] Moreover, their surface can be easily modified both to specifically direct a cargo Here, a versatile strategy to engineer smart theranostic nanocarriers is reported. The core/shell nanosystem is composed of a superparamagnetic iron oxide (Fe 3−δ O 4 ) nanoparticle (NP) core bearing the biocompatible thermo-responsive poly(2-(2-methoxy)ethyl methacrylate-oligo(ethylene glycol methacrylate), P(MEO 2 MA x -OEGMA 100−x ) copolymer (where x and 100-x represent the molar fractions of MEO 2 MA and OEGMA, respectively). Folic acid (FA) is end-conjugated to the P(MEO 2 MA x -OEGMA 100−x ) copolymer, leading to Fe 3 − δ O 4 @P(MEO 2 MA x -OEGMA 100−x )-FA, to facilitate active targeting of NPs to cancer cells. A highly potent hydrophobic anticancer agent doxorubicin (DOX) is incorporated in the thermo-responsive P(MEO 2 MA x -OEGMA y ) brushes via supramolecular interactions to increase its solubility and the assessment of therapeutic potentials. These experiments confirm the magnetic hyperthermia properties of nanocarrier and reveal that only a small amount (10% ± 4%) of DOX is diffused at room temperature, while almost full drug (100%) is released after 52 h at 41 °C. Interestingly, it is found that P(MEO 2 MA 60 -OEGMA 40 ) polymers offer to NPs a promising stealth behavior against Human Serum Albumin and Fibrinogen model proteins.