TY  - JOUR
AB  - Curcumin, a natural polyphenol derived from the spice turmeric (Curcuma longa), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into “biomimetic” nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.
AU  - Evans, A.C.*
AU  - Martin, K.A.*
AU  - Saxena, M.*
AU  - Bicher, S.
AU  - Wheeler, E.*
AU  - Córdova, E.J.*
AU  - Porada, C.D.*
AU  - Almeida-Porada, G.*
AU  - Kato, T.A.*
AU  - Wilson, P.F.*
AU  - Coleman, M.A.*
C1  - 66585
C2  - 53219
TI  - Curcumin nanodiscs improve solubility and serve as radiological protectants against ionizing radiation exposures in a cell-cycle dependent manner.
JO  - Nanomaterials
VL  - 12
IS  - 20
PY  - 2022
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Nanoparticle toxicity assessments have moved closer to physiological conditions while trying to avoid the use of animal models. An example of new in vitro exposure techniques developed is the exposure of cultured cells at the air–liquid interface (ALI), particularly in the case of respiratory airways. While the commercially available VITROCELL® Cloud System has been applied for the delivery of aerosolized substances to adherent cells under ALI conditions, it has not yet been tested on lung surfactant and semi-adherent cells such as alveolar macrophages, which are playing a pivotal role in the nanoparticle-induced immune response. Objectives: In this work, we developed a comprehensive methodology for coating semi-adherent lung cells cultured at the ALI with aerosolized surfactant and subsequent dose-controlled exposure to nanoparticles (NPs). This protocol is optimized for subsequent transcriptomic studies. Methods: Semi-adherent rat alveolar macrophages NR8383 were grown at the ALI and coated with lung surfactant through nebulization using the VITROCELL® Cloud 6 System before being exposed to TiO2 NM105 NPs. After NP exposures, RNA was extracted and its quantity and quality were measured. Results: The VITROCELL® Cloud system allowed for uniform and ultrathin coating of cells with aerosolized surfactant mimicking physiological conditions in the lung. While nebulization of 57 µL of 30 mg/mL TiO2 and 114 µL of 15 mg/mL TiO2 nanoparticles yielded identical cell delivered dose, the reproducibility of dose as well as the quality of RNA extracted were better for 114 µL.
AU  - Leroux, M.M.*
AU  - Hocquel, R.*
AU  - Bourge, K.*
AU  - Kokot, B.*
AU  - Kokot, H.*
AU  - Koklič, T.*
AU  - Štrancar, J.*
AU  - Ding, Y.
AU  - Kumar, P.
AU  - Schmid, O.
AU  - Rihn, B.H.*
AU  - Ferrari, L.*
AU  - Joubert, O.*
C1  - 64860
C2  - 52520
TI  - Aerosol–cell exposure system applied to semi-adherent cells for aerosolization of lung surfactant and nanoparticles followed by high quality RNA extraction.
JO  - Nanomaterials
VL  - 12
IS  - 8
PY  - 2022
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Conjugation of photosensitizers (PS) with nanoparticles has been largely used as a strategy to stabilize PS in the biological medium resulting in photosensitizing nanoparticles of enhanced photoactivity. Herein, (Meso-5, 10, 15, 20-tetrakis (3-hydroxyphenyl) phorphyryn (mTHPP) was conjugated with diamond nanoparticles (ND) by covalent bond. Nanoconjugate ND-mTHPP showed suitable stability in aqueous suspension with 58 nm of hydrodynamic diameter and Zeta potential of −23 mV. The antibacterial activity of ND-mTHPP was evaluated against Escherichia coli for different incubation times (0–24 h). The optimal activity was observed after 2 h of incubation and irradiation (660 nm; 51 J/cm  ) performed right after the addition of ND-mTHPP (100 µg/mL) to the bacterial suspension. The inhibitory activity was 56% whereas ampicillin at the same conditions provided only 14% of bacterial growth inhibition. SEM images showed agglomerate of ND-mTHPP adsorbed on the bacterial cell wall, suggesting that the antimicrobial activity of ND-mTHPP was afforded by inducing membrane damage. Cytotoxicity against murine embryonic fibroblast cells (MEF) was also evaluated and ND-mTHPP was shown to be noncytotoxic since viability of cells cultured for 24 h in the presence of the nanoconjugate (100 µg/mL) was 78%. Considering the enhanced antibacterial activity and the absence of cytotoxic effect, it is possible to consider the ND-mTHPP nanoconjugate as promising platform for application in antimicrobial photodynamic therapy (aPDT). 2
AU  - Hurtado, C.R.*
AU  - Hurtado, G.R.*
AU  - de Cena, G.L.*
AU  - Queiroz, R.C.*
AU  - Silva, A.V.
AU  - Diniz, M.F.*
AU  - Dos Santos, V.R.*
AU  - Trava-Airoldi, V.*
AU  - Baptista, M.d.S.*
AU  - Tsolekile, N.*
AU  - Oluwafemi, O.S.*
AU  - Conceição, K.*
AU  - Tada, D.B.*
C1  - 62145
C2  - 50666
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Diamond nanoparticles-porphyrin mthpp conjugate as photosensitizing platform: Cytotoxicity and antibacterial activity.
JO  - Nanomaterials
VL  - 11
IS  - 6
PB  - Mdpi
PY  - 2021
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Magneto-plasmonic nanocomposites can possess properties inherent to both individual components (iron oxide and gold nanoparticles) and are reported to demonstrate high potential in targeted drug delivery and therapy. Herein, we report on Fe O /Au magneto-plasmonic nanocomposites (MPNC) synthesized with the use of amino acid tryptophan via chemical and photochemical reduction of Au ions in the presence of nanosized magnetite. The magnetic field (MF) induced aggregation was accompanied by an increase in the absorption in the near-infrared (NIR) spectral region, which was demonstrated to provide an enhanced photothermal (PT) effect under NIR laser irradiation (at 808 nm). A possibility for therapeutic application of the MPNC was illustrated using cancer cells in vitro. Cultured HeLa cells were treated by MPNC in the presence of MF and without it, following laser irradiation and imaging using confocal laser scanning microscopy. After scanning laser irradiation of the MPNC/MF treated cells, a formation and rise of photothermally-induced microbubbles on the cell surfaces was observed, leading to a damage of the cell membrane and cell destruction. We conclude that the synthesized magneto-plasmonic Fe O /Au nanosystems exhibit magnetic field-induced reversible aggregation accompanied by an increase in NIR absorption, allowing for an opportunity to magnetophoretically control and locally enhance a NIR light-induced thermal effect, which holds high promise for the application in photothermal therapy. 3 4 3 4
AU  - Mukha, I.*
AU  - Chepurna, O.*
AU  - Vityuk, N.*
AU  - Khodko, A.*
AU  - Storozhuk, L.*
AU  - Dzhagan, V.*
AU  - Zahn, D.R.T.*
AU  - Ntziachristos, V.
AU  - Chmyrov, A.
AU  - Ohulchanskyy, T.Y.*
C1  - 61908
C2  - 50298
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Multifunctional magneto-plasmonic fe3o4/au nanocomposites: Approaching magnetophoretically-enhanced photothermal therapy.
JO  - Nanomaterials
VL  - 11
IS  - 5
PB  - Mdpi
PY  - 2021
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1 beta release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale (R) system, and NPs were deposited on the co-culture using XposeALI (R). No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1 beta, IL-6, TNF alpha, MCP-1) were observed after exposure of the co-culture in ALI (max 5 mu g/cm(2)) or submerged (max 22 mu g/cm(2)) conditions. In contrast, CeO2 NPs cause clear IL-1 beta release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.
AU  - Cappellini, F.*
AU  - Di Bucchianico, S.
AU  - Karri, V.*
AU  - Latvala, S.*
AU  - Malmlöf, M.*
AU  - Kippler, M.*
AU  - Elihn, K.*
AU  - Hedberg, J.*
AU  - Wallinder, I.O.*
AU  - Gerde, P.*
AU  - Karlsson, H.L.*
C1  - 58705
C2  - 48257
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Dry generation of CeO2 nanoparticles and deposition onto a co-culture of A549 and THP-1 cells in air-liquid interface – dosimetry consideration and comparison to submerged exposure.
JO  - Nanomaterials
VL  - 10
IS  - 4
PB  - Mdpi
PY  - 2020
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Production of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene expression using RNA sequencing following long term (six weeks) low dose (0.5 mu g Ni/mL) exposure of human lung cells (BEAS-2B) to Ni and NiO NPs as well as soluble NiCl2. Genotoxicity and cell transformation as well as cellular dose of Ni are also analyzed. Exposure to NiCl2 resulted in the largest number of differentially expressed genes (197), despite limited uptake, suggesting a major role of extracellular receptors and downstream signaling. Gene expression changes for all Ni exposures included genes coding for calcium-binding proteins (S100A14 and S100A2) as well as TIMP3, CCND2, EPCAM, IL4R and DDIT4. Several top enriched pathways for NiCl2 were defined by upregulation of, e.g., interleukin-1A and -1B, as well as Vascular Endothelial Growth Factor A (VEGFA). All Ni exposures caused DNA strand breaks (comet assay), whereas no induction of micronuclei was observed. Taken together, this study provides an insight into Ni-induced toxicity and mechanisms occurring at lower and more realistic exposure levels.
AU  - Gliga, A.R.*
AU  - Di Bucchianico, S.
AU  - Akerlund, E.*
AU  - Karlsson, H.L.*
C1  - 58743
C2  - 48288
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Transcriptome profiling and toxicity following long-term, low dose 
      exposure of human lung cells to Ni and NiO nanoparticles – a 
      comparison to NiCl2.
JO  - Nanomaterials
VL  - 10
IS  - 4
PB  - Mdpi
PY  - 2020
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - The growing use of silver nanoparticles (Ag-NPs) in consumer products raises concerns about their toxicological potential. The purpose of the study was to investigate the size- and coating-dependent pulmonary toxicity of Ag-NPs in vitro and in vivo, using an ovalbumin (OVA)-mouse allergy model. Supernatants from (5.6-45 µg/mL) Ag50-PVP, Ag200-PVP or Ag50-citrate-treated NR8383 alveolar macrophages were tested for lactate dehydrogenase and glucuronidase activity, tumor necrosis factor (TNF)-α release and reactive oxygen species (ROS) production. For the in vivo study, NPs were intratracheally instilled in non-sensitized (NS) and OVA-sensitized (S) mice (1-50 µg/mouse) prior to OVA-challenge and bronchoalveolar lavage fluid (BALF) inflammatory infiltrate was evaluated five days after challenge. In vitro results showed a dose-dependent cytotoxicity of Ag-NPs, which was highest for Ag50-polyvinilpyrrolidone (PVP), followed by Ag50-citrate, and lowest for Ag200-PVP. In vivo 10-50 µg Ag50-PVP triggered a dose-dependent pulmonary inflammatory milieu in NS and S mice, which was significantly higher in S mice and was dampened upon instillation of Ag200-PVP. Surprisingly, instillation of 1 µg Ag50-PVP significantly reduced OVA-induced inflammatory infiltrate in S mice and had no adverse effect in NS mice. Ag50-citrate showed similar beneficial effects at low concentrations and attenuated pro-inflammatory effects at high concentrations. The lung microbiome was altered by NPs instillation dependent on coating and/or mouse batch, showing the most pronounced effects upon instillation of 50 µg Ag50-citrate, which caused an increased abundance of operational taxonomic units assigned to Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. However, no correlation with the biphasic effect of low and high Ag-NPs dose was found. Altogether, both in vitro and in vivo data on the pulmonary effects of Ag-NPs suggest the critical role of the size, dose and surface functionalization of Ag-NPs, especially in susceptible allergic individuals. From the perspective of occupational health, care should be taken by the production of Ag-NPs-containing consumer products.
AU  - Alessandrini, F.
AU  - Vennemann, A.*
AU  - Gschwendtner, S.
AU  - Neumann, A.U.
AU  - Rothballer, M.
AU  - Seher, T.
AU  - Wimmer, M.
AU  - Kublik, S.
AU  - Traidl-Hoffmann, C.
AU  - Schloter, M.
AU  - Wiemann, M.*
AU  - Schmidt-Weber, C.B.
C1  - 52018
C2  - 43674
CY  - Basel
TI  - Pro-Inflammatory versus immunomodulatory effects of silver nanoparticles in the lung: The critical role of dose, size and surface modification.
JO  - Nanomaterials
VL  - 7
IS  - 10
PB  - Mdpi Ag
PY  - 2017
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Silica (SiO₂) nanoparticles (NPs) usage includes, but is not limited to, industrial and biomedical applications. Toxic effects of SiO₂ NPs have been explored either in vitro or in vivo, assessing different surface modifications to reduce their harmful effects. Here, murine bone marrow-derived dendritic (BMDC) and a mouse model of mild allergic inflammation were used to study inflammasome activation and lung inflammation. Our results showed that SiO₂ plain NPs induced NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome activation, increasing interleukin (IL)-1β release in vitro, and, to a lesser extent, in vivo. In addition, SiO₂ plain NPs triggered a pulmonary inflammatory milieu in both non-sensitized (NS) and sensitized (S) mice, by inducing the expression of key inflammatory cytokines and chemokines. Electron microscopy showed that SiO₂ NPs were mostly localized in alveolar macrophages, within vesicles and/or in phagolysosomes. Both the in vitro and the in vivo effects of SiO NPs were attenuated by coating NPs with phosphonate or amino groups, whereas PEGylation, although it mitigated inflammasome activation in vitro, was not a successful coating strategy in vivo. These findings highlight that multiple assays are required to determine the effect of surface modifications in limiting NPs inflammatory potential. Taken together, these data are obtained by comparing in vitro and in vivo effects of SiO₂ NPs suggest the use of amino and phosphonate coating of silica NPs for commercial purposes and targeted applications, as they significantly reduce their proinflammatory potential.
AU  - Marzaioli, V.
AU  - Groß, C.J.*
AU  - Weichenmeier, I.
AU  - Schmidt-Weber, C.B.
AU  - Gutermuth, J.*
AU  - Groß, O.*
AU  - Alessandrini, F.
C1  - 52236
C2  - 43886
CY  - Basel
TI  - Specific surface modifications of silica nanoparticles diminish inflammasome activation and in vivo expression of selected inflammatory genes.
JO  - Nanomaterials
VL  - 7
IS  - 11
PB  - Mdpi Ag
PY  - 2017
SN  - 2079-4991
ER  - 

TY  - JOUR
AB  - Nanoparticles (NPs) may affect the lung via their chemical composition on the surface. Here, we compared the bioactivity of zirconium oxide (ZrO₂) NPs coated with either aminopropilsilane (APTS), tetraoxidecanoic acid (TODS), polyethyleneglycol (PGA), or acrylic acid (Acryl). Supernatants from NPs-treated cultured alveolar macrophages (NR8383) tested for lactate dehydrogenase, glucuronidase, tumor necrosis factor α, and H₂O₂ formation revealed dose-dependent effects, with only gradual differences among particles whose gravitational settling and cellular uptake were similar. We selected TODS- and Acryl-coated NPs for intratracheal administration into the rat lung. Darkfield and hyperspectral microscopy combined with immunocytochemistry showed that both NPs qualities accumulate mainly within the alveolar macrophage compartment, although minute amounts also occurred in neutrophilic granulocytes. Dose-dependent signs of inflammation were found in the broncho-alveolar lavage fluid on day 3 but no longer on day 21 post-application of ≥1.2 mg per lung; again only minor differences occurred between TODS- and Acryl-coated NPs. In contrast, the response of allergic mice was overall higher compared to control mice and dependent on the surface modification. Increases in eosinophils, lymphocytes and macrophages were highest following ZrO₂-PGA administration, followed by ZrO₂-Acryl, ZrO₂-TODS, and ZrO₂-APTS. We conclude that surface functionalization of ZrO₂ NPs has minor effects on the inflammatory lung response of rats and mice, but is most relevant for an allergic mouse model. Allergic individuals may therefore be more susceptible to exposure to NPs with specific surface modifications.
AU  - Vennemann, A.*
AU  - Alessandrini, F.
AU  - Wiemann, M.*
C1  - 51913
C2  - 43574
CY  - Basel
TI  - Differential effects of surface-functionalized zirconium oxide nanoparticles on alveolar macrophages, rat lung, and a mouse allergy model.
JO  - Nanomaterials
VL  - 7
IS  - 9
PB  - Mdpi Ag
PY  - 2017
SN  - 2079-4991
ER  -