Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity

Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O2•-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H2O2 instead of O2•-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity. Altogether these results suggest that O2•- generated during NPs induced mitochondrial collapse is rapidly dismutated to H2O2, which in the presence of iron ions undergoes a Fenton reaction to produce an extremely reactive hydroxyl radical (•OH). Clarification of the mechanism of NPs-dependent generation of •OH and demonstration of the crucial role of iron ions in NPs toxicity will facilitate our understanding of NPs toxicity and the design of safe nanomaterials

Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy

The 225Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with 225Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work we propose to apply TiO2 nanoparticles (NPs) as carrier for 225Ac and its decay products. The surface of TiO2 nanoparticles with 25 nm diameter was modified with Substance P(5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles functionalized with Substance P(5-11) were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). The obtained results show that one TiO2-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO2-PEG-SP(5-11) conjugates were labelled with 225Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO2 surface. The labelled bioconjugates almost quantitatively retain 225Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of 221Fr, a first decay daughter of 225Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized 225Ac-TiO2-PEG-SP(5-11) have shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours.JRC.G.I.5-Advanced Nuclear Knowledg

Tricarbonylrhenium(I) complexes with the <i>N</i>,6-dimethylpyridine-2-carbothioamide ligand: combined experimental and calculation studies

<p>A new series of tricarbonyl complexes of rhenium(I) in the “2 + 1” system with the bidentate ligand <i>N</i>,6-dimethylpyridine-2-carbothioamide ((CH₃)NC₅H₄-CS-NH-CH₃, MeLH<i>(Me)</i>_NS) and a monodentate ligand (halides Cl, Br, or I, and the pseudohalide NCS anion) was synthesized. The use of mixed ligands led to the formation of neutral tricarbonylrhenium(I) complexes [Re(CO)₃(MeLH<i>(Me)</i>_NS)X] (X = Cl, Br, I, NCS) (<b>1</b>–<b>4</b>). Single-crystal X-ray diffraction was used to determine the crystal structures of all four compounds and those results were compared with molecular structures obtained from DFT calculations using the PBE0/def2-TZVPD approach. The complexes were also characterized by spectroscopic (FT-IR, NMR, and UV–vis) and analytical (HPLC, TGA, EA, ESI-MS) techniques. IR and UV–vis spectra were also calculated by DFT and TD-DFT methods. The cytotoxicity of these complexes was estimated using human ovarian cancer cell lines (A2780 and A2780cis), cervical cancer cells (HeLa), and non-cancerous human embryonic kidney cells (Hek-293). The toxicity of most complexes was moderate or low toward cancer cell lines (IC₅₀ = 46–231 μM) and similar against non-cancerous cells (IC₅₀ = 41-121 μM). Only the complex with chlorido ligand remarkably inhibited growth of ovarian cancer cells (IC₅₀ = 3 and 12 μM for A2780 and A2780cis, respectively). The cytotoxicity of <b>1</b> was higher than that of cisplatin.</p

MOESM1 of Glucose availability determines silver nanoparticles toxicity in HepG2

Additional file 1. Expression on mRNA level of all tested genes. Results are shown as fold change of expression in cells sustained on low glucose medium (5.5 mM) when compared with cells sustained on high glucose medium (25 mM)