Pulmonary toxicity and translocation of nanodiamonds in mice
ABSTRACT Because of the possible health threat of nanodiamonds (NDs) to organisms, the pulmonary toxicity and translocation of NDs in different sizes in mice were investigated after intratracheal instillation administration. Biochemical assays, ultrastructural and histopathological evaluations of the lungs of the control and the ND exposed mice were carried out at 1, 7, 14 or 28 days post-exposure. Exposure to 1.0 mg/kg NDs with an average diameter of 4 nm produced a temporary lung index increase at 1 day post-exposure. NDs did not have evident adverse effects in the lungs within the studied period according to histopathological and ultrastructural investigations. Furthermore, no lipid peroxidation of the lung was observed. On the whole, intratracheally instilled NDs are of low pulmonary toxicity. In addition, the amount of NDs in alveolar decreased with time elapsed and the macrophages burdened with NDs were clearly observed in the bronchia from 1 day to 28 days post-exposure. Thus we affirm the critical role of alveolar macrophages in the main excretion pathway of NDs from the lungs, i.e. they engulf the NDs, migrate upward to the trachea by escalator/mucociliary system and finally enter the pharynx.
SourceAvailable from: Alia Ghoneum[Show abstract] [Hide abstract]
ABSTRACT: Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young's Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young's modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs.Nanotechnology 10/2014; 25(46). DOI:10.1088/0957-4484/25/46/465101 · 3.67 Impact Factor
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ABSTRACT: Recently the scientific community became aware of the potential ability of nanoparticles to cause toxicity in living organisms. Therefore, many of the implications for aquatic ecosystems and its effects on living organisms are still to be evaluated and fully understood. In this study, the toxicity of nanodiamonds (NDs) was assessed in the freshwater bivalve (Corbicula fluminea) following exposure to different nominal concentrations of NDs (0.01, 0.1, 1, 10 mg l−1) throughout 14 days. The NDs were characterized (gravimetry, pH, zeta potential, electron microscopy, atomic force microscopy) confirming manufacturer information and showing NDs with a size of 4 to 6 nm. Oxidative stress enzymes activities (glutathione-s-transferase, catalase) and lipid peroxidation were determined. The results show a trend to increase in GST activities after 7 days of exposure in bivalves exposed to NDs concentrations (> 0.1 mg l−1), while for catalase a significant increase was found in bivalves exposed from 0.01 to 1.0 mg l−1 following an exposure of 14 days. The histological analysis revealed alterations in digestive gland cells, such as vacuolization and thickening. The Lipid peroxidation showed a trend to increase for the different tested NDs concentrations which is compatible with the observed cellular damage.Journal of Hazardous Materials 10/2014; 284. DOI:10.1016/j.jhazmat.2014.10.055 · 4.33 Impact Factor
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ABSTRACT: The aim is to develop irradiated nanodiamonds (INDs) as a molecularly targeted contrast agent for high-resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. The surface of acid treated radiation-damaged nanodiamonds was grafted with PEG to improve its stability and circulation time in blood, followed by conjugation to an anti-HER2 peptide with a final nanoparticle size of approximately 92 nm. Immunocompetent mice bearing orthotopic HER2-positive or negative tumors were administered INDs and PA imaged using an 820-nm near-infrared laser. PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 h. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are nontoxic. PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high-resolution (sub-mm) and phenotype-specific monitoring of cancer growth.Nanomedicine 03/2015; 10(4):573-587. DOI:10.2217/nnm.14.141 · 5.82 Impact Factor