Biosafety assessment of Gd@C-82(OH)(22) nanoparticles on Caenorhabditis elegans

CAS Key Laboratory for Biological Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing, China.
Nanoscale (Impact Factor: 7.39). 06/2011; 3(6):2636-41. DOI: 10.1039/c1nr10239g
Source: PubMed


Gd@C(82)(OH)(22), a water-soluble endohedral metallofullerene derivative, has been proven to possess significant antineoplastic activity in mice. Toxicity studies of the nanoparticle have shown some evidence of low or non toxicity in mice and cell models. Here we employed Caenorhabditis elegans (C. elegans) as a model organism to further evaluate the short- and long-term toxicity of Gd@C(82)(OH)(22) and possible behavior changes under normal and stress culture conditions. With treatment of Gd@C(82)(OH)(22) at 0.01, 0.1, 1.0 and 10 μg ml(-1) within one generation (short-term), C. elegans showed no significant decrease in longevity or thermotolerance compared to the controls. Furthermore, when Gd@C(82)(OH)(22) treatment was extended up to six generations (long-term), non-toxic effects to the nematodes were found. In addition, data from body length measurement, feeding rate and egg-laying assays with short-term treatment demonstrated that the nanoparticles have no significant impact on the individual growth, feeding behavior and reproductive ability, respectively. In summary, this work has shown that Gd@C(82)(OH)(22) is tolerated well by worms and it has no apparent toxic effects on longevity, stress resistance, growth and behaviors that were observed in both adult and young worms. Our work lays the foundations for further developments of this anti-neoplastic agent for clinical applications.

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    • "Our current study with the WW domain as an example consistently indicates that metallofullerenol Gd@C82(OH)22 might cause undesired side effect on protein functions. The blockage of signalling proteins might not immediately cause cell or animal deaths37, but it may induce latent malfunctioning of related cellular processes including RNA transcription38 and apoptotic regulation39 of damaged cells in the long run. The accumulative damage might be implicated in various diseases such as neurodegenerative diseases as well as cancers4041. "
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    ABSTRACT: Endohedral metallofullerenol Gd@C(82)(OH)(22) has recently been shown to effectively inhibit tumor growth; however, its potential adverse bioeffects remain to be understood before its wider applications. Here, we present our study on the interaction between Gd@C(82)(OH)(22) and WW domain, a representative protein domain involved in signaling and regulatory pathway, using all-atom explicit solvent molecular dynamics simulations. We find that Gd@C(82)(OH)(22) has an intrinsic binding preference to the binding groove, particularly the key signature residues Y28 and W39. In its binding competition with the native ligand PRM, Gd@C(82)(OH)(22) is shown to easily win the competition over PRM in occupying the active site, implying that Gd@C(82)(OH)(22) can impose a potential inhibitory effect on the WW domain. Further analyses with binding free energy landscapes reveal that Gd@C(82)(OH)(22) can not only directly block the binding site of the WW domain, but also effectively distract the PRM from its native binding pocket.
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    • "Among the examined endpoints, body bend and head thrash are very sensitive, and can be used to evaluate the potential toxicity of TiO2-NPs exposure at the concentration of 1 ng/L. Similarly, after exposure from L1-larvae to adulthood, nano-CeO2 exhibited adverse effects on nematodes at environmental relevant concentrations [35]. "
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