title: Engineered multifunctional RGD-gold nanoparticles for the detection of tumour-specific alpha(v)beta(3) expression: chemical characterisation and ecotoxicological risk assessment.
abstract: Radiolabelled nanoparticles conjugated to peptides that target specific molecules can be used as agents for diagnosis. For example, technetium-99m-labelled gold nanoparticles conjugated to the cyclic [Arg-Gly-Asp-Phe-Lys(Cys)] (c[RGDfK(C)]) peptide are used for the molecular imaging of tumour-specific alpha(epsilon)beta(3) expression. Gold nanoparticles (AuNPs, 18-20 nm) are assumed to be safe at the concentrations used in diagnostic studies, and several studies of human toxicology and health implications have been discussed in a wide number of reports. However, no data are available on the potential ecotoxicity of radio-AuNPs conjugated to thiol-peptides after complete radionuclide decay. The aim of this study was to determine the ecotoxicological risk, measured by oxidative stress (OS) induction in Hyalella azteca, of a well-characterised multifunctional RGD-AuNP system (Tc-HYNIC-GGC-AuNP-c[RGDfK(C)]). TEM, UV-Vis, Raman, XPS, FT-IR and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalised with the conjugated peptides. An acute toxicity test predicted an LC50 (72 h) of 1.83 cm2 per millilitre of medium. There were no statistically significant increases in OS and antioxidant defences after sub-acute exposure to a surface area concentration of 1/10 of the LC50. Tc-HYNIC-GGC-AuNP-c[RGDfK(C)] (20 nm) was demonstrated to be a chemically stable and nontoxic system in biological media after complete radionuclide decay because it does not promote the expression of OS and antioxidant defence enzymes, such as catalase, glutathione peroxidase and superoxide dismutase in Hyalella azteca.
authors.affiliation: Departamento de Materiales Radiactivos, Instituto Nacional de Investigaciones Nucleares, Estado de México 52750, Mexico.
authors.forename: Enrique
authors.initials: E
authors.lastname: Morales-Avila
authors.forename: Guillermina
authors.initials: G
authors.lastname: Ferro-Flores
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Ocampo-García
authors.forename: Leobardo M
authors.initials: LM
authors.lastname: Gómez-Oliván
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001181:Arthropods / Q000187:drug effects*; D004463:Ecology / Q000379:methods; D004784:Environmental Monitoring / Q000379:methods; D006046:Gold / Q000737:chemistry*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis*; D007928:Lethal Dose 50; D053768:Metal Nanoparticles / Q000737:chemistry*; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry; D018570:Risk Assessment; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013997:Time Factors
chemical_list: D000975:Antioxidants; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D010455:Peptides; D006046:Gold; C047981:arginyl-glycyl-aspartic acid