In vivo testing of gold nanoparticles using the Caenorhabditis elegans model organism.
Gold nanoparticles (AuNPs) are present in many man-made products and cosmetics and are also used by the food and medical industries. Tight regulations regarding the use of mammalian animals for product testing can hamper the study of the specific interactions between engineered nanoparticles and biological systems. Invertebrate models, such as the nematode Caenorhabditis elegans (C. elegans), can offer alternative approaches during the early phases of nanoparticle discovery. Here, we thoroughly evaluated the biodistribution of 11-nm and 150-nm citrate-capped AuNPs in the model organism C. elegans at multiple scales, moving from micrometric to nanometric resolution and from the organismal to cellular level. We confirmed that the nanoparticles were not able to cross the intestinal and dermal barriers. We investigated the effect of AuNPs on the survival and reproductive performance of C. elegans, and correlated these effects with the uptake of AuNPs in terms of their number, surface area, and metal mass. In general, exposure to 11-nm AuNPs resulted in a higher toxicity than the larger 150-nm AuNPs. NP aggregation inside C. elegans was determined using absorbance microspectroscopy, which allowed the plasmonic properties of AuNPs to be correlated with their confinement inside the intestinal lumen, where anatomical traits, acidic pH and the presence of biomolecules play an essential role on NP aggregation. Finally, quantitative PCR of selected molecular markers indicated that exposure to AuNPs did not significantly affect endocytosis and intestinal barrier integrity.



This work highlights how the simple, yet information-rich, animal model C. elegans is ideally suited for preliminary screening of nanoparticles or chemicals mitigating most of the difficulties associated with mammalian animal models, namely the ethical issues, the high cost, and time constraints. This is of particular relevance to the cosmetic, food, and pharmaceutical industries, which all have to justify the use of animals, especially during the discovery, development and initial screening phases. This work provides a detailed and thorough analysis of 11-nm and 150-nm AuNPs at multiple levels of organization (the whole organism, organs, tissues, cells and molecules).
Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus UAB, 08193 Bellaterra, Barcelona, Spain.
Laura
L
Gonzalez-Moragas
ICFO-Institut de Ciències Fotòniques, Av. Carl Friedrich Gauss, 3, 08860 Castelldefels, Barcelona, Spain.
Pascal
P
Berto
ICFO-Institut de Ciències Fotòniques, Av. Carl Friedrich Gauss, 3, 08860 Castelldefels, Barcelona, Spain.
Clara
C
Vilches
ICFO-Institut de Ciències Fotòniques, Av. Carl Friedrich Gauss, 3, 08860 Castelldefels, Barcelona, Spain.
Romain
R
Quidant
European Molecular Biology Laboratory, EMBL, Meyerhofstraße, 1, 69117 Heidelberg, Germany.
Androniki
A
Kolovou
European Molecular Biology Laboratory, EMBL, Meyerhofstraße, 1, 69117 Heidelberg, Germany.
Rachel
R
Santarella-Mellwig
European Molecular Biology Laboratory, EMBL, Meyerhofstraße, 1, 69117 Heidelberg, Germany.
Yannick
Y
Schwab
King's College London, Faculty of Life Sciences & Medicine, Analytical and Environmental Sciences Division, 150 Stamford Street, London SE1 9NH, United Kingdom.
Stephen
S
Stürzenbaum
Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus UAB, 08193 Bellaterra, Barcelona, Spain.
Anna
A
Roig
Institut de Ciència de Materials de Barcelona, ICMAB-CSIC, Campus UAB, 08193 Bellaterra, Barcelona, Spain. Electronic address: alaromaine@icmab.es.
Anna
A
Laromaine
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000633:toxicity*; D008422:Materials Testing / Q000379:methods; D023421:Models, Animal; D053758:Nanoparticles / Q000633:toxicity*; D015996:Survival Rate; D014018:Tissue Distribution; D018675:Toxicity Tests / Q000379:methods*
D006046:Gold
Biological interactions; Caenorhabditis elegans; Digestive system; Endocytosis; Enterocytes; Gold nanoparticles