Abstract: Understanding the in vivo fate and transport of nanoparticles (NPs) is challenging, but critical. We review recent studies of metal and metal oxide NPs using the model organism Caenorhabditis elegans, summarizing major findings to date. In a joint transdisciplinary effort, we highlight underutilized opportunities offered by powerful techniques lying at the intersection of mechanistic toxicology and materials science. To this end, we firstly summarize the influence of exposure conditions (media, duration, C. elegans lifestage) and NP physicochemical properties (size, coating, composition) on the response of the worm to NP treatment.
Next, we focus on the techniques employed to study NP entrance route, uptake, biodistribution and fate, emphasizing the potential of extending the toolkit available with novel and powerful techniques. Next, we review findings on several NP-induced biological responses, namely transport routes and altered molecular pathways, and illustrate the molecular biology and genetic strategies applied, critically reviewing their strengths and weaknesses.
Finally, we advocate the incorporation of a set of minimal materials and toxicological science experiments that will permit meta-analysis and synthesis of multiple studies in the future. We believe this review will facilitate coordinated integration of both well-established and underutilized approaches in mechanistic toxicology and materials science by the nanomaterials research community
Citation: L. Gonzalez-Moragas, L. L. Maurer, V. M. Harms, J. Meyer, A. Laromaine and A. Roig, Mater. Horiz., 2017, DOI: 10.1039/C7MH00166E
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 organism 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.
Date: Friday, January 20th Time: 12.00 pm Place: ICMAB – Sala d’actes Carles Miravitlles
Abstract: Some metals are exclusively toxic to biological systems and classified as being non-essential, others are essential for life. Nevertheless, above certain threshold concentrationsall (including the essential ones) become toxic. Homeostasis of essential elements and detoxification of non-essential elements are thus vital drivers of well-being, longevity and survival. By exploiting genomic, transcriptomic and toxicological tools within the model nematode C. elegans we identified and characterized intricate pathways that not only form the foundations of metallomics but facilitate further explorations within the field of nanomaterials.
Short bio: Professor Stephen Sturzenbaum holds a personal chair in Toxicogenomics at King’s College London and was recently awarded a Senior Doctorate (DSc) from Cardiff University for his work on “Toxicogenomics on Terrestrial Worms”. Stephen pioneered the use of molecular genetic tools in the common earthworm, and in doing so was instrumental in establishing the earthworm as a sentinel soil macroinvertebrate model organism of environmental importance. Stephen’s second stream of work has focussed on promoting the use of the more established C. elegans model organism to address the burgeoning themes of metallobiology, toxicogenomics and nanoparticle toxicology.Laura González, from our group, who did her thesis on evaluating nanoparticles’ toxicity on C. elegans, did aninternship at his laboratory during Feb-May 2016.
If you would like to arrange a meeting with Prof. Stephen Stürzenbaum please contact: Dr. Anna Laromaine (email@example.com)
Prof. Joel N. Meyer will give a Seminar entitled “Mechanisms of uptake and toxicity of silver nanoparticles in Caenorhabditis elegans“, today, December 15, at 12 pm at ICMAB Conference Room Carles Miravitlles.
Engineered nanomaterials offer great opportunities due to their novel properties. However, there is concern that these novel properties may also result in deleterious effects on human and ecological health that are difficult to predict based only on an understanding of the chemical makeup. We tested a number of nanoparticles (NPs) for toxicity in the nematode model Caenorhabditis elegans, and found that certain silver NPs (AgNPs) were the most toxic of the NPs that we had tested. We therefore extended our studies to characterize environmental factors that might alter AgNP toxicity, as well as the uptake and mechanism of toxicity of AgNPs in C. elegans.
Because much AgNP waste is expected to end up in aquatic ecosystems, we tested the influence of environmental variables on toxicity. We found that higher ionic strength, the presence of natural organic matter, and sulfidation of the AgNPs (expected to occur in many environments after AgNP release) all significantly reduced Ag NP toxicity. Using physicochemical, genetic, and pharmacological rescue approaches, we found that the most toxic AgNPs -generally, the smallest- caused their effects largely via dissolution. Some AgNPs (typically less soluble due to size or coating) also caused toxicity via generation of reactive oxygen species, an effect specific to nanoparticulate silver. This effect was masked by the toxicity of silver ions except when dissolution was very limited. The toxicity of the tested AgNPs was almost never greater than would result from complete dissolution of the same mass of silver. We also found that endocytosis was an important mechanism for AgNP uptake. However, the specific mechanisms by which AgNPs or released silver ion cause toxicity remain unclear. Because AgNPs are used to kill microbes, and mitochondria are endosymbiotic descendants of bacteria, current studies are focused on testing the possibility that AgNPs cause some of their toxicity via disruption of mitochondrial function.
If you would like to arrange a meeting with Prof. Joel N. Meyer please contact: Dr. Anna Laromaine(firstname.lastname@example.org).
This Friday 16th of December Laura González is going to defend her Doctoral Thesis entitled “Evaluating inorganic nanoparticles in the living organism Caenorhabditis elegans”, supervised by Dr. Anna Laromaine and Dr. Anna Roig.
Abstract: In this thesis, we have used the simple model organism Caenorhabditis elegans as an in vivo biological system to screen inorganic nanoparticles (NPs) with biomedical uses. In particular, we have assessed the behaviour of two types of particles with different composition, size and surface properties: iron oxide NPs coated with citrate and bovine serum albumin, and gold nanoparticles of two different sizes. We have studied their interactions with C. elegans including their uptake, fate, biological effects and NP-responsive molecular mechanisms, and compared our results with previous studies. To this end, we have combined toxicity tests, materials science and imaging techniques and gene expression analysis. We have been able to perform this biological evaluation in the synthetic laboratory where the particles were synthesized and characterised due to the advantageous experiments features of C. elegans.In summary, this thesis exploits the potential of C. elegans as a simple animal model to evaluate NPs in the initial stages of development and contributes to: (i) a systematic and comprehensive evaluation of NPs in C. elegans, in particular studying the influence of NP properties (size, surface coating and core composition) on their in vivo effects, (ii) extend the toolkit of techniques available to characterise nano-bio interactions in small organisms.
Laura González has obtained a fellowship to do an internship in a start-up company in Latin America or Portugal for a period of 6-12 weeks for her entrepreneurship project GMP Nanotech, within the BoosterWe progam.
The GMP Nanotech project she presented consist in the business plan of the manufacture of inorganic nanoparticles for biomedical applications with pharmaceutical quality.
The BoosterWe program supports entrepreneurs from universities in Latin America, Spain and Portugal to put in place innovative business initiatives. The program offers hands-on learning experience and business management through stays in small and medium consolidated companies that operate in another country and in complementary sectors than the entrepreneurs projects. These stays will last for 6 to 12 weeks. The beneficiaries will have a grant to help cover travel expenses and accommodation in the country of destination, as well as personalized mentoring of their new projects. The overall objective of BoosterWE is to energize the university entrepreneurship in the Ibero-American region, promoting the creation of highly innovative companies, and especially promoting the incorporation of female talent within the university entrepreneurship with scientific and technological base.
The second prize for Oral Presentation has been for Daniel Grajales Garcia (ICN2) for his talk on “Bio-Hacking and Do-It-Yourself Biologist”. The two posters awards have been for Enelia Cristina (ICN2) (second prize) and Florind Merkoçi (ICN2) (first prize). The winners were determined through popular voting.
The aim of this conference is to give the opportunity to PhD, Master and Undergraduate students working in nanoscience at the UAB Campus to present their own scientific work in a 10-15 minutes presentation or in a poster (poster sessions). The meeting took place at the Facultat de Ciències i Biociències of the Universitat Autònoma de Barcelona (UAB) on June 29th-30th.
Laura González is going for an internship at King’s College London for three months (February 1st – May 1st, 2016) in the framework of her Ph.D. She will be in the Toxicogenomics Group with Prof. Stephen Sturzenbaum. Laura will study whether the treatment with iron oxide and gold nanoparticles alters gene expression (at the transcriptome level) of certain genes involved in oxidative stress responses, and in heavy metals detoxification mechanisms, using C. elegans as a model organism.
Collaboration with other Universities and Research Centers is always a welcoming and positive experience, both for the graduate students and for the Group. We wish Laura all the best and success in this new adventure!
Laura has graduated from the ‘Màster en Direcció i Organització Industrial’ of EUSS – Escola Universitària Salesiana de Sarrià -. Her master thesis proposed a scale up fabrication process for iron oxide nanoparticles including a business plan. Yesterday she received the diploma and a prize recognition for being the top graded of her course.