In vivo interactions between food availability and nanoparticles in Caenorhabditis elegans

During the last decades, nanoparticles (NPs) have been widely used in various fields, especially in medical applications such as drugs, imaging agents, and drug-delivery carriers. However, they also raised public concerns regarding the potential adverse influences on human health. Collective efforts from worldwide researchers in materials and biological science have been invested in investigating the toxicity mechanisms of different NPs. In this thesis, we dedicated major efforts to apply (Caenorhabditis elegans) C. elegans as a robust and simple model organism for toxicity assessments of assorted NPs. The general objective of this thesis was to study effects of food availability on nano-bio interactions between superparamagnetic iron oxide nanoparticles (SPIONs) or 10 nm AuNPs and C. elegans, and prove that this small animal can be used to study alimentary effects. Firstly, we studied the effects of food availability on toxicities induced by exposure to SPIONs after 24 h (acute exposure) or 72 h (prolonged exposure). We found that food provided some protection to C. elegans determined by measuring multiple toxicity endpoints such as survival and reproduction. Worms in the acute exposure condition had a higher uptake efficiency of SPIONS facilitated by food compared with the condition without the addition of food. The utilization of synchrotron Fourier transform infrared microspectroscopy (SR-μFTIR), allowed us to demonstrate that long-exposure (24 h versus 4 h) and high concentrations of SPIONs (500 μg/mL versus 100 μg/mL) induce more severe oxidative stress determined by increased levels of lipid oxidation. Secondly, we investigated food’s influences on worms after 24 h exposure to 10 nm AuNPs. The protective role of food was identified in reducing toxic effects, such as survival and reproduction. Using SR-μFTIR, we found that small-sized AuNPs (10 nm versus 150 nm) or long-exposure (24 h versus 4 h) caused an increased level of lipid oxidation which was related to responses against oxidative stress. On the other hand, we preliminarily evaluated the possibility of performing the photothermal therapy in worms containing 150 nm AuNPs. We found photoablated damages on the laser irradiation spots of worms, suggesting that multiple experimental settings needed to be optimized. At the end of the thesis, also we presented some collaborations where we performed some experiments with different nanomaterials such as lutein and (metal-organic frameworks) MOFs and evaluated them on C. elegans. We studied antioxidative properties of lutein in C. elegans disease models associated with Leigh Syndrome and demonstrated the possibility to apply synchrotron Fourier transform infrared microspectroscopy (SR-μFTIR) on this topic. On the other hand, we performed the preliminary toxicity assessment of MOFs, MIL-127 and chitosan (CS) coated MIL-127 (CS-MIL-127). Additionally, we investigated about effects of the chitosan (CS) coating on C. elegans’ uptake and excretion efficiencies of MIL-127 and CS-MIL-127. We reported the potential of applying C. elegans as an oral administration model of studying metal-organic frameworks’ (MOFs’) in vivo toxicities. In summary, food availability could decrease adverse effects, partially associated with oxidative stress, induce by SPIONs or AuNPs on C. elegans. It also suggested that C. elegans has a great potential of being employed as an oral administration model of testing various materials. Furthermore, combined with other advanced techniques, we could have a more general understanding of the toxicity mechanism and broaden the application range of material science techniques for biological research.Finally, I acknowledge the funding from the Chinese Scholarship Council for pursuing my PhD degree.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).N