Toxicological and physiological responses to combined ultrasound and lipid-coated ZnO nanoparticle exposure in Caenorhabditis elegans

In the field of nanomedicine, nanoparticles have gained increasing attention due to their potential as therapeutic and diagnostic tools across a wide range of biomedical applications. However, despite their growing popularity and promising results, understanding their biological interactions and accurately evaluating their safety and efficacy remain significantly challenging. In this context, the invertebrate model organism Caenorhabditis elegans (C. elegans) provides an ideal toxicological model system because of its favorable characteristics. In this research, we used C. elegans to investigate the effects of potentially toxic iron-doped zinc oxide nanoparticles (ZnO NPs) and their biocompatible counterpart, lipid-coated ZnO (L-ZnO NPs). In addition, we combine these NPs with physical stimulation, i.e., ultrasound, to which these NPs are responsive, aiming to evaluate possible combined treatments in animals. The toxicity of ZnO and L-ZnO NPs was evaluated on this invertebrate model. In addition, external acoustic pressure stimulation was studied, evaluating the sole effects of ultrasound stimulation and its combined application with NPs. Multiple biological parameters were analyzed to assess treatment effects, including viability, biodistribution, egg-laying, body bends, and production of radical species associated with oxidative stress. This study demonstrates that L-ZnO NPs exhibit greater biological safety than ZnO NPs, while their combined application with ultrasound does not result in an additive effect. Additionally, the results highlight the potential of using C. elegans as a primary model to evaluate nanomedicine treatments and obtain initial insights into the effects of nanoparticles in animal systems.