Abstract
Nanotechnology holds substantial promise across medicine, industry, and environmental science, yet its rapid advancement raises important concerns about potential impacts on both human health and ecosystems. This review explores evidence on alternative bridging models that connect cellular responses to organism-level outcomes, enabling integrated evaluation of nanomaterial safety and efficacy. Beyond conventional in vitro and mammalian systems, we focus on a diverse range of invertebrates, including Hydra spp., planarians, Caenorhabditis elegans, Drosophila melanogaster, Bombyx mori, and bivalve mollusks, and small vertebrates, notably zebrafish and avian embryos. These ethically compliant, cost-effective, and biologically relevant platforms have been compared regarding the main experimental readouts they provide, from survival and regeneration to behavior, metabolism, and molecular stress responses. Across studies, applications in nanotoxicology and ecotoxicology reveal conserved mechanisms of nanoparticle action, including oxidative stress, genotoxicity, inflammation, and immune modulation, while clarifying links between environmental exposure and human health. In parallel, these models advance nanomedicine development, improving our understanding of biodistribution, targeting precision, and therapeutic efficacy. Finally, we discuss their current limitations, such as a lack of standardization, and propose practical considerations for model selection to strengthen risk assessment, support safer-by-design strategies, and promote the responsible development of next-generation nanotechnologies that balance innovation with sustainability.