Negotiation for a global treaty on plastic pollution is currently ongoing, and public concerns about microplastics in the environment are escalating, which triggers considerable worries about their impacts on human and environmental health. In the natural environment, plastic pollutants undergo various physical, chemical, and biological processes that lead to plastic fragmentation into micro- or nano-scale particles (known as micro/nanoplastics, MNPs). MNPs have become ubiquitous and have been discovered in numerous environments globally and are also prevalent in our daily lives. They have emerged as significant contaminants, raising critical ecotoxicological concerns. Because the toxicity of MNPs is closely linked to their locations within organisms, it is necessary to develop specific experimental protocols and techniques tailored for MNPs, such as bioimaging technologies. While many studies have shown the impacts of MNPs on gastrointestinal tracts and gills as the first uptake sites, much remains to be examined regarding their impacts on other critical organs, especially when coupled with bioaccumulation. With our recent discoveries of the rapid and efficient transport of MNPs to different organs following blood circulation, this proposal intends to examine the impacts of MNPs on three critical organs in fish: the heart, liver, and brain. Specifically, we will 1) evaluate the significance of blood as a central delivery system and develop fish blood as a biomarker response platform; 2) conduct expansion microscopy (ExM) bioimaging of MNPs impacts on fish organ development at the nanoscale cellular level; and 3) diagnose the impacts of MNPs on fish cardiovascular function, neurobehavior, and liver metabolism and function. The strength of this project will be the application of various cutting-edge technologies under environmentally relevant conditions, as well as directly coupling biokinetics with the identified toxicity, which is now critically needed in our environmental risk assessments of MNPs. One of our goals is to develop a sensitive platform to rapidly assess the impacts of MNPs in fish systems. By developing various sensitive detection methods, this proposal will be able to reveal the critical impacts of MNPs on specific fish organs at the cellular, biochemical, physiological, and behavioral levels following blood transport. It is anticipated that this project will significantly contribute to our understanding and prediction of the risks posed by MNPs in aquatic environments. The results will aid in the formulation of effective strategies to manage plastic input into the environment, providing the public with scientifically sound and reliable information on MNPs risks in the environment.