Nanotechnology is an enabling platform that will provide a broad range of novel applications and improved technologies for biomedical science due to the unique physical and chemical properties inherent to nanomaterials. Pertinent to the development of promising biomedical nanotechnologies, and to the safety of nanomaterials in general, is a thorough understanding of nanomaterial-biological interactions. Yet, the principal characteristics that may be predictive of nanomaterial interactions with biological systems have not been elucidated because of the current lack of data, the enormous diversity of nanomaterials, and the lack of coordinated efforts to share findings and translate data into knowledge. The embryonic zebrafish model is a dynamic in vivo system that offers the power of whole-animal investigations with the convenience of cell culture to rapidly evaluate interactions between engineered nanomaterials and biological systems. Investigations using this model system can reveal subtle interactions at multiple levels of biological organization, i.e. molecular, cellular, systems, organismal. Our approach couples the many advantages of the embryonic zebrafish assay with an ideal nanoparticle platform in order to systematically assess the relative influence of various physiochemical parameters on overall biological responses to nanomaterial exposure. High-purity, ligand-functionalized gold nanoparticles (AuNPs) synthesized in aqueous environments can be precisely engineered such that individual aspects of the material can be evaluated independently. It is well understood that data from this emerging field will be extremely diverse including a multitude of widely varying nanomaterials that are being/or will be tested in a broad array of animal systems and in vitro assays. Knowledge of nanomaterial-biological interactions will likely only be arrived at upon inclusion and consideration of the entire body of data produced from global efforts in this research area. To address these needs in the nascent field of nanobiotechnology, our group has developed a collaborative knowledgebase of Nanomaterial-Biological Interactions (NB). The NBI knowledgebase serves as a repository for annotated data on nanomaterial characterization, synthesis methods, and nanomaterial-biological interactions define at multiple levels of biological organization. Relevant computational, analytic and data mining tools will be incorporated into NBI to the framework for species, route, dose and scenario extrapolations and for identification of key data required to predict the biological interactions of nanomaterials. PUBLIC HEALTH RELEVANCE: New nanomaterials are rapidly being developed for a wide range of biomedical applications (e.g. high-performance diagnostic probes, site-selective therapeutics, prosthetics, regenerative medicine, imaging, etc.), so it is surprising that so little is known about how or why nanomaterials interact with biological systems and even less is known about how to design them to exhibit a desired effect in whole animals. The immediate need to gain comprehensive information on biological-nanomaterial interactions requires systematic, collaborative scientific investigation to define nanomaterial-biological interactions and describe how specific properties of nanomaterials govern biological responses. Timely evaluation and dissemination of information on nanomaterial-biological interactions will provide much needed data, improve public trust of the nanotechnology industry, and provide nanomaterial designers in academia and industry with information to direct the development of high-performance, safe nanomaterials and resulting biomedical technologies.