NANION aims at contributing to the understanding in how far surface properties of NPs (physical parameters, biological molecules attached, ions leaching, etc.) affect uptake and toxicity of NPs. This proposal is aimed to investigate the characteristics of the key physico-chemical parameters and surface functionalities of a well-chosen list of NPs that control uptake and dependent biological effects of different complexity ranging from vitality assays to analysis of the proteome. Hypothesis driven research is proposed using state-of-the-art facilities. The detailed systematic knowledge on the NP properties used within NANION will finally enable us to understand relevant properties rather than performing endless repetitive solely descriptive experiments and contribute to the development of safe nanomaterials.