Intravenously injected nanoparticles (NPs) hold great promise for clinical diagnostic and therapeutic applications. While several NPs for such clinical applications have emerged in various designs (metallic, polymeric, quantum dots etc.) [1], a critical issue in their in vivo use is the lack of fundamental studies examining the effects of physicochemical parameters (shape, size, surface properties etc.) on blood circulation, kinetics of accumulation and elimination as well as toxicity [2–4]. We hypothesize that blood, the first medium of interaction in the body, is a major determinant of biotransport and biodistribution. Recent and past in vitro studies have shown that NPs interact with serum proteins (including complement factors), cause platelet aggregation and red blood cell hemolysis, and are taken up by phagocytic cells. However, to our knowledge a detailed in vivo study of the interaction of metallic nanoparticles with blood components as a function of their surface properties does not yet exist.

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