Nanoparticles have distinct properties and these properties are rapidly revolutionizing the biomedical applications. Despite of development in nanoscience, there is quite little understanding about the interaction of nanomaterials with living systems for the safe and proficient application. It is believed that in a biological medium, proteins interact with nanoparticles and compete for the surface of nanoparticles leading to formation of protein capping which modify the physicochemical properties of nanoparticles. The biological fluid observes nanoparticles with modified surface hence composition of capping proteins become responsible for the further cellular response. In this chapter, we present different factors which are responsible for variations in corona composition such as physicochemical properties of NPs (e.g., size, shape, surface charge, composition, surface functional groups, coatings and hydrophilicity/hydrophobicity) and influence of biological environment. Aside from that impact of ignored issues at bionano interface like administration route, temperature, cell observer, plasma concentration and plasma gradient effect will also be discussed.
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