The organic destiny of nanomaterials (NMs) is pushed by particular interactions by which biomolecules, naturally adhering onto their floor, have interaction with cell membrane receptors and intracellular organelles. The molecular composition of this layer, referred to as the biomolecular corona (BMC), is determined by each the bodily–chemical options of the NMs and the organic media wherein the NMs are dispersed and cells develop. On this work, we exhibit that the widespread use of 10% fetal bovine serum in an in vitro assay can’t recapitulate the complexity of in vivo systemic administration, with NMs being transported by the blood. For this function, we undertook a comparative journey involving proteomics, lipidomics, excessive throughput multiparametric in vitro screening, and single molecular function evaluation to research the molecular particulars behind this in vivo/in vitro bias. Our work not directly highlights the necessity to introduce novel, extra physiological-like media nearer in composition to human plasma to provide life like in vitro screening knowledge for NMs. We additionally purpose to set the premise to scale back this in vitro–in vivo mismatch, which at present limits the formulation of NMs for medical settings.
