The biological fate of nanomaterials (NMs) is driven by specific interactions through which biomolecules, naturally adhering onto their surface, engage with cell membrane receptors and intracellular organelles. The molecular composition of this layer, called the biomolecular corona (BMC), depends on both the physical–chemical features of the NMs and the biological media in which the NMs are dispersed and cells grow. In this work, we demonstrate that the widespread use of 10% fetal bovine serum in an in vitro assay cannot recapitulate the complexity of in vivo systemic administration, with NMs being transported by the blood. For this purpose, we undertook a comparative journey involving proteomics, lipidomics, high throughput multiparametric in vitro screening, and single molecular feature analysis to investigate the molecular details behind this in vivo/in vitro bias. Our work indirectly highlights the need to introduce novel, more physiological-like media closer in composition to human plasma to produce realistic in vitro screening data for NMs. We also aim to set the basis to reduce this in vitro–in vivo mismatch, which currently limits the formulation of NMs for clinical settings.

中文翻译：

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纳米材料体外测试中的偏差来源：生物分子电晕的作用

纳米材料 (NM) 的生物命运是由特定的相互作用驱动的，通过这种相互作用，自然粘附在其表面的生物分子与细胞膜受体和细胞内细胞器结合。该层的分子组成称为生物分子冠 (BMC)，取决于 NM 的物理化学特征以及 NM 分散和细胞生长的生物介质。在这项工作中，我们证明，在体外测定中广泛使用 10% 胎牛血清并不能概括体内全身给药的复杂性，因为 NM 通过血液运输。为此，我们进行了涉及蛋白质组学、脂质组学、高通量多参数体外筛选和单分子特征分析的比较之旅，以研究这种体内/体外偏差背后的分子细节。我们的工作间接强调需要引入成分更接近人血浆的新型、更类似于生理学的介质，以产生真实的NM体外筛选数据。我们还旨在为减少这种体外-体内不匹配奠定基础，这种不匹配目前限制了临床环境中 NM 的配制。