Sources of biases in the in vitro testing of nanomaterials: the role of the biomolecular corona

Abstract

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 vitroin vivo mismatch, which currently limits the formulation of NMs for clinical settings.

Graphical abstract: Sources of biases in the in vitro testing of nanomaterials: the role of the biomolecular corona

Supplementary files

Article information

Article type
Communication
Submitted
19 Nov 2023
Accepted
12 Mar 2024
First published
13 Mar 2024
This article is Open Access
Creative Commons BY-NC license

Nanoscale Horiz., 2024, Advance Article

Sources of biases in the in vitro testing of nanomaterials: the role of the biomolecular corona

V. Castagnola, V. Tomati, L. Boselli, C. Braccia, S. Decherchi, P. P. Pompa, N. Pedemonte, F. Benfenati and A. Armirotti, Nanoscale Horiz., 2024, Advance Article , DOI: 10.1039/D3NH00510K

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