Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model

Zhiling Guo, Peng Zhang, Swaroop Chakraborty, Andrew J Chetwynd, Fazel Abdolahpur Monikh, Christopher Stark, Hanene Ali-Boucetta, Sandra Wilson, Iseult Lynch, Eugenia Valsami-Jones

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Understanding the potential of nanomaterials (NMs) to cross the blood–brain barrier (BBB), as a function of their physicochemical properties and subsequent behavior, fate, and adverse effect beyond that point, is vital for evaluating the neurological effects arising from their unintentional entry into the brain, which is yet to be fully explored. This is not only due to the complex nature of the brain but also the existing analytical limitations for characterization and quantification of NMs in the complex brain environment. By using a fit-for-purpose analytical workflow and an in vitro BBB model, we show that the physiochemical properties of metallic NMs influence their biotransformation in biological matrices, which in turn modulates the transport form, efficiency, amounts, and pathways of NMs through the BBB and, consequently, their neurotoxicity. The data presented here will support in silico modeling and prediction of the neurotoxicity of NMs and facilitate the tailored design of safe NMs.

Original languageEnglish
Article numbere2105245118
JournalProceedings of the National Academy of Sciences
Issue number28
Early online date6 Jul 2021
Publication statusPublished - 13 Jul 2021

Bibliographical note

Funding Information: This work was supported by the Horizon 2020 (H2020) Marie Skłodowska-Curie Individual Fellowships research program (NanoBBB, Grant Agreement 798505, Z.G. Fellow; NanoLabels, Grant Agreement 750455, P.Z. Fellow). Additional support from the H2020 European Union research infrastructure for nanosafety project NanoCommons (Grant Agreement 731032), for data management and the Horizon 2020 project ACEnano (Grant H2020-NMBP-2016-720952), and for analytical support are acknowledged. This work was carried out with the support of Diamond Light Source instrument STXM (beamline I08, proposal SP20567-2) and instrument core X-ray absorption spectroscopy (beamline B18, proposal SP20204-2). We thank Giannantonio Cibin and Diego Gianolio at the B18 beamline for their support during XANES experiments and Tohru Araki and Burkhard Kaulich at I08 beamline for their support during STXM experiments. Rachel Smith from Public Health England is acknowledged for early discussion of project design.


  • Blood–brain barrier
  • Nanomaterials
  • Neurotoxicity
  • Single-particle ICP-MS
  • Synchrotron
  • single-particle ICP-MS
  • blood–brain barrier
  • neurotoxicity
  • synchrotron
  • nanomaterials

ASJC Scopus subject areas

  • General


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