文章基本信息

标题：Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model
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作者：Zhiling Guo ; Peng Zhang ; Swaroop Chakraborty 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：28
DOI：10.1073/pnas.2105245118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Although the brain is protected by a tight physiological guardian named the blood–brain barrier (BBB), deposition of engineered nanomaterials (ENMs) in the brain and consequent neurotoxicity has been reported. To date, it is still unclear whether and how ENMs enter the brain by crossing the BBB. In this study, we found that metallic ENMs transform in the BBB as affected by their shape, size, and intrinsic solubility, which in turn modulates their transport form, efficiency, and pathways through the BBB and, consequently, their neurotoxicity. The library of quantitative data on the chemical transformations presented here will support in silico modeling and prediction of the neurotoxicity of NMs and facilitate the tailored design of safe NMs. 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.
关键词：ennanomaterials;blood–brain barrier;neurotoxicity;single-particle ICP-MS;synchrotron