Projekter pr. år
Abstract
Despite the common knowledge that the reticuloendothelial system is largely responsible for blood clearance of systemically administered nanoparticles, the sequestration mechanism remains a "black box". Using transgenic zebrafish embryos with cell type-specific fluorescent reporters and fluorescently labeled model nanoparticles (70 nm SiO2), we here demonstrate simultaneous three-color in vivo imaging of intravenously injected nanoparticles, macrophages, and scavenger endothelial cells (SECs). The trafficking processes were further revealed at ultrastructural resolution by transmission electron microscopy. We also find, using a correlative light-electron microscopy approach, that macrophages rapidly sequester nanoparticles via membrane adhesion and endocytosis (including macropinocytosis) within minutes after injection. In contrast, SECs trap single nanoparticles via scavenger receptor-mediated endocytosis, resulting in gradual sequestration with a time scale of hours. Inhibition of the scavenger receptors prevented SECs from accumulating nanoparticles but enhanced uptake in macrophages, indicating the competitive nature of nanoparticle clearance in vivo. To directly quantify the relative contributions of the two cell types to overall nanoparticle sequestration, the differential sequestration kinetics was studied within the first 30 min post-injection. This revealed a much higher and increasing relative contribution of SECs, as they by far outnumber macrophages in zebrafish embryos, suggesting the importance of the macrophage:SECs ratio in a given tissue. Further characterizing macrophages on their efficiency in nanoparticle clearance, we show that inflammatory stimuli diminish the uptake of nanoparticles per cell. Our study demonstrates the strength of transgenic zebrafish embryos for intravital real-time and ultrastructural imaging of nanomaterials that may provide mechanistic insights into nanoparticle clearance in rodent models and humans.
Originalsprog | Engelsk |
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Tidsskrift | ACS Nano |
Vol/bind | 14 |
Nummer | 2 |
Sider (fra-til) | 1665-1681 |
Antal sider | 17 |
ISSN | 1936-0851 |
DOI | |
Status | Udgivet - jan. 2020 |
Fingeraftryk
Dyk ned i forskningsemnerne om 'Differential Nanoparticle Sequestration by Macrophages and Scavenger Endothelial Cells Visualized in Vivo in Real-Time and at Ultrastructural Resolution'. Sammen danner de et unikt fingeraftryk.Projekter
- 2 Afsluttet
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NanoALERT - Imaging of Nanoparticle-Activated Leukocyte and Endothelium in Real-Time
Hayashi, Y. (PI)
01/01/2017 → 26/08/2019
Projekter: Projekt › Forskning
-
DANiim - Danio rerio (zebrafish) Innate Immunity Model for Bionanoscience
Hayashi, Y. (PI)
01/10/2014 → 31/12/2016
Projekter: Projekt › Forskning
Presse/Medier
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Zebrafish embryos help prove what happens to nanoparticles in the blood
30/09/2020
1 Mediebidrag
Presse/medie
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Zebrafish let you see the biological fate of nanoparticles in vivo
13/05/2020
1 Mediebidrag
Presse/medie