PUBLICATION
Biodistribution of surfactant-free poly(lactic-acid) nanoparticles and uptake by endothelial cells and phagocytes in zebrafish: Evidence for endothelium to macrophage transfer
- Authors
- Rességuier, J., Levraud, J.P., Dal, N.K., Fenaroli, F., Primard, C., Wohlmann, J., Carron, G., Griffiths, G.W., Le Guellec, D., Verrier, B.
- ID
- ZDB-PUB-210115-6
- Date
- 2021
- Source
- Journal of controlled release : official journal of the Controlled Release Society 331: 228-245 (Journal)
- Registered Authors
- Le Guellec, Dominique, Levraud, Jean-Pierre
- Keywords
- Biodistribution, Endothelial cell to macrophage transfer, Nanoparticles, Surfactant-free, Uptake-degradation kinetics, Zebrafish
- MeSH Terms
-
- Animals
- Endothelial Cells
- Endothelium
- Macrophages
- Mice
- Nanoparticles*
- Polyesters
- Surface-Active Agents
- Tissue Distribution
- Zebrafish*
- PubMed
- 33444668 Full text @ J. Control Release
Citation
Rességuier, J., Levraud, J.P., Dal, N.K., Fenaroli, F., Primard, C., Wohlmann, J., Carron, G., Griffiths, G.W., Le Guellec, D., Verrier, B. (2021) Biodistribution of surfactant-free poly(lactic-acid) nanoparticles and uptake by endothelial cells and phagocytes in zebrafish: Evidence for endothelium to macrophage transfer. Journal of controlled release : official journal of the Controlled Release Society. 331:228-245.
Abstract
In the development of therapeutic nanoparticles (NP), there is a large gap between in vitro testing and in vivo experimentation. Despite its prominence as a model, the mouse shows severe limitations for imaging NP and the cells with which they interact. Recently, the transparent zebrafish larva, which is well suited for high-resolution live-imaging, has emerged as a powerful alternative model to investigate the in vivo behavior of NP. Poly(D,L lactic acid) (PLA) is widely accepted as a safe polymer to prepare therapeutic NP. However, to prevent aggregation, many NP require surfactants, which may have undesirable biological effects. Here, we evaluate 'safe-by-design', surfactant-free PLA-NP that were injected intravenously into zebrafish larvae. Interaction of fluorescent NPs with different cell types labelled in reporter animals could be followed in real-time at high resolution; furthermore, by encapsulating colloidal gold into the matrix of PLA-NP we could follow their fate in more detail by electron microscopy, from uptake to degradation. The rapid clearance of fluorescent PLA-NP from the circulation coincided with internalization by endothelial cells lining the whole vasculature and macrophages. After 30 min, when no NP remained in circulation, we observed that macrophages continued to internalize significant amounts of NP. More detailed video-imaging revealed a new mechanism of NP transfer where NP are transmitted along with parts of the cytoplasm from endothelial cells to macrophages.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping