Glucocorticoids (GCs) are effective anti-inflammatory drugs, but their clinical use is limited by their side effects. Using liposomes to target GCs to inflammatory sites is a promising approach to... Show moreGlucocorticoids (GCs) are effective anti-inflammatory drugs, but their clinical use is limited by their side effects. Using liposomes to target GCs to inflammatory sites is a promising approach to improve their therapeutic ratio. We used zebrafish embryos to visualize the biodistribution of liposomes and to determine the anti-inflammatory and adverse effects of the GC prednisolone phosphate (PLP) encapsulated in these liposomes. Our results showed that PEGylated liposomes remained in circulation for long periods of time, whereas a novel type of liposomes (which we named AmbiMACs) selectively targeted macrophages. Upon laser wounding of the tail, both types of liposomes were shown to accumulate near the wounding site. Encapsulation of PLP in the PEGylated liposomes and AmbiMACs increased its potency to inhibit the inflammatory response. However, encapsulation of PLP in either type of liposome reduced its inhibitory effect on tissue regeneration, and encapsulation in PEGylated liposomes attenuated the activation of glucocorticoid-responsive gene expression throughout the body. Thus, by exploiting the unique possibilities of the zebrafish animal model to study the biodistribution as well as the anti-inflammatory and adverse effects of liposomal formulations of PLP, we showed that PEGylated liposomes and AmbiMACs increase the therapeutic ratio of this GC drug. Show less
Bernardello, M.; Gora, R.J.; Hage, P. van; Castro-Olvera, G.; Gualda, E.J.; Schaaf, M.J.M.; Loza-Alvarez, P. 2021
Single-molecule microscopy techniques have emerged as useful tools to image individual molecules and analyze their dynamics inside cells, but their application has mostly been restricted to cell... Show moreSingle-molecule microscopy techniques have emerged as useful tools to image individual molecules and analyze their dynamics inside cells, but their application has mostly been restricted to cell cultures. Here, a light-sheet fluorescence microscopy setup is presented for imaging individual proteins inside living zebrafish embryos. The optical configuration makes this design accessible to many laboratories and a dedicated sample-mounting system ensures sample viability and mounting flexibility. Using this setup, we have analyzed the dynamics of individual glucocorticoid receptors, which demonstrates that this approach creates multiple possibilities for the analysis of intracellular protein dynamics in intact living organisms. (c) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement Show less
Radoslaw, J.; Jong, B. de; Hage, P. van; Rhiemus, M.; Steenis, F. van; Noort, S.J.T. van; ... ; Schaaf, M.J.M 2021
Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that... Show morePlastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity. Show less
Brun, N.R.; Hage, P. van; Hunting, E.R.; Haramis, A.-P.G.; Vink, S.C.; Vijver, M.G.; ... ; Tudorache, C. 2019
Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that... Show morePlastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity. Show less
