PUBLICATION

Liposome-Mediated Drug Delivery in Larval Zebrafish to Manipulate Macrophage Function

Authors
Wu, Z., Koh, B., Lawrence, L.M., Kanamala, M., Pool, B., Svirskis, D., Dalbeth, N., Astin, J.W., Crosier, K.E., Crosier, P.S., Hall, C.J.
ID
ZDB-PUB-190207-5
Date
2019
Source
Zebrafish   16(2): 171-181 (Journal)
Registered Authors
Astin, Jonathan, Crosier, Kathy, Crosier, Phil, Hall, Chris
Keywords
MSU crystals, drug delivery, liposomes, macrophage, zebrafish
MeSH Terms
  • Animals
  • Antioxidants/chemistry
  • Drug Delivery Systems/methods
  • Drug Delivery Systems/veterinary*
  • Enzyme Inhibitors/chemistry
  • Epoxy Compounds/chemistry*
  • Liposomes/metabolism*
  • Macrophages/metabolism*
  • Models, Animal
  • Organophosphorus Compounds/chemistry*
  • Piperidines/chemistry*
  • Zebrafish*
PubMed
30724716 Full text @ Zebrafish
Abstract
Chemical interventions are regularly used to examine and manipulate macrophage function in larval zebrafish. Given chemicals are typically administered by simple immersion or injection, it is not possible to resolve whether their impact on macrophage function is direct or indirect. Liposomes provide an attractive strategy to target drugs to specific cellular compartments, including macrophages. As an example, injecting liposomal clodronate into animal models, including zebrafish, is routinely used to deliver toxic levels of clodronate specifically to macrophages for targeted cell ablation. Here we show that liposomes can also target the delivery of drugs to zebrafish macrophages to selectively manipulate their function. We utilized the drugs etomoxir (a fatty acid oxidation inhibitor) and MitoTEMPO (a scavenger of mitochondrial reactive oxygen species [mROS]), that we have previously shown, through free drug delivery, suppress monosodium urate (MSU) crystal-driven macrophage activation. We generated poloxamer 188 modified liposomes that were readily phagocytosed by macrophages, but not by neutrophils. Loading these liposomes with etomoxir or MitoTEMPO and injecting into larvae suppressed macrophage activation in response to MSU crystals, as evidenced by proinflammatory cytokine expression and macrophage-driven neutrophil recruitment. This work reveals the utility of packaging drugs into liposomes as a strategy to selectively manipulate macrophage function.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes