Nanoparticle Drug Delivery Systems in Zebrafish Models

Nanoparticle drug delivery systems encompass a range of lipid- and polymer-based carriers engineered to encapsulate therapeutic agents and direct them to specific tissues. Zebrafish (Danio rerio) embryos and larvae have emerged as powerful in vivo platforms for real-time imaging of nanoparticle biodistribution, cellular uptake and toxicity, owing to their optical transparency, genetic tractability and conserved vertebrate physiology. Key parameters—particle size, shape, surface charge and composition—govern circulation half-life, interactions with plasma proteins (the “protein corona”) and recognition by innate immune cells, notably macrophages and endothelial scavenger systems. The zebrafish model enables high-resolution tracking of nanoparticle fate, quantification of endothelial versus macrophage uptake, and assessment of endosomal escape efficiency. It also serves as an intermediate screening step bridging in vitro assays and rodent studies, facilitating rapid optimisation of surface modifications—such as polyethylene glycol (PEG) grafting, targeting peptides or stimuli-responsive lipids—and predicting mammalian pharmacokinetics. Collectively, zebrafish studies accelerate design cycles for hepatotropic, tumour-targeting and immunomodulatory nanomedicines, support safety evaluations and inform strategies to overcome physiological barriers to clinical translation.

Research from Nature Portfolio

Recent studies have demonstrated the utility of compositionally simple liposomes whose surface charge can be switched in situ by light in zebrafish embryos. Prior to illumination, neutral liposomes circulate freely, evading phagocytic clearance. Upon photoactivation, a rapid shift to cationic charge triggers selective adsorption to endothelial cells or uptake by blood-resident macrophages, coupled with efficient intracellular release of otherwise membrane-impermeable cargos. This externally controlled, spatiotemporal tuning of nanoparticle targeting underlines the potential for precise regulation of biodistribution without adding design complexity.

Nanoparticle Drug Delivery Systems in Zebrafish Models publication trend

The graph below shows the total number of articles in nanoparticle drug delivery systems in zebrafish models across all publications each year (not limited to Nature Index journals).

Technical terms

Zebrafish embryo model: Transparent larval stage of Danio rerio used for live imaging of nanoparticle circulation, cell interactions and toxicity.

Liposome: Spherical vesicle composed of one or more phospholipid bilayers employed to encapsulate drugs and control release.

Endosomal escape: Process by which internalised nanoparticles disrupt endosomal membranes to release therapeutic payloads into the cytosol.

Protein corona: Layer of biomolecules, primarily blood proteins, adsorbed onto nanoparticle surfaces that influences biodistribution and cellular uptake.

PEGylation: Attachment of polyethylene glycol chains to nanoparticles to enhance steric stability, prolong circulation and reduce immune recognition.

Macrophage: Innate immune cell responsible for phagocytosis of foreign particles, including nanoparticles, and for mediating clearance.

References

1. Light-triggered switching of liposome surface charge directs delivery of membrane impermeable payloads in vivo. Nature Communications (2020).
2. Lipid conjugate dissociation analysis improves the in vivo understanding of lipid-based nanomedicine. Journal of Controlled Release (2024).
3. Zebrafish Embryos Allow Prediction of Nanoparticle Circulation Times in Mice and Facilitate Quantification of Nanoparticle–Cell Interactions. Small (2020).
4. 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 (2021).