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Updated: Mar 29, 2026
In Vivo Targeting of Xenografted Human Cancer Cells with Functionalized Fluorescent Silica Nanoparticles in Zebrafish
Published on: May 8, 2020
Zebrafish as a model system for characterization of nanoparticles against cancer
Lasse Evensen1, Patrick L Johansen1, Gerbrand Koster1
1Department of Biosciences, University of Oslo, Blindernveien 31, 0371 Oslo, Norway. g.w.griffiths@ibv.uio.no.
Abstract:
Therapeutic nanoparticles (NPs) have great potential to deliver drugs against human diseases. Encapsulation of drugs in NPs protects them from being metabolized, while they are delivered specifically to a target site, thereby reducing toxicity and other side-effects. However, non-specific tissue accumulation of NPs, for example in macrophages, especially in the spleen and liver is a general problem with many NPs being developed for cancer therapy. To address the problem of non-specific tissue accumulation of NPs we describe the development of the zebrafish embryo as a transparent vertebrate system for characterization of NPs against cancer. We show that injection of human cancer cells results in tumor-like structures, and that subsequently injected fluorescent NPs, either made of polystyrene or liposomes can be imaged in real-time. NP biodistribution and general in vivo properties can be easily monitored in embryos having selective fluorescent labeling of specific tissues. We demonstrate in vitro, by using optical tweezer micromanipulation, microscopy and flow cytometry that polyethylene glycol (PEG) coating of NPs decreases the level of adhesion of NPs to macrophages, and also to cancer cells. In vivo in zebrafish embryos, PEG coating resulted in longer NP circulation times, decreased macrophage uptake, and reduced adhesion to the endothelium. Importantly, liposomes were observed to accumulate passively and selectively in tumor-like structures comprised of human cancer cells. These results show that zebrafish embryo is a powerful system for microscopy-based screening of NPs on the route to preclinical testing.
Insights
Zebrafish embryos offer a transparent system to study nanoparticle (NP) delivery for cancer therapy. Polyethylene glycol (PEG) coating reduces NP accumulation in macrophages and improves tumor targeting, aiding preclinical NP screening.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Therapeutic nanoparticles (NPs) show promise for targeted drug delivery, reducing toxicity.
- Non-specific accumulation of NPs, particularly in macrophages of the spleen and liver, hinders cancer therapy efficacy.
- Developing effective NP delivery systems requires robust preclinical evaluation methods.
Purpose of the Study:
- To establish the zebrafish embryo as a transparent vertebrate model for characterizing nanoparticle behavior in vivo.
- To investigate the impact of polyethylene glycol (PEG) coating on nanoparticle biodistribution and interaction with cancer cells and macrophages.
- To evaluate the potential of zebrafish embryos for high-throughput screening of nanoparticles for cancer therapy.
Main Methods:
- Human cancer cells were injected into zebrafish embryos to create tumor-like structures.
- Fluorescently labeled nanoparticles (polystyrene and liposomes) were injected and imaged in real-time.
- In vitro studies utilized optical tweezer micromanipulation, microscopy, and flow cytometry to assess NP-cell interactions.
- In vivo imaging in zebrafish embryos tracked NP biodistribution, circulation time, and tissue accumulation.
- Zebrafish embryos with fluorescently labeled tissues allowed for detailed monitoring of NP interactions.
Main Results:
- Zebrafish embryos successfully supported the growth of human cancer cells into tumor-like structures.
- PEG-coated NPs exhibited reduced adhesion to macrophages and cancer cells in vitro.
- In vivo, PEG-coated NPs demonstrated longer circulation times and decreased uptake by macrophages and endothelium.
- Liposomes selectively accumulated in tumor-like structures within the zebrafish embryos.
- The transparent nature of zebrafish embryos facilitated real-time imaging and monitoring of NP biodistribution.
Conclusions:
- The zebrafish embryo serves as a powerful, transparent vertebrate model for the in vivo characterization of nanoparticles.
- PEGylation of nanoparticles is a viable strategy to improve their circulation time and reduce non-specific uptake.
- Zebrafish embryo-based screening offers a promising platform for advancing nanoparticle development towards preclinical cancer therapy applications.
