Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis.
Administration, Intravenous
Animals
Carbocyanines
/ chemistry
Cell Line, Tumor
Doxorubicin
/ administration & dosage
Humans
Macrophages
/ chemistry
Melanoma, Experimental
/ chemistry
Mice
Microscopy, Electron
Nanoparticles
Neoplasm Transplantation
Neural Tube
/ chemistry
Neutrophils
/ chemistry
Polyethylene Glycols
/ chemistry
Polymethacrylic Acids
/ administration & dosage
Skin Neoplasms
/ chemistry
Treatment Outcome
Zebrafish
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
04
01
2020
revised:
29
06
2020
accepted:
03
07
2020
pubmed:
25
7
2020
medline:
8
6
2021
entrez:
25
7
2020
Statut:
ppublish
Résumé
The developing zebrafish is an emerging tool in nanomedicine, allowing non-invasive live imaging of the whole animal at higher resolution than is possible in the more commonly used mouse models. In addition, several transgenic fish lines are available endowed with selected cell types expressing fluorescent proteins; this allows nanoparticles to be visualized together with host cells. Here, we introduce the zebrafish neural tube as a robust injection site for cancer cells, excellently suited for high resolution imaging. We use light and electron microscopy to evaluate cancer growth and to follow the fate of intravenously injected nanoparticles. Fluorescently labelled mouse melanoma B16 cells, when injected into this structure proliferated rapidly and stimulated angiogenesis of new vessels. In addition, macrophages, but not neutrophils, selectively accumulated in the tumour region. When injected intravenously, nanoparticles made of Cy5-labelled poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-PDPA) selectively accumulated in the neural tube cancer region and were seen in individual cancer cells and tumour associated macrophages. Moreover, when doxorubicin was released from PEG-PDPA, in a pH dependant manner, these nanoparticles could strongly reduce toxicity and improve the treatment outcome compared to the free drug in zebrafish xenotransplanted with mouse melanoma B16 or human derived melanoma cells. The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells. We received funding from the Norwegian research council and the Norwegian cancer society.
Sections du résumé
BACKGROUND
BACKGROUND
The developing zebrafish is an emerging tool in nanomedicine, allowing non-invasive live imaging of the whole animal at higher resolution than is possible in the more commonly used mouse models. In addition, several transgenic fish lines are available endowed with selected cell types expressing fluorescent proteins; this allows nanoparticles to be visualized together with host cells.
METHODS
METHODS
Here, we introduce the zebrafish neural tube as a robust injection site for cancer cells, excellently suited for high resolution imaging. We use light and electron microscopy to evaluate cancer growth and to follow the fate of intravenously injected nanoparticles.
FINDINGS
RESULTS
Fluorescently labelled mouse melanoma B16 cells, when injected into this structure proliferated rapidly and stimulated angiogenesis of new vessels. In addition, macrophages, but not neutrophils, selectively accumulated in the tumour region. When injected intravenously, nanoparticles made of Cy5-labelled poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-PDPA) selectively accumulated in the neural tube cancer region and were seen in individual cancer cells and tumour associated macrophages. Moreover, when doxorubicin was released from PEG-PDPA, in a pH dependant manner, these nanoparticles could strongly reduce toxicity and improve the treatment outcome compared to the free drug in zebrafish xenotransplanted with mouse melanoma B16 or human derived melanoma cells.
INTERPRETATION
CONCLUSIONS
The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells.
FUNDING
BACKGROUND
We received funding from the Norwegian research council and the Norwegian cancer society.
Identifiants
pubmed: 32707448
pii: S2352-3964(20)30277-2
doi: 10.1016/j.ebiom.2020.102902
pmc: PMC7381511
pii:
doi:
Substances chimiques
Carbocyanines
0
Polymethacrylic Acids
0
cyanine dye 5
0
poly(2-(diisopropylamino)ethyl methacrylate)
0
Polyethylene Glycols
3WJQ0SDW1A
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102902Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
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