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Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis
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 exp...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381511/ https://www.ncbi.nlm.nih.gov/pubmed/32707448 http://dx.doi.org/10.1016/j.ebiom.2020.102902 |
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author | Kocere, Agnese Resseguier, Julien Wohlmann, Jens Skjeldal, Frode Miltzow Khan, Shanawaz Speth, Martin Dal, Nils-Jørgen Knudsen Ng, Matthew Yoke Wui Alonso-Rodriguez, Noelia Scarpa, Edoardo Rizzello, Loris Battaglia, Giuseppe Griffiths, Gareth Fenaroli, Federico |
author_facet | Kocere, Agnese Resseguier, Julien Wohlmann, Jens Skjeldal, Frode Miltzow Khan, Shanawaz Speth, Martin Dal, Nils-Jørgen Knudsen Ng, Matthew Yoke Wui Alonso-Rodriguez, Noelia Scarpa, Edoardo Rizzello, Loris Battaglia, Giuseppe Griffiths, Gareth Fenaroli, Federico |
author_sort | Kocere, Agnese |
collection | PubMed |
description | 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: 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: 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: The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells. FUNDING: We received funding from the Norwegian research council and the Norwegian cancer society |
format | Online Article Text |
id | pubmed-7381511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-73815112020-07-28 Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis Kocere, Agnese Resseguier, Julien Wohlmann, Jens Skjeldal, Frode Miltzow Khan, Shanawaz Speth, Martin Dal, Nils-Jørgen Knudsen Ng, Matthew Yoke Wui Alonso-Rodriguez, Noelia Scarpa, Edoardo Rizzello, Loris Battaglia, Giuseppe Griffiths, Gareth Fenaroli, Federico EBioMedicine Research paper 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: 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: 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: The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells. FUNDING: We received funding from the Norwegian research council and the Norwegian cancer society Elsevier 2020-07-21 /pmc/articles/PMC7381511/ /pubmed/32707448 http://dx.doi.org/10.1016/j.ebiom.2020.102902 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Kocere, Agnese Resseguier, Julien Wohlmann, Jens Skjeldal, Frode Miltzow Khan, Shanawaz Speth, Martin Dal, Nils-Jørgen Knudsen Ng, Matthew Yoke Wui Alonso-Rodriguez, Noelia Scarpa, Edoardo Rizzello, Loris Battaglia, Giuseppe Griffiths, Gareth Fenaroli, Federico Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis |
title | Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis |
title_full | Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis |
title_fullStr | Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis |
title_full_unstemmed | Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis |
title_short | Real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: Localization, toxicity and treatment analysis |
title_sort | real-time imaging of polymersome nanoparticles in zebrafish embryos engrafted with melanoma cancer cells: localization, toxicity and treatment analysis |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381511/ https://www.ncbi.nlm.nih.gov/pubmed/32707448 http://dx.doi.org/10.1016/j.ebiom.2020.102902 |
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