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Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis
Physical forces affect tumour growth, progression and metastasis. Here, we develop polymeric mechanical amplifiers that exploit in vitro and in vivo physical forces to increase immune cytokine-mediated tumour cell apoptosis. Mechanical amplifiers, consisting of biodegradable polymeric particles teth...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364380/ https://www.ncbi.nlm.nih.gov/pubmed/28317839 http://dx.doi.org/10.1038/ncomms14179 |
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author | Mitchell, Michael J. Webster, Jamie Chung, Amanda Guimarães, Pedro P. G. Khan, Omar F. Langer, Robert |
author_facet | Mitchell, Michael J. Webster, Jamie Chung, Amanda Guimarães, Pedro P. G. Khan, Omar F. Langer, Robert |
author_sort | Mitchell, Michael J. |
collection | PubMed |
description | Physical forces affect tumour growth, progression and metastasis. Here, we develop polymeric mechanical amplifiers that exploit in vitro and in vivo physical forces to increase immune cytokine-mediated tumour cell apoptosis. Mechanical amplifiers, consisting of biodegradable polymeric particles tethered to the tumour cell surface via polyethylene glycol linkers, increase the apoptotic effect of an immune cytokine on tumour cells under fluid shear exposure by as much as 50% compared with treatment under static conditions. We show that targeted polymeric particles delivered to tumour cells in vivo amplify the apoptotic effect of a subsequent treatment of immune cytokine, reduce circulating tumour cells in blood and overall tumour cell burden by over 90% and reduce solid tumour growth in combination with the antioxidant resveratrol. The work introduces a potentially new application for a broad range of micro- and nanoparticles to maximize receptor-mediated signalling and function in the presence of physical forces. |
format | Online Article Text |
id | pubmed-5364380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53643802017-04-11 Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis Mitchell, Michael J. Webster, Jamie Chung, Amanda Guimarães, Pedro P. G. Khan, Omar F. Langer, Robert Nat Commun Article Physical forces affect tumour growth, progression and metastasis. Here, we develop polymeric mechanical amplifiers that exploit in vitro and in vivo physical forces to increase immune cytokine-mediated tumour cell apoptosis. Mechanical amplifiers, consisting of biodegradable polymeric particles tethered to the tumour cell surface via polyethylene glycol linkers, increase the apoptotic effect of an immune cytokine on tumour cells under fluid shear exposure by as much as 50% compared with treatment under static conditions. We show that targeted polymeric particles delivered to tumour cells in vivo amplify the apoptotic effect of a subsequent treatment of immune cytokine, reduce circulating tumour cells in blood and overall tumour cell burden by over 90% and reduce solid tumour growth in combination with the antioxidant resveratrol. The work introduces a potentially new application for a broad range of micro- and nanoparticles to maximize receptor-mediated signalling and function in the presence of physical forces. Nature Publishing Group 2017-03-20 /pmc/articles/PMC5364380/ /pubmed/28317839 http://dx.doi.org/10.1038/ncomms14179 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Mitchell, Michael J. Webster, Jamie Chung, Amanda Guimarães, Pedro P. G. Khan, Omar F. Langer, Robert Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
title | Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
title_full | Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
title_fullStr | Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
title_full_unstemmed | Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
title_short | Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
title_sort | polymeric mechanical amplifiers of immune cytokine-mediated apoptosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364380/ https://www.ncbi.nlm.nih.gov/pubmed/28317839 http://dx.doi.org/10.1038/ncomms14179 |
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