Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis
Name
Polymeric mechanical.pdf
Size
3.86 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Mitchell, Michael J
Webster, Jamie
Chung, Amanda T
Guimaraes, Pedro P G
Khan, Omar Fizal
Langer, Robert S
Date Issued
March 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Mitchell, Michael J. et al. “Polymeric Mechanical Amplifiers of Immune Cytokine-Mediated Apoptosis.” Nature Communications 8 (2017): 14179.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/ncomms14179
