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Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis

Author

Listed:
  • Michael J. Mitchell

    (David H. Koch Institute for Integrative Cancer Research, MIT)

  • Jamie Webster

    (David H. Koch Institute for Integrative Cancer Research, MIT)

  • Amanda Chung

    (David H. Koch Institute for Integrative Cancer Research, MIT)

  • Pedro P. G. Guimarães

    (David H. Koch Institute for Integrative Cancer Research, MIT)

  • Omar F. Khan

    (David H. Koch Institute for Integrative Cancer Research, MIT)

  • Robert Langer

    (David H. Koch Institute for Integrative Cancer Research, MIT)

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.

Suggested Citation

  • Michael J. Mitchell & Jamie Webster & Amanda Chung & Pedro P. G. Guimarães & Omar F. Khan & Robert Langer, 2017. "Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14179
    DOI: 10.1038/ncomms14179
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