Year: 2017
Type: article
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.
Source: Nature Communications
DOI: 10.1038/ncomms14179
Authors: Michael J. Mitchell, Jamie Webster, Amanda Chung, Pedro P. G. Guimarães, Omar F. Khan, Robert Langer
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Burroughs Wellcome Fund, Prostate Cancer Foundation, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Max-Planck-Gesellschaft, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute
Awards: G2036389291, G2360436881, G3250453925, MIT-Harvard Center of Cancer Nanotechnology Excellence, G4774430914, G5735053113, G6632036768, Polymeric Nanoparticles for siRNA Delivery to Bone Marrow Endothelium to Disrupt Tumor Cell Adhesion and Bone Metastasis Formation In Vivo, G7888124300, Cancer Center Support (Core) Grant
OpenAlex ID: W2601774725
