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.Burroughs Wellcome Fund (Career Award at the Scientific Interface)Ruth L. Kirschstein National Research Service Award (F32CA200351)National Institutes of Health (U.S.)Max Planck Society for the Advancement of Science (Fellowship)Burroughs Wellcome Fund (1015145)Fundação Estudar (Fellowship)National Institutes of Health (U.S.) (Grant U54CA151884)National Institutes of Health (U.S.) (Contract HHSN268201000045C)David H. Koch Institute for Integrative Cancer Research at MIT. Prostate Cancer Foundation Program in Cancer NanotherapeuticsNational Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)David H. Koch Institute for Integrative Cancer Research at MIT. Marble Center for Cancer NanomedicineConselho Nacional de Pesquisas (Brazil) (Postdoctoral Fellowship 202856/2015-1
