Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids
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Use of multicellular tumor spheroids (MTS) to investigate therapies has gained impetus because they have potential to mimic factors including zonation, hypoxia and drug-resistance. However, analysis remains difficult and often destroys 3D integrity. Here we report an optical technique using targeted nanosensors that allows in situ 3D mapping of redox potential gradients whilst retaining MTS morphology and function. The magnitude of the redox potential gradient can be quantified as a free energy difference (ΔG) and used as a measurement of MTS viability. We found that by delivering different doses of radiotherapy to MTS we could correlate loss of ΔG with increasing therapeutic dose. In addition, we found that resistance to drug therapy was indicated by an increase in ΔG. This robust and reproducible technique allows interrogation of an in vitro tumor-model's bioenergetic response to therapy, indicating its potential as a tool for therapy development.
Jamieson , L E , Camus , V L , Bagnaninchi , P O , Fisher , K M , Stewart , G D , Nailon , W H , McLaren , D B , Harrison , D J & Campbell , C J 2016 , ' Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids ' , Nanoscale , vol. 8 , no. 37 , pp. 16710-16718 . https://doi.org/10.1039/C6NR06031E
Copyright 2016 the Author(s), published by the Royal Society of Chemistry. This Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
DescriptionCJC is grateful to the Leverhulme trust for support (Project Grant RPG-2012-680). VLC is grateful to the Jamie King Cancer Research Fund for funding.
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