title: Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids.
abstract: 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.
authors.affiliation: EaStCHEM, School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK. colin.campbell@ed.ac.uk.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Jamieson
authors.affiliation: EaStCHEM, School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK. colin.campbell@ed.ac.uk.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Camus
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, EH16 4UU, UK.
authors.forename: Pierre O
authors.initials: PO
authors.lastname: Bagnaninchi
authors.affiliation: EaStCHEM, School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK. colin.campbell@ed.ac.uk.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Fisher
authors.affiliation: Academic Urology Group, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Stewart
authors.affiliation: Edinburgh Radiation Research Collaborative, Department of Oncology Physics, Western General Hospital, Edinburgh EH4 2U, UK and School of Engineering, University of Edinburgh, Edinburgh, EH9 3JL, UK.
authors.forename: William H
authors.initials: WH
authors.lastname: Nailon
authors.affiliation: Edinburgh Radiation Research Collaborative, Edinburgh Cancer Centre, Western General Hospital, Edinburgh EH4 2U, UK.
authors.forename: Duncan B
authors.initials: DB
authors.lastname: McLaren
authors.affiliation: School of Medicine, University of St Andrews, KY16 9TF, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.affiliation: EaStCHEM, School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK. colin.campbell@ed.ac.uk.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Campbell
mesh_terms: D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D049329:Nanostructures; D009369:Neoplasms / Q000737:chemistry*; D010084:Oxidation-Reduction; D013059:Spectrum Analysis, Raman; D018874:Spheroids, Cellular / Q000737:chemistry*; D059016:Tumor Microenvironment