Photoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications
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ABSTRACT Companion diagnostics (CDx) are powerful tests that can provide physicians with crucial biomarker information that can improve treatment outcomes by matching therapies to patients.
Here, we report a photoacoustic imaging-based CDx (PACDx) for the selective detection of elevated glutathione (GSH) in a lung cancer model. GSH is abundant in most cells, so we adopted a
physical organic chemistry approach to precisely tune the reactivity to distinguish between normal and pathological states. To evaluate the efficacy of PACDx in vivo, we designed a blind
study where photoacoustic imaging was used to identify mice bearing lung xenografts. We also employed PACDx in orthotopic lung cancer and liver metastasis models to image GSH. In addition,
we designed a matching prodrug, PARx, that uses the same SNAr chemistry to release a chemotherapeutic with an integrated PA readout. Studies demonstrate that PARx can inhibit tumour growth
without off-target toxicity in a lung cancer xenograft model. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS
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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS RAPID IMAGING OF LUNG CANCER USING A RED FLUORESCENT PROBE TO DETECT DIPEPTIDYL PEPTIDASE 4 AND PUROMYCIN-SENSITIVE
AMINOPEPTIDASE ACTIVITIES Article Open access 01 June 2022 COMPARATIVE ONCOLOGY CHEMOSENSITIVITY ASSAY FOR PERSONALIZED MEDICINE USING LOW-COHERENCE DIGITAL HOLOGRAPHY OF DYNAMIC LIGHT
SCATTERING FROM CANCER BIOPSIES Article Open access 08 February 2024 PHOTOACOUSTIC POLYDOPAMINE-INDOCYANINE GREEN (PDA-ICG) NANOPROBE FOR DETECTION OF SENESCENT CELLS Article Open access 27
November 2024 DATA AVAILABILITY All data are available within the Article and its Supplementary Information. Alternatively, data are available upon request from the corresponding author.
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Download references ACKNOWLEDGEMENTS This work was supported by the National Institutes of Health (R35GM133581). M.Y.L acknowledges the Alfred P. Sloan Foundation for financial support.
Major funding for the 500-MHz Bruker CryoProbeTM was provided by the Roy J. Carver Charitable Trust (Muscatine, Iowa; grant no. 15-4521) to the School of Chemical Sciences NMR Lab. The Q-TOF
Ultima mass spectrometer was purchased in part with a grant from the National Science Foundation, Division of Biological Infrastructure (DBI-0100085). We also acknowledge the Core
Facilities at the Carl R. Woese Institute for Genomic Biology for access to the Zeiss LSM 700 confocal microscope and corresponding software. We also acknowledge I. Dobrucka and the
Molecular Imaging Laboratory at the Beckman Institute for use of the IVIS imaging system. M.Y.L. thanks H. Knox for initial animal training and assistance with the NanoZoomer. We thank T.
Bearrood and C. Anorma for assistance with initial confocal imaging experiments, L. Akin for aid with mass spectrometry experiments, S. Anakk and A. Dean for help with interpreting results
from H&E staining experiments, N. Herndon and J. Xu for help with generating the orthotopic lung cancer and liver metastasis models, S. Gardner for providing 4T1 tumour models, J. Sarol
and A. Kaur from Biostatistics, Epidemiology, & Research Design at the Interdisciplinary Health Sciences Institute (UIUC) for aid in statistical analysis, and A. Bennet for helpful
discussions. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Chemistry and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign,
Urbana, IL, USA Melissa Y. Lucero & Jefferson Chan Authors * Melissa Y. Lucero View author publications You can also search for this author inPubMed Google Scholar * Jefferson Chan View
author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS M.Y.L. performed all experiments in this study that include chemical synthesis, in vitro
characterization, cellular studies, tumour model studies, in vivo imaging and sample preparation for ex vivo analysis. J.C. assisted with the blinded animal study. M.Y.L. and J.C. analysed
the data and prepared the manuscript. J.C. conceived the project, with intellectual contributions from M.Y.L. CORRESPONDING AUTHOR Correspondence to Jefferson Chan. ETHICS DECLARATIONS
COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION PEER REVIEW INFORMATION _Nature Chemistry_ thanks Junjie Yao, Deju Ye and the other, anonymous,
reviewer(s) for their contribution to the peer review of this work. PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional
affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION Supplementary Figs. 1–34, Tables 1 and 2 and NMR spectra 2–21. REPORTING SUMMARY RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lucero, M.Y., Chan, J. Photoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications. _Nat.
Chem._ 13, 1248–1256 (2021). https://doi.org/10.1038/s41557-021-00804-0 Download citation * Received: 27 April 2020 * Accepted: 27 August 2021 * Published: 25 October 2021 * Issue Date:
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