AND-gate contrast agents for enhanced fluorescence-guided surgery
Open accessAbstract
Surgical resection of tumours requires precisely locating and defining the margins between lesions and normal tissue. However, this is made difficult by irregular margin borders. Although molecularly targeted optical contrast agents can be used to define tumour margins during surgery in real time, the selectivity of the contrast agents is often limited by the target being expressed in both healthy and tumour tissues. Here, we show that AND-gate optical imaging probes that require the processing of two substrates by multiple tumour-specific enzymes produce a fluorescent signal with significantly improved specificity and sensitivity to tumour tissue. We evaluated the performance of the probes in mouse models of mammary tumours and of metastatic lung cancer, as well as during fluorescence-guided robotic surgery. Imaging probes that rely on multivariate activation to selectively target complex patterns of enzymatic activity should be useful in disease detection, treatment and monitoring.
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Cathepsin activity measured by the 6QC probe showed a modest but significant reduction with CE(20:4)-lipApoE3 or CE(20:4)-lipApoE4 treatment compared to other treatments that minimally induced lipofuscin.
“Cathepsin activity measured by the 6QC probe40 showed a modest but significant reduction with CE(20:4)-lipApoE3 or CE(20:4)-lipApoE4 treatment compared to other treatments that minimally induced lipofuscin (Figure S6G–H).”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [40]
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Guo, J. L., Braun, D., Fitzgerald, G. A., Hsieh, Y.-T., Rougé, L., Litvinchuk, A., Steffek, M., Propson, N. E., Heffner, C. M., Discenza, C., et al. (2025) · Cell · doi:10.1016/j.cell.2024.10.027 · Cited by 91 · see citing works
“Cathepsin activity measured by the 6QC probe 40 showed a modest but significant reduction with CE(20:4)- lipApoE3 or CE(20:4)-lipApoE4 treatment compared with other treatments that minimally induced lipofuscin (Figures S6G and S6H).”
Mc Larney, B. E., Sonay, A. Y., Apfelbaum, E., Mostafa, N., Monette, S., Goerzen, D., Aguirre, N., Exner, R. M., Habjan, C., Isaac, E., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01248-w · Cited by 28 · see citing works
- Authors
- Widen, J. C., Tholen, M., Yim, J. J., Antaris, A., Casey, K. M., Rogalla, S., Klaassen, A., Sorger, J., & Bogyo, M.
- Affiliations
- Stanford Medicine (US)
- Intuitive Surgical (United States) (US)
- Corresponding author
- Bogyo, Matthew
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2020-09-28
- Volume
- 5
- Issue
- 3
- Pages
- 264-277
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC7969380
- OpenAlex
- W3089876537
- Cited by
- 142
- References
- 5
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 23 · 2023: 27 · 2022: 28 · 2021: 26
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Cancer Society (PF-19-105-01-CCE)
- National Science Foundation (DGE-114747)
- U.S. Department of Health & Human Services | National Institutes of Health (R01 EB026285)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- optical contrast agents, fluorescence-guided surgery, tumour margin delineation, imaging agents, mammary tumors, metastatic lung cancer, robotic surgery, metastasis detection
- MeSH terms
- RAW 264.7 Cells, Animals, Cell Line, Contrast Media, Disease Models, Animal, Female, Fluorescence, Fluorescent Dyes, Lung Neoplasms, Male, Mice, Inbred BALB C, Mammary Neoplasms, Animal, Surgery, Computer-Assisted, Mice, Optical Imaging
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