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Fluorescence-guided tumor resection with a cathepsin B-activatable, EGFR-targeted probe and a dual-mode surgical exoscope.

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Title: Fluorescence-guided tumor resection with a cathepsin B-activatable, EGFR-targeted probe and a dual-mode surgical exoscope.
Authors: Sung Y; Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Graduate Program in Bioindustrial Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Choi Y; Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Park SM; Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Kyung Hee University, Seoul, 02453, Republic of Korea., Choi N; Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 02841, Republic of Korea; Department of Convergence Medicine, College of Medicine, Korea University, Seoul, 02841, Republic of Korea; Institute of Human Genetics, College of Medicine, Korea University, Seoul, 02841, Republic of Korea; Research Institute for Convergence Biomedical Science, College of Medicine, Korea University, Seoul, 02841, Republic of Korea; Bio-Medical Research Center, Korea University Guro Hospital, Seoul, 08308, Republic of Korea., Lee S; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Kyung Hee University, Seoul, 02453, Republic of Korea., Suh SB; Center for Healthcare Robotics, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Kim C; AI-Robot Department, University of Science and Technology, Seoul, 02792, Republic of Korea; Computational Science Centre, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Hur W; Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea., Cho SW; Graduate Program in Bioindustrial Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea; Center for Nanomedicine, Institute for Basic Science (IBS), Seoul, 03722, Republic of Korea. Electronic address: seungwoocho@yonsei.ac.kr., Lee D; Bionics Research Center, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; Division of AI Robotics, KIST School, University of Science and Technology, Seoul, 02792, Republic of Korea; Yonsei-KIST Convergence Research Institute, Yonsei University, Seoul, 03722, Republic of Korea. Electronic address: dkylee@kist.re.kr., Ryu JH; Medicinal Materials Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea. Electronic address: jhryu@kist.re.kr.
Source: European journal of medicinal chemistry [Eur J Med Chem] 2025 Dec 15; Vol. 300, pp. 118108. Date of Electronic Publication: 2025 Aug 30.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE
Imprint Name(s): Publication: Paris : Editions Scientifiques Elsevier
Original Publication: Paris, S.E.C.T. [etc.]
MeSH Terms: Cathepsin B*/metabolism , ErbB Receptors*/metabolism , ErbB Receptors*/antagonists & inhibitors , Fluorescent Dyes*/chemistry , Fluorescent Dyes*/chemical synthesis , Fluorescent Dyes*/metabolism , Fluorescent Dyes*/pharmacology , Triple Negative Breast Neoplasms*/surgery , Triple Negative Breast Neoplasms*/diagnostic imaging , Triple Negative Breast Neoplasms*/metabolism, Humans ; Animals ; Mice ; Optical Imaging ; Female ; Cetuximab/chemistry ; Cetuximab/pharmacology ; Cell Line, Tumor ; Mice, Nude ; Fluorescence ; Surgery, Computer-Assisted ; Molecular Structure
Abstract: Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Fluorescence-guided surgery enhances surgical precision by enabling real-time tumor visualization. Here, we developed a cathepsin B-activatable imaging probe conjugated to the EGFR-targeting antibody cetuximab (Cetux-CB probe) for fluorescence-guided resection of triple-negative breast cancer (TNBC). The probe consists of a cathepsin B-sensitive peptide linker, a near-infrared fluorophore (Flamma™ Fluors 749), and a quencher (qFlamma Black01), enabling enzymatic activation following tumor-specific accumulation. The Cetux-CB probe exhibited robust cathepsin B-dependent fluorescence activation in EGFR-overexpressing TNBC cells and xenograft tumors, with high tumor accumulation and minimal background in normal tissues. Following systemic administration, the probe demonstrated prolonged and confined fluorescence in vivo, outperforming both non-targeted and always-on fluorescent controls. When combined with a dual-mode surgical exoscope, the probe allowed precise intraoperative tumor localization and guided accurate incision and dissection, confirmed by the absence of residual signal. This study demonstrates the clinical potential of combining dual-responsive imaging probes with compatible imaging systems to improve surgical outcomes in TNBC and other EGFR-positive cancers.
(Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Substance Nomenclature: EC 3.4.22.1 (Cathepsin B)
EC 2.7.10.1 (ErbB Receptors)
0 (Fluorescent Dyes)
EC 2.7.10.1 (EGFR protein, human)
PQX0D8J21J (Cetuximab)
Entry Date(s): Date Created: 20250905 Date Completed: 20251011 Latest Revision: 20251011
Update Code: 20251012
DOI: 10.1016/j.ejmech.2025.118108
PMID: 40911969
Database: MEDLINE
Description
Abstract:Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br />Fluorescence-guided surgery enhances surgical precision by enabling real-time tumor visualization. Here, we developed a cathepsin B-activatable imaging probe conjugated to the EGFR-targeting antibody cetuximab (Cetux-CB probe) for fluorescence-guided resection of triple-negative breast cancer (TNBC). The probe consists of a cathepsin B-sensitive peptide linker, a near-infrared fluorophore (Flamma™ Fluors 749), and a quencher (qFlamma Black01), enabling enzymatic activation following tumor-specific accumulation. The Cetux-CB probe exhibited robust cathepsin B-dependent fluorescence activation in EGFR-overexpressing TNBC cells and xenograft tumors, with high tumor accumulation and minimal background in normal tissues. Following systemic administration, the probe demonstrated prolonged and confined fluorescence in vivo, outperforming both non-targeted and always-on fluorescent controls. When combined with a dual-mode surgical exoscope, the probe allowed precise intraoperative tumor localization and guided accurate incision and dissection, confirmed by the absence of residual signal. This study demonstrates the clinical potential of combining dual-responsive imaging probes with compatible imaging systems to improve surgical outcomes in TNBC and other EGFR-positive cancers.<br /> (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
ISSN:1768-3254
DOI:10.1016/j.ejmech.2025.118108