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This work develops SeCF3-IRD800, a small-molecule HDAC6-targeted NIR-II fluorescent probe designed for precise fluorescence-guided surgery, as well as imaging under diverse pathological backgrounds. The probe shows biocompatibility, effective in vivo tumor imaging within 8 hours, high tumor-to-background contrast, and kidney-dominant metabolism, enabling identification of sub-visible lesions and HDAC6-positive clinical 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reported?",{"text":121,"@type":113},"In vivo validation showed optimal imaging within 8 hours with strong tumor fluorescence and a high tumor-to-background ratio, supporting HDAC6-specific targeting and feasible fluorescence-guided detection of small 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Chu Tang,e,h En Lin,a,b,h Xiaohua Jia,b,c,h Ganyuan Xie,a Peiping Li,a Decheng Li,a Qiyue Yang,f Xiaoyong Guo,b,g Caiguang Cao,b,c Xiaojing Shi,b,c Baojia Zou,a Chaonong Cai,a Jie Tian,b,c,d,e,h,∗ Zhenhua Hu,b,c,h,∗∗ and Jian Lia,h,∗∗∗  \naDepartment of Hepatobiliary Surgery and Liver Transplantation, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China  \nbCAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China  \ncSchool of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, 100049, China  \ndBeijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, 100191, China  \neEngineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, 710071, China  \nfKey Laboratory of Digital Hepatobiliary Surgery, PLA, Institute of Hepatobiliary Surgery of Chinese PLA, Beijing, 100048, China gClinical College of Armed Police General Hospital of Anhui Medical University, Department of Gastroenterology of The Third Medical Center of Chinese PLA General Hospital, Beijing, 100039, China  \nSummary  \nBackground Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and ranks third in terms of both mortality and incidence rates. Surgical resection holds potential as a curative approach for HCC. However, the residual disease contributes to a high 5-year recurrence rate of 70% . Due to their excellent specificity and optical properties, fluorescence-targeted probes are deemed effective auxiliary tools for addressing residual lesions, enabling precise surgical diagnosis and treatment. Research indicates histone deacetylase 6 (HDAC6) overexpression in HCC cells, making it a potential imaging biomarker. This study designed a targeted smallmolecule fluorescent probe, SeCF3-IRDye800cw (SeCF3-IRD800), operating within the Second near-infrared window (NIR-II, 1000–1700 nm) . The study confirms the biocompatibility of SeCF3-IRD800 and proceeds to demonstrate its applications in imaging in vivo, fluorescence-guided surgery (FGS) for liver cancer, liver fibrosis imaging, and clinical samples incubation, thereby preliminarily validating its utility in liver cancer.  \nMethods SeCF3-IRD800 was synthesized by combining the near-infrared fluorescent dye IRDye800cw-NHS with an improved HDAC6 inhibitor. Initially, a HepG2-Luc subcutaneous tumor model (n = 12) was constructed to investigate the metabolic differences between SeCF3-IRD800 and ICG in vivo. Subsequently, HepG2-Luc (n = 12) and HCCLM3-Luc (n = 6) subcutaneous xenograft mouse models were used to assess in vivo targeting by SeCF3-IRD800 . The HepG2-Luc orthotopic liver cancer model (n = 6) was employed to showcase the application of SeCF3-IRD800 in FGS. Liver fibrosis (n = 6) and HepG2-Luc orthotopic (n = 6) model imaging results were used to evaluate the impact of different pathological backgrounds on SeCF3-IRD800 imaging. Three groups of fresh HCC and normal liver samples from patients with liver cancer were utilized for SeCF3-IRD800 incubation ex vivo, while preclinical experiments illustrated its potential for clinical application.  \nFindings The HDAC6 inhibitor 6 (SeCF3) modified with trifluoromethyl was labeled with IRDy800CW-NHS to synthesize the small-molecule targeted probe SeCF3-IRD800, with NIR-II fluorescence signals. SeCF3-IRD800 was rapidly metabolized by the kidneys and exhibited excellent biocompatibility. In vivo validation demonstrated that SeCF3-IRD800 achieved optimal imaging within 8 h, displaying high tumor fluorescence intensity (7658.41 ± 933.34) and high tumor-to-background ratio (5.20 ± 1.04) . Imaging experiments with various expression levels revealed","cbCaick2z57dDPOA","https://ap.wps.com/l/cbCaick2z57dDPOA","pdf",4110187,18,"English","# Summary\n## Background\n## Methods\n## Findings\n## Interpretation","[{\"question\":\"What problem does the study address in liver cancer surgery?\",\"answer\":\"It targets the high recurrence risk after resection by improving auxiliary detection of residual lesions during surgery using fluorescence-guided approaches.\"},{\"question\":\"How was the SeCF3-IRD800 probe designed and synthesized?\",\"answer\":\"SeCF3-IRD800 was synthesized by labeling an HDAC6 inhibitor modified with a trifluoromethyl group using IRDye800CW-NHS, producing an NIR-II fluorescent small molecule.\"},{\"question\":\"What imaging performance and key outcomes were reported?\",\"answer\":\"In vivo validation showed optimal imaging within 8 hours with strong tumor fluorescence and a high tumor-to-background ratio, supporting HDAC6-specific targeting and feasible fluorescence-guided detection of small lesions.\"}]","NIR-II fluorescence-guided liver cancer surgery by a small molecular HDAC6 targeting probe | PDF",1790247744,45]