Active-Targeted ICG for Surgical Navigation and Fluorescence-Guided Laparoscopic Photothermal Ablation in Pancreatic Ductal Adenocarcinoma

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Lei Zhou, Manxiong Dai, Jiahao Zhou, Xingyang Zhao, Zixiong Liu, Hao Bu, Yang Zhou, Yan Liao, Hongwen Liu, Wei Cheng, Kang Chen
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy, but there is limited improvement in its treatment. Near-infrared fluorescence (NIRF) imaging could potentially address the clinical challenges of PDAC. Indocyanine green (ICG) has been widely used in clinical practice; however, its short half-life and lack of active targeting greatly limit its application in pancreatic surgery. In this study, the active targeting peptide KTLLPTP (which actively recognizes PDAC cell surface overexpression Plectin-1) was modified to the ICG to create the novel contrast agent ICG-PTP, which actively targets PDAC cells. It was successfully applied to the NIRF imaging of the PDAC orthotopic mice model, achieving an improved tumor signal background ratio (T/N ratio) of 4.28, compared to 2.34 in the free ICG group. Next, Fluorescence-guided excision of subcutaneous/orthotopic PDAC using ICG-PTP was performed, accurately identifying the tumor margin and significantly facilitating resection efficiency. Finally, PDAC metastases were identified, and interventional photothermal ablation (iPTA) was performed under fluorescence laparoscope guidance. ICG-PTP exhibits good biosafety and clinical transitional potential. Thus, they can provide surgeons with efficient real-time tumor information and offer new treatment strategies for metastases. Accordingly, modification of probes for clinical use and adaptation studies of current equipment are the current focus.

Abstract Image

主动靶向ICG在胰腺导管腺癌手术导航和荧光引导下腹腔镜光热消融中的应用
胰腺导管腺癌(PDAC)是一种侵袭性恶性肿瘤,但其治疗进展有限。近红外荧光(NIRF)成像有可能解决PDAC的临床挑战。吲哚菁绿(ICG)已广泛应用于临床;然而,其半衰期短,缺乏主动靶向性,极大地限制了其在胰腺手术中的应用。本研究将活性靶向肽ktlllptp(主动识别PDAC细胞表面过表达的Plectin-1)修饰到ICG上,生成新型造影剂ICG- ptp,其主动靶向PDAC细胞。成功应用于PDAC原位小鼠模型的NIRF成像,肿瘤信号背景比(T/N比)为4.28,而游离ICG组为2.34。接下来,使用ICG-PTP进行荧光引导下皮下/原位PDAC切除,准确识别肿瘤边缘,显著提高切除效率。最后确定PDAC转移灶,在荧光腹腔镜引导下行介入光热消融(iPTA)。ICG-PTP具有良好的生物安全性和临床过渡潜力。因此,它们可以为外科医生提供有效的实时肿瘤信息,并为转移提供新的治疗策略。因此,用于临床使用的探针的改进和现有设备的适应性研究是当前的重点。
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来源期刊
Analytical Chemistry
Analytical Chemistry 化学-分析化学
CiteScore
12.10
自引率
12.20%
发文量
1949
审稿时长
1.4 months
期刊介绍: Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.
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