Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

作者：Youbin Ding, Runhua Zhou, Guangwei Shi, Yuke Jiang, Zhifen Li, Xiaolong Xu, Jingbo Ma, Jingnan Huang, Chunjin Fu, Hongchao Zhou, Huifang Wang, Jiexuan Li, Zhiyu Dong, Qingling Yu, Kexin Jiang, Yehai An, Yawei Liu, Yilei Li, Le Yu, Zhijie Li, Xiaodong Zhang, Jigang Wang · 发表于：Biomaterials Research · 年份：2024 · DOI：10.34133/bmr.0041 · 被引用次数：18 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Toxin Mechanisms and Immunotoxins、Immunotherapy and Immune Responses

Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17...