Sun Kangjun, Xu Ruitong, Xue Bingyan, Liu Pengfei, Bai Jianan, Tian Ye, Li Xiaolin, Tang Qiyun
Nanjing Medical University, Nanjing, China.
Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Chem. 2023 Feb 8;11:1121957. doi: 10.3389/fchem.2023.1121957. eCollection 2023.
In recent years, organic fluorescent probes with tumor microenvironment (TME)-responsive fluorescence turn-on properties have been increasingly used in imaging-guided tumor resection due to their higher signal-to-noise ratio for tumor imaging compared to non-responsive fluorescent probes. However, although researchers have developed many organic fluorescent nanoprobes responsive to pH, GSH, and other TME, few probes that respond to high levels of reactive oxygen species (ROS) in the TME have been reported in imaging-guided surgery applications. In this work, we prepared Amplex Red (ADHP) with excellent ROS response performance as an ROS-responsive nanoprobe and studied its application in image-guided tumor resection for the first time. To confirm whether the nanoprobe can be used as an effective biological indicator to distinguish tumor sites, we first detected 4T1 cells with the ADHP nanoprobe, demonstrating that the probe can utilize ROS in tumor cells for responsive real-time imaging. Furthermore, we conducted fluorescence imaging in 4T1 tumor-bearing mice, and the ADHP probe can rapidly oxidize to form resorufin in response to ROS, which can effectively reduce the background fluorescence signal compared with the single resorufin probe. Finally, we successfully carried out image-guided surgery of 4T1 abdominal tumors under the guidance of fluorescence signals. This work provides a new idea for developing more TME-responsive fluorescent probes and exploring their application in image-guided surgery.
近年来，具有肿瘤微环境（TME）响应性荧光开启特性的有机荧光探针因其在肿瘤成像中比无响应荧光探针具有更高的信噪比，越来越多地用于成像引导的肿瘤切除。然而，尽管研究人员已经开发出许多对pH、谷胱甘肽和其他TME有响应的有机荧光纳米探针，但在成像引导手术应用中，很少有报道对TME中高水平活性氧（ROS）有响应的探针。在这项工作中，我们制备了具有优异ROS响应性能的Amplex Red（ADHP）作为ROS响应纳米探针，并首次研究了其在图像引导肿瘤切除中的应用。为了确认纳米探针是否可以用作区分肿瘤部位的有效生物指示剂，我们首先用ADHP纳米探针检测了4T1细胞，证明该探针可以利用肿瘤细胞中的ROS进行响应性实时成像。此外，我们在荷4T1肿瘤的小鼠中进行了荧光成像，ADHP探针可以响应ROS迅速氧化形成试卤灵，与单一的试卤灵探针相比，它可以有效降低背景荧光信号。最后，我们在荧光信号引导下成功地对4T1腹部肿瘤进行了图像引导手术。这项工作为开发更多TME响应性荧光探针并探索其在图像引导手术中的应用提供了新思路。
