Tang Yufu, Li Yuanyuan, He Chunxu, Wang Zhen, Huang Wei, Fan Quli, Liu Bin
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 1, Singapore, 117585, Singapore.
State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing, 210023, China.
Nat Commun. 2025 Jan 2;16(1):278. doi: 10.1038/s41467-024-55096-y.
Strong background interference signals from normal tissues have significantly compromised the sensitive fluorescence imaging of early disease tissues with exogenous probes in vivo, particularly for sensitive fluorescence imaging of early liver disease due to the liver's significant uptake and accumulation of exogenous nanoprobes, coupled with high tissue autofluorescence and deep tissue depth. As a proof-of-concept study, we herein report a near-infrared-II (NIR-II, 1.0-1.7 μm) light-excited "off-on-off" NIR-II fluorescent probe (NDP). It has near-ideal zero initial probe fluorescence but can turn on its NIR-II fluorescence in liver cancer tissues and then turn off the fluorescence again upon migration from cancer to normal tissues to minimize background interference. Due to its low background, a blind study employing our probes could identify female mice with orthotopic liver tumors with 100% accuracy from mixed subjects of healthy and tumor mice, and implemented sensitive locating of early orthotopic liver tumors with sizes as small as 4 mm. Our NIR-II-excited "off-on-off" probe design concept not only provides a promising molecular design guideline for sensitive imaging of early liver cancer but also could be generalized for sensitive imaging of other early disease lesions.
正常组织产生的强烈背景干扰信号严重影响了在体内使用外源性探针进行早期疾病组织的灵敏荧光成像，特别是对于早期肝脏疾病的灵敏荧光成像而言，由于肝脏对外源性纳米探针的大量摄取和积累，再加上高组织自发荧光和较深的组织深度，情况更是如此。作为一项概念验证研究，我们在此报告一种近红外二区（NIR-II，1.0 - 1.7 μm）光激发的“开-关-开”型近红外二区荧光探针（NDP）。它具有近乎理想的初始探针零荧光，但能在肝癌组织中开启其近红外二区荧光，然后在从癌组织迁移至正常组织时再次关闭荧光，以将背景干扰降至最低。由于其低背景，一项使用我们探针的盲法研究能够从健康小鼠和肿瘤小鼠的混合群体中以100%的准确率识别出原位肝肿瘤的雌性小鼠，并对小至4 mm的早期原位肝肿瘤进行灵敏定位。我们的近红外二区激发的“开-关-开”探针设计理念不仅为早期肝癌的灵敏成像提供了一种有前景的分子设计指导方针，而且还可推广用于其他早期疾病病变的灵敏成像。
