Yang Yang, Liu Xiaoyang, Xu Ying, Xing Fan, Yuan Zihan, Chen Yuxuan, Wu Xiaofeng, Wang Cailian, Liang Gaolin
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, 2 Southeast University Road, Nanjing 211189, China.
Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing 210009, China.
Nano Lett. 2025 Mar 12;25(10):3997-4004. doi: 10.1021/acs.nanolett.5c00041. Epub 2025 Mar 3.
Lysosome abnormality closely relates to a variety of diseases; thus, its long-time tracking could benefit accurate disease diagnosis. Current long-time lysosome imaging probes are not biocompatible enough, while compatible peptide-based probes are easily degraded by the abundant proteinases in lysosome. Herein, we rationally design a d-amino acid-containing peptide Cys(StBu)-d-Glu-Lys(coumarin)-d-Glu-CBT (Cou-D/L-CBT) which is subjected to intracellular GSH-initiated CBT-Cys click reaction and assembles into nanotubes in acidic lysosome. experiments showed that, under reduction environment and at pH 4.8, Cou-D/L-CBT assembled into nanotubes with an outer diameter of 156 nm, accompanied by "turn-on" coumarin excimer fluorescence at 550 nm. Cell experiments indicated that while Cou-D/L-CBT provided 29 h of lysosome fluorescence imaging, control probe Cou-L-CBT sustained only 6 h. We expect that our Cou-D/L-CBT could be applied for sensitive diagnosis of lysosome-related diseases in the clinic in the near future.
溶酶体异常与多种疾病密切相关；因此，对其进行长期追踪有助于准确的疾病诊断。目前的长期溶酶体成像探针生物相容性不足，而基于肽的相容性探针容易被溶酶体中丰富的蛋白酶降解。在此，我们合理设计了一种含d-氨基酸的肽Cys(StBu)-d-Glu-Lys(香豆素)-d-Glu-CBT（Cou-D/L-CBT），它会经历细胞内谷胱甘肽引发的CBT-半胱氨酸点击反应，并在酸性溶酶体中组装成纳米管。实验表明，在还原环境和pH 4.8条件下，Cou-D/L-CBT组装成外径为156 nm的纳米管，同时在550 nm处出现“开启”的香豆素准分子荧光。细胞实验表明，Cou-D/L-CBT可提供29小时的溶酶体荧光成像，而对照探针Cou-L-CBT仅持续6小时。我们期望我们的Cou-D/L-CBT在不久的将来能够应用于临床对溶酶体相关疾病的灵敏诊断。
