Xu Hai-Dong, Sun Xianbao, Huang Zheng, Cheng Xiaotong, Fu Xiancheng, Li Jiayu, Wei Ziwen, Qian Junchao, Liang Gaolin
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China.
State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Road, Nanjing 210023, China.
J Am Chem Soc. 2025 Jul 9;147(27):23923-23930. doi: 10.1021/jacs.5c06634. Epub 2025 Jun 24.
"Assembly-Disassembly" cascade has been utilized as a highly effective approach for tumor theranostics, but its real-time in vivo monitoring remains challenging. Current strategies face a fundamental trade-off between penetration depth and real-time nature, while there is still no report on integrating both features to display this dynamic cascade in a living organism. In this work, we develop a gadolinium (Gd) probe Cys(StBu)-Asp-Asp-Asp-Asp-Lys-Lys(DOTA(Gd))-CBT () to display an in vivo "Assembly-Disassembly" cascade via T-weighted "Off-On-Off" H magnetic resonance imaging (MRI) signals. Under reduction conditions, undergoes a CBT-Cys click reaction to assemble into a Gd nanoparticle, with enhanced H MRI signals of 59.3% and 25.4% in cells and in tumors, respectively ("Off-On"). Upon enterokinase (ENTK) cleavage, the nanoparticle disassembles, rendering decreased H MRI signals of 23.4% and 15.2% in cells and in tumors, respectively ("On-Off"). A scrambled control probe Asp-Asp-Asp-Asp-Lys-Cys(StBu)-Lys(DOTA(Gd))-CBT (), which responds to reduction and ENTK to assemble into a Gd nanoparticle with "Off-On" H MRI signals, is designed and studied in parallel. During 1 h tumor imaging, while only displays "Off-On" H MRI signals, clearly shows "Off-On-Off" signals to reflect the "Assembly-Disassembly" cascade of Gd nanoparticles in tumor. We expect that our strategy of real-time display of in vivo "Assembly-Disassembly" cascade could help people to optimize their nanodrug-based tumor theranostics in the near future.
“组装-拆卸”级联已被用作肿瘤诊疗的一种高效方法，但其体内实时监测仍具有挑战性。当前策略在穿透深度和实时性之间面临基本的权衡，同时仍没有关于整合这两个特征以在活体中展示这种动态级联的报道。在这项工作中，我们开发了一种钆（Gd）探针Cys(StBu)-Asp-Asp-Asp-Asp-Lys-Lys(DOTA(Gd))-CBT（），通过T加权“关闭-开启-关闭”氢磁共振成像（MRI）信号来展示体内“组装-拆卸”级联。在还原条件下，发生CBT-Cys点击反应组装成Gd纳米颗粒，在细胞和肿瘤中的氢MRI信号分别增强了59.3%和25.4%（“关闭-开启”）。经肠激酶（ENTK）切割后，纳米颗粒分解，细胞和肿瘤中的氢MRI信号分别降低了23.4%和15.2%（“开启-关闭”）。同时设计并研究了一种乱序对照探针Asp-Asp-Asp-Asp-Lys-Cys(StBu)-Lys(DOTA(Gd))-CBT（），其对还原和ENTK有反应，通过“关闭-开启”氢MRI信号组装成Gd纳米颗粒。在1小时的肿瘤成像过程中，当仅显示“关闭-开启”氢MRI信号时，清晰地显示出“关闭-开启-关闭”信号，以反映肿瘤中Gd纳米颗粒的“组装-拆卸”级联。我们期望我们实时展示体内“组装-拆卸”级联的策略能够在不久的将来帮助人们优化基于纳米药物的肿瘤诊疗。
