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Caspase-3-Triggered Intracellular Gadolinium Nanoparticle Formation for T 1 -Weighted Magnetic Resonance Imaging of Apoptosis In Vivo .

Hai-Dong XuXiaotong ChengXianbao SunPeiyao ChenWenjun ZhanXiaoyang LiuXinliang WangBing HuGaolin Liang
Published in: Nano letters (2023)
Apoptosis, with a hallmark of upregulated protease Caspase-3, has been frequently imaged with various probes to reveal the therapeutic efficiencies of different drugs. However, activatable molecular probes with programmable self-assembling behaviors that enable enhanced T 1 -weighted magnetic resonance imaging (MRI) of apoptosis remain scarce. Herein, taking advantage of a CBT-Cys click reaction, we rationally designed a Caspase-3-activatable self-assembling probe Ac-Asp-Glu-Val-Asp-Cys(StBu)-Lys(DOTA(Gd))-CBT ( DEVDC S -Gd-CBT ) for apoptosis imaging in vivo . After Caspase-3 cleavage in apoptotic cells, DEVDC S -Gd-CBT underwent CBT-Cys click reaction to form a cyclic dimer, which self-assembled into Gd nanoparticles. With this probe, enhanced T 1 -weighted MR images of apoptosis were achieved at low magnetic fields in vitro , in cis -dichlorodiamineplatinum-induced apoptotic cells and in tail-amputation-simulated apoptotic zebrafish. We anticipate that the smart probe DEVDC S -Gd-CBT could be applied for T 1 -weighted MRI of apoptosis-related diseases in the clinic in the future.
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