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 LiangPublished 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.
Keyphrases
- cell death
- cell cycle arrest
- contrast enhanced
- induced apoptosis
- magnetic resonance imaging
- endoplasmic reticulum stress
- oxidative stress
- magnetic resonance
- pi k akt
- living cells
- computed tomography
- fluorescence imaging
- quantum dots
- diffusion weighted imaging
- signaling pathway
- primary care
- network analysis
- single molecule
- high glucose
- dna methylation
- anti inflammatory
- endothelial cells
- pet imaging
- positron emission tomography
- stress induced
- dna binding