Caspase-3-Triggered Intracellular Gadolinium Nanoparticle Formation for T<sub>1</sub>-Weighted Magnetic Resonance Imaging of Apoptosis <i>In Vivo</i>.
basic_science · Level V
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- Record sourced from PubMed, PMID 37363812.
- Also identified by DOI 10.1021/acs.nanolett.3c01787.
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Abstract
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<sub>1</sub>-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 (<b>DEVDC</b><sub><b>S</b></sub><b>-Gd-CBT</b>) for apoptosis imaging <i>in vivo</i>. After Caspase-3 cleavage in apoptotic cells, <b>DEVDC</b><sub><b>S</b></sub><b>-Gd-CBT</b> underwent CBT-Cys click reaction to form a cyclic dimer, which self-assembled into Gd nanoparticles. With this probe, enhanced T<sub>1</sub>-weighted MR images of apoptosis were achieved at low magnetic fields <i>in vitro</i>, in <i>cis</i>-dichlorodiamineplatinum-induced apoptotic cells and in tail-amputation-simulated apoptotic zebrafish. We anticipate that the smart probe <b>DEVDC</b><sub><b>S</b></sub><b>-Gd-CBT</b> could be applied for T<sub>1</sub>-weighted MRI of apoptosis-related diseases in the clinic in the future.
Medical subject headings
- Gadolinium
- Nanoparticles