Authors
Wenfang Liang, Liyue Wang, Xuan Wang, Xinran Li, Hao Xing, Lu Sun, Zhen Xi, Long Yi
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e78356. Oct 18, 2026. Epub Oct 18, 2026.
Abstract
Methylselenol (CH3SeH) is not only a key selenium (Se) metabolite but also a potent therapeutic molecule. Chemical tools for stimulus-responsive delivery of CH3SeH should be crucial for exploring Se-related biomedicine. Nevertheless, the classical 1,6-self-immolation is inefficient in releasing the poorly leaving selenol, and donation platforms for triggerable release of the CH3SeH remain lacking. Herein, we report the first general responsive platform (Triggered Donation for MethylSelenol, termed TD-MSe) via fast intramolecular amino-activated methylselenocarbamates (t1/2 = 5 s at pH 7.4), enabling the efficient cyclization release of CH3SeH without electrophilic byproducts. We leverage the caged TD-MSe motifs to successfully create triggered donors that are stable before activation but can liberate CH3SeH under different stimulus conditions in vitro and in live cells. Additionally, we demonstrate that the tumor-associated oxidoreductase (hNQO1)-triggered CH3SeH donor was activated in hNQO1-positive HT-29 cells but not in hNQO1-negative cells. Moreover, we can use the CH3SeH prodrug to selectively kill metastatic cells of hNQO1-overexpressing cancer types, providing a promising therapeutic strategy for difficult-to-treat diseases. We anticipate that the new-release chemistry will be widely applied for developing advanced tools toward smart selenol delivery and therapy.
PMID:
42893486
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.
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