Harnessing Methylselenol (CH₃SeH): A Highly Effective Platform for Stimuli-Responsive Delivery With Therapeutic Potential.
- 1College of Chemical Engineering and Beijing Key Laboratory of Bioprocess, Beijing University of Chemical Technology, Beijing, China.
- 2Tianjin Key Laboratory On Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
- 3National Pesticide Engineering Research Center (Tianjin), Department of Chemical Biology, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center For New Organic Matter, Nankai University, Tianjin, China.
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.
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BibTeX
@article{liang2026harnessing,
title = {{Harnessing Methylselenol (CH₃SeH): A Highly Effective Platform for Stimuli-Responsive Delivery With Therapeutic Potential.}},
author = {Wenfang Liang and Liyue Wang and Xuan Wang and Xinran Li and Hao Xing and Lu Sun and Zhen Xi and Long Yi},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78356},
url = {https://europepmc.org/article/MED/42893486},
note = {CC BY},
}
RIS
TY - JOUR
TI - Harnessing Methylselenol (CH₃SeH): A Highly Effective Platform for Stimuli-Responsive Delivery With Therapeutic Potential.
AU - Wenfang Liang
AU - Liyue Wang
AU - Xuan Wang
AU - Xinran Li
AU - Hao Xing
AU - Lu Sun
AU - Zhen Xi
AU - Long Yi
PY - 2026
DA - 2026/10/18
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78356
UR - https://europepmc.org/article/MED/42893486
AB - 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.
SN - 2198-3844
ER -