ArticleAngewandte Chemie (International ed. in English)2024
Senolysis Enabled by Senescent Cell-Sensitive Bioorthogonal Tetrazine Ligation.
Article in Angewandte Chemie (International ed. in English), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 37 citations in OpenAlex.
- Renal-clearable fluorescent probe for early detection of pancreatic cancer in living murine models.Science advances · 2026Article
- Unnatural C6-Substituted d-Galactosides as Attenuated Substrates of Glycosyl Hydrolases.Chembiochem : a European journal of chemical biology · 2026Article
- Red light-responsive bioorthogonal chemistry enabled on-demand prodrug activation for cancer therapy.Acta pharmaceutica Sinica. B · 2026Article
- Achieving cell-type-specific bioorthogonal chemistry using enzyme-activated caged tetrazines.Nature chemical biology · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Exploiting intracellular oncogenic proteins to release cytotoxins.RSC medicinal chemistry · 2026Article
- A Noncovalent Click-to-Release Strategy to Control Bond Cleavage and Prodrug Activation.Angewandte Chemie (International ed. in English) · 2026Article
- Reactive oxygen species-activated bioorthogonal chemistry in living systems enabled by boronate-caged dihydrotetrazines.Nature communications · 2026Article
- Control of Tetrazine Bioorthogonal Reactivity by Rotaxanation.Angewandte Chemie (International ed. in English) · 2025Article
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- Dual-Performing Vinyltetrazine for Rapid, Selective Bioconjugation and Functionalization of Cysteine Proteins.ACS chemical biology · 2025Article
- The Role of Senescence, its Therapeutic Relevance and Clinical Implications in the Tumor Microenvironment.Theranostics · 2025Review
- Senolytic Prodrugs: A Promising Approach to Enhancing Senescence-Targeting Intervention.Chembiochem : a European journal of chemical biology · 2024Review
- Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.Aging and disease · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Although the clearance of senescent cells has been proven to slow down the aging process and promote anti-cancer chemotherapy, the development of senolytics remains challenging. Herein, we report a senolytic strategy enabled by senescent cell-sensitive bioorthogonal tetrazine ligation. Our design is based on linking dihydrotetrazine (Tz) to a galactose (Gal) moiety that serves both as a recognition moiety for senescence-associated β-galactosidase and a caging group for the control of tetrazine activity. Gal-Tz enables efficient click-release of a fluorescent hemicyanine and doxorubicin from a trans-cyclooctene-caged prodrug to detect and eliminate senescent HeLa and A549 cells over non-senescent counterparts with a 16.44 senolytic index. Furthermore, we leverage the strategy for the selective activation and delivery of proteolysis-targeting chimeras (PROTACs) as senolytics. PROTAC prodrug TCO-ARV-771 can be selectively activated by Gal-Tz and delivered into senescent HeLa and A549 cells to induce the degradation of bromodomain-containing protein 4. Senolytic PROTACs may offer an efficient way for intervention on cell senescence thanks to their unique capacity to degrade target proteins in a sub-stoichiometric and catalytic fashion. The results of this study establish the bioorthogonal tetrazine ligation approach as a viable strategy for selective removal of senescent cells.
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Registered trials
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