Authors
Youshi Lin, Zhiyuan Yuan, Xiaogang Liu, Kanyi Pu
Published in
Angewandte Chemie (International ed. in English). Pages e6875075. Oct 10, 2026. Epub Oct 10, 2026.
Abstract
Bioorthogonality-activatable optical imaging activates caged or quenched probes via bioorthogonal reactions for disease diagnosis. Although chemiluminescence enables low-background detection, it has rarely been applied to bioorthogonality-activatable imaging. Here, we synthesize chemiluminescent tetrazine probes (CLTZs) by coupling a tetrazine acceptor to a phenoxy-1,2-dioxetane donor through π-conjugated vinylene linkers, enabling biomarker and bioorthogonality dual-locked activation for cancer urine testing. Unlike conventional chemiluminophores, tetrazine in CLTZs mediates an internal-conversion-to-a-dark-state quenching mechanism, suppressing chemiluminescence even after phenolate formation. Strong chemiluminescence is restored only when the phenolate form undergoes bioorthogonal reaction with bicyclononyne (BCN), generating pyridazine-containing donor-π-acceptor chemiluminophores. This unique dark state enables development of an H2O2 and bioorthogonality dual-locked probe (HBCP), emitting only when both H2O2 and BCN are present. By engineering BCN into a cancer-activatable bioorthogonal urinary reporter (CBUR) that releases renal-clearable BCN in tumors, a chemiluminescent bioorthogonal pair (HBCP & CBUR) is created. This pair achieves in vivo tumor imaging with a signal-to-background ratio of 438 and detects lung metastasis in early urinary assays with up to 23.9-fold signal enhancement over healthy mice. This work provides a molecular design for bioorthogonality-activatable chemiluminescence toward noninvasive, sensitive disease diagnosis.
PMID:
42856089
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.
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