• Abstract Molecular afterglow imaging is a biomedical modality with high sensitivity and specificity. • However, due to the short half-lives of existing afterglow agents, longitudinal imaging often requires multiple on-site reinductions. • Here we report a probe with month-long afterglow luminescence and the ability to target a downregulated liver tumour biomarker. • This downregulated-biomarker-activatable afterglow probe (DROP) operates through a self-sustainable photoenergy cycling reaction, during which afterglow resonance energy transfer re-excites the afterglow initiator to regenerate singlet oxygen. • This process initiates new afterglow resonance energy transfer cycles, extending the afterglow duration to over 40 days. • The long afterglow of DROP enables in vivo imaging over 8 h with a single light preinduction, mimicking the imaging process of radioisotopes.
Article Summaries:
- A new molecular afterglow probe, termed DROP, demonstrates month‑long luminescence that can be activated by a downregulated liver‑tumor biomarker. The probe uses a self‑sustaining photo‑energy cycle that repeatedly re‑excites the afterglow initiator, generating singlet oxygen and extending emission beyond 40 days. With a single light pre‑induction, DROP enables continuous in‑vivo imaging for over 8 hours, mimicking the temporal profile of radioisotopes. In healthy liver tissue, the probe rapidly deactivates via cytochrome‑P450 activity, allowing selective tumor delineation of lesions as small as 1 mm in mouse and rabbit models. The study offers design principles for radioisotope‑mimetic afterglow agents and highlights targeting downregulated biomarkers as a promising strategy for cancer theranostics.
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