Radioisotope-mimetic molecular afterglow probe for downregulated cancer biomarker imaging

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. Moreover, DROP quickly becomes inactive in healthy liver tissues due to cytochrome P450 enzyme activity, detecting and delineating tumours as small as 1 mm in diameter for complete surgical resection in both murine and rabbit models. Overall, we provide fundamental guidelines to develop radioisotope-mimetic afterglow luminescence probes and highlight the targeting of downregulated biomarkers as a promising approach in cancer theranostics.