Molecular crossbreeding-engineered self-calibrating probe with large emission shift for dual near-infrared imaging of therapy-induced senescence.

Therapy-induced senescence, a consequence of prolonged exposure to chemotherapy and radiotherapy, can complicate cancer prognosis. Herein, we developed a novel near-infrared (NIR) ratiometric fluorescence probe, BTE-Gal, designed using a molecular crossbreeding strategy for dual-channel in vivo imaging of therapy-induced senescence. This probe integrates a dual-emission benzothiazole unit onto an NIR hemicyanine scaffold, resulting in triggerable dual emission with minimal spectral overlap upon exposure to β-galactosidase (β-gal), a widely recognized biomarker for senescent cell detection. The significant bathochromic shift (∼80 nm) between the two NIR emission channels enables self-calibrating imaging of β-gal activity with enhanced resolution, facilitating accurate assessment of drug- and ionizing radiation (IR)-induced senescence. Furthermore, in vivo dual-channel NIR imaging using BTE-Gal effectively distinguished the differential susceptibilities of IR-sensitive and IR-resistant tumors to cellular senescence under IR stress. These findings demonstrate that the dual-channel NIR fluorescence probe BTE-Gal represents a valuable tool for monitoring tumor senescence both in tissues and in vivo, holding promise for facilitating personalized therapeutic decision-making through in situ monitoring of tumor senescence.