A 5‐Azetidinyl BODIPY–Olaparib Conjugate for PARP‐Targeted Nuclear and Orthotopic Oral Tumor Imaging

Poly(ADP‐ribose) polymerase (PARP) is a clinically validated therapeutic target and an attractive biomarker for fluorescence‐guided tumor imaging. However, the nuclear localization of PARP imposes a stringent requirement on probe design, as fluorophore installation must not compromise nuclear entry of the targeting ligand. Herein, we report a focused series of 5‐azetidinyl BODIPY–olaparib conjugates as PARP‐targeted fluorescent probes. By attaching olaparib‐derived ligands to the 5‐position of the BODIPY core through flexible linkers, we sought to preserve conformational flexibility while introducing a donor–acceptor fluorophore with an enlarged Stokes shift. Among the synthesized probes, 1a exhibited the most favorable cellular imaging performance, showing efficient nuclear localization in PARP‐overexpressing U87 and Cal27 cells. Competitive blocking with olaparib and comparison with HEK293 cells supported PARP‐dependent imaging. In Cal27 xenograft and orthotopic oral tumor models, 1a showed rapid tumor accumulation and clear tumor visualization. It provides a wider range of probe options for intraoperative tracking of oral tumors.