A Self-Immobilizing Photoacoustic Probe for Ratiometric In Vivo Imaging of Cu(II) in Tumors

Cu(II) ions play a critical role in tumor growth and metastasis, making in vivo high-resolution imaging of Cu(II) crucial for understanding its role in tumor pathophysiology. However, designing suitable molecular probes for this purpose remains challenging. Herein, we report the development of a photoacoustic probe for specific in vivo imaging of Cu(II) in tumors. This probe utilizes β-galactoside as a targeting group and incorporates a unique self-immobilization strategy. Upon β-galactosidase-mediated cleavage, the probe generates a reactive quinone methide intermediate that covalently binds to intracellular proteins, enabling selective tumor accumulation. The probe exhibits a ratiometric photoacoustic response to Cu(II) with high selectivity over that of other biological species. In vitro and in vivo studies demonstrated the efficacy of the probe for Cu(II) imaging in tumors. This research provides valuable insights into the role of Cu(II) in tumorigenesis and may facilitate the development of diagnostic and therapeutic approaches for cancer.