Alkaline Phosphatase Enabled Fluorogenic Reaction and <i><i>in situ</i></i> Coassembly of Near-Infrared and Radioactive Nanoparticles for <i><i>in vivo</i></i> Imaging

Abstract

Smart near-infrared (NIR) fluorescence (FL) and positron emission tomography (PET) bimodal probes have shown promise for preoperative and intraoperative imaging of tumors. In this paper, we report an enzyme-activatable probe (P-CyFF-⁶⁸Ga) and its cold probe (P-CyFF-Ga) using an enzyme-induced fluorogenic reaction and <i><i>in situ</i></i> coassembly strategy and demonstrate the utility for NIR FL/PET bimodality imaging of enzymatic activity. P-CyFF-⁶⁸Ga and P-CyFF-Ga can be converted into dephosphorylated CyFF-⁶⁸Ga and CyFF-Ga in response to alkaline phosphatase (ALP) and subsequently coassemble into fluorescent and radioactive nanoparticles (NP-⁶⁸Ga). The ALP-triggered <i><i>in situ</i></i> formed NP-⁶⁸Ga is prone to anchoring on the ALP-positive HeLa cell membrane, permitting the concurrent enrichment of NIR FL and radioactivity. The enhancements in NIR FL and radioactivity enables high sensitivity and deep-tissue imaging of ALP activity, consequently facilitating the delineation of HeLa tumor foci from the normal tissues <i><i>in vivo</i></i>.