Luciferase-Loaded\nCalcium Phosphate Nanoparticles\nfor Persistent Bioluminescence Imaging of Orthotopic Breast Tumors

Bioluminescence imaging (BLI) is an important noninvasive\noptical\nimaging technique that has been widely used to monitor many biological\nprocesses due to its high sensitivity, resolution, and signal-to-noise\nratio. However, the BLI technique based on the firefly luciferin-luciferase\nsystem is limited by the expression of exogenous luciferase and the\nshort half-life of firefly luciferin, which pose challenges for long-term\ntracking in vivo. To solve the problems, here we rationally designed\nan intelligent strategy for persistent BLI in tumors by combining\nluciferase-loaded calcium phosphate nanoparticles (Luc@CaP NPs) to\nprovide luciferase and the probe Cys(SEt)-Lys-CBT (CKCBT) to slowly\nproduce the luciferase substrate amino luciferin (Am-luciferin). Luc@CaP\nNPs constructed with CaP as a carrier could enable luciferase activity\nto be maintained in vivo for at least 12 h. And compared to the conventional\nsubstrate luciferin, CKCBT apparently prolonged the BL time by up\nto 2 h through GSH-induced intracellular self-assembly and subsequent\nprotease degradation-induced release of Am-luciferin. We anticipate\nthat this strategy could be applied for clinical translation in more\ndisease diagnosis and treatment in the near future.