Intracellular self-assembly of Ru(bpy) nanoparticles enables persistent phosphorescence imaging of tumors

Nanoprobes are advantageous over small molecular probes in sensitivity but most luminescence molecules used to construct nanoprobes often suffer from an aggregation-caused quenching effect. Herein, we rationally designed a small molecular probe Cys(S t Bu)-Lys(Ru(bpy) 3 2+ )-CBT ( 1 ) which "smartly" self-assembled into nanoparticles 1-NPs inside cells with non-quenched, persistent phosphorescence. Employing this property, we successfully applied 1 for long-term sensing of biothiol activity in living HepG2 cells and tumors. We envision that, by modifying the amino group with an enzyme substrate, our probe 1 could be further developed for sensing intracellular enzyme activity with non-quenched, persistent phosphorescence. The small molecular Ru(bpy) 3 2+ -derivative probe 1 was rationally designed for intracellular self-assembly of 1-NPs for tumor imaging with persistent phosphorescence.