Intracellular self-assembly of Ru(bpy)₃²⁺ nanoparticles enables persistent phosphorescence imaging of tumors

Abstract

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(StBu)-Lys(Ru(bpy)32+)-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.

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

“…[37] Ruthenium(II) tris(bipyridine), that is, Ru(bpy) 3 2+ modified with cysteine (Cys) and 2-cyanobenzothiazole (CBT) via covalent bonds can assemble into nanoparticles for tumor-imaging with persistent phosphorescence. [38] As shown in Figure 3A, Yan and co-workers reported the construction of AIE metallo-organic vesicles assembled from triarylamine carboxylate (TPA-1) and Zn 2+ ions. Zn 2+ acted as a fluorescence turn-on sensor upon binding with TPA-1.…”

“…[ 37 ] Ruthenium(II) tris(bipyridine), that is, Ru(bpy) 3 2+ modified with cysteine (Cys) and 2‐cyanobenzothiazole (CBT) via covalent bonds can assemble into nanoparticles for tumor‐imaging with persistent phosphorescence. [ 38 ]…”

Recent Advances of Persistent Luminescence Nanoparticles in Bioapplications

“…Such molecular architecture combines passively tumor targeting, specific drug releasing and spontaneous afterglow generation, which provides design guidelines for activatable cancer theranostics (Fig. 12) [161][162][163].…”

Biomaterials based on noncovalent interactions of small molecules

“…The tunability and biocompatibility of EISA allow aberrant levels of enzymes to catalyze the accumulation of imaging agents in situ to obtain accurate and precise imaging. Pioneered by Liang et al (2010[ 58 ]), furin-guided CBT condensation initiates self-assembly process to form nanoparticles with dense imaging agents, facilitating MicroPET imaging (Wang et al, 2019[ 78 ]; Liu et al, 2015[ 62 ]), fluorescence (Li et al, 2019[ 55 ]), and phosphorescence imaging (Li et al, 2018[ 51 ]) in different cases. As reported by Liang et al, ALP-instructed self-assembly generates nanofibers for enhanced CT (Zheng et al, 2016[ 119 ]) and MRI (Dong et al, 2017[ 14 ]).…”