Synthesis and properties of AIE-active Triazaborolopyridiniums toward fluorescent nanoparticles for cellular imaging and their biodistribution in vivo and ex vivo

Abstract

Three new aggregation-induced emission (AIE) molecules have been prepared by incorporation of the tetraphenylethylene (TPE) unit to the triazaborolopyridinium (TBP). The compounds exhibit broad absorption from 470 to 510 nm and emission from 530 to 600 nm in various solvents. The TPE-linked TBP, TT-1, and the compound with a phenylene bridge, TT-2, demonstrated high fluorescence quantum yields and solvent-sensitive behaviors due to twisted intramolecular charge transfer (TICT). In contrast, the derivative with a thiophene bridge, TT-3, showed less solvent dependence and low fluorescence quantum yield. The presence of a thiophene moiety led to redshift in the absorption and emission spectra due to a lower energy gap, confirmed by cyclic voltammetry (CV) and density functional theory (DFT) calculations. All derivatives displayed AIE in THF-water mixtures at water contents higher than 80% v/v. TT-1 was encapsulated within phospholipid-connected polyethylene glycol (DSPE-PEG) by nanoprecipitation, yielding fluorescent nanoparticles with the average sizes of 80.7–83.7 nm. In cell imaging experiments, the resulting TT-1@DSPE-PEG nanoparticles (NPs) showed no toxicity to H1299 lung carcinoma cells at concentrations up to 50 μM and were successfully internalized by the cells after 2 h incubation. Finally, the biodistribution of TT-1@DSPE-PEG NPs was studied in a bladder cancer murine model. In vivo and ex vivo images indicated that the NPs were highly localized in the stomach of the mouse after 2 h post-injection and showed a small uptake by the tumor after 4 h post-injection.