Dual-Activator Codoped Upconversion Nanoprobe with Core–Multishell Structure for in Vitro and in Vivo Detection of Hydroxyl Radical

Monitoring the fluctuation of hydroxyl radical (·OH) in the body can serve as an effective tool for the prediction of relative diseases; however, it is highly challenging due to the radical’s short lifetime, high reactivity, and extremely low concentration. Sandwich structured lanthanide-doped upconversion nanoparticles (UCNPs) exhibit unique luminescence properties and great prospects in bioimaging. Nonetheless, their rather low luminescence efficiency and intensity are serious limitations for their application. Herein, we report on dual-activator codoped UCNPs with a core–multishell structure that greatly improve the luminescence intensity and lifetime by 46-fold and 2.6-fold, respectively, compared to those of the monoactivator doped sandwich structured UCNPs. Moreover, emitting ions in the designed core–multishell (CMS)-UCNPs were confined in a homogeneous and thin shell layer (∼2 nm); thus, the luminescence resonance energy transfer (LRET)-based CMS-UCNPs@azo dye nanoprobe exhibited a largely shortened energy transfer distance and a pronounced luminescence quenching yield (97%), affording the nearly zero background signal and achieving an ultrahigh sensitivity for the detection of ·OH (with limit of quantitation (LOQ) of 0.10 fM). With good biocompatibility, low biotoxicity, and enhanced luminescence intensity and lifetime, the developed nanoprobe was competent in monitoring the subtle fluctuation of ·OH concentration both in vitro and in vivo.