Engineering of Reversible Luminescent Probes for Real-time Intravital Imaging of Liver Injury and Repair

Abstract

As the primary organ for drug metabolism and detoxification, the liver is prone to be damaged and its functionality is severely impaired. The treatment of liver diseases is based on a clear understanding of the process underlying liver injury and repair. However, intravital real-time imaging of liver injury and repair is still limited due to the lack of in vivo reversible visualization methods. To this end, we proposed a rational design strategy for the development of reversible upconversion luminescence nanoprobe that allows real-time and in vivo imaging of liver injury and repair processes. As a proof of demonstration, we first developed a small molecule probe NB3 which can reversibly respond to related analytes of early liver injury (peroxynitrite, ONOO-) and liver repair (glutathione, GSH). The small molecule probe was then integrated with a core-shell upconversion nanoparticle to form a sophisticated nanoprobe. Compared to traditional small molecule probes, this nanoprobe exhibited higher selectivity to ONOO − , longer retention time in liver, and a wider response dynamic range to GSH after oxidized by ONOO -. The novel nanoprobe facilitated the successful monitoring and discrimination among the different degrees of liver injury and repair in a mouse model.

Energy Pumping by Surface Collectors on Upconversion Nanoparticles for Extended Transfer and Efficient Self-Evaluable Photodynamic Therapy

“…The multiplex upconversion emissions and relatively low background make upconversion nanoparticle (UCNP) a popular nanomaterial for designing bioprobes in bioanalysis and cancer therapy recently [1][2][3][4][5][6] . Taking UCNP as energy donor and dye attached on its surface as energy acceptor, different "off-on" upconversion bioprobes have been designed for sensing of small molecules such as metal ions 7,8 , ATP 9 , free radicals 10,11 , pH 12,13 , sulfur compounds 14 , and drug metabolites 15,16 . In these sensing strategies the energy acceptors act as target recognition domain, and are needed to keep as close as possible to the emitter inside UCNP for obtaining satisfactory luminescence resonance energy transfer (LRET) efficiency.…”

Dual-Stimulus Responsive Near-Infrared Reversible Ratiometric Fluorescent and Photoacoustic Probe for In Vivo Tumor Imaging

“…Many techniques, such as magnetic resonance imaging, computed tomography, and ultrasonography, have recently been used for imaging and diagnosing tumors. − However, these techniques lack sufficient specificity and sensitivity . In comparison, fluorescent probe-based molecular imaging has a greater potential in accurate imaging of a tumor due to its high sensitivity and high spatial and temporal resolution. − …”