Zhenluan Xue

X-ray-Activated Near-Infrared Persistent Luminescent Probe for Deep-Tissue and Renewable in Vivo Bioimaging

Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) are considered as new alternative optical probes due to being free of autofluorescence, benefited from the self-sustained emission after excitation and high signal-to-noise ratio. However, the NIR-emitted PLNPs always present a short decay time and require excitation by ultraviolet or visible light with a short penetrable depth, remarkably hindering their applications for in vivo long-term tracking and imaging. Therefore, it is important to develop NIR-emitted PLNPs with in vivo activation nature by new excitation sources with deeper penetrating depths. Here, we propose a new type of X-ray-activated ZnGa2O4:Cr PLNPs (X-PLNPs) with efficient NIR persistent emission and rechargeable activation features, in which both the excitation and emission possess a high penetrable nature in vivo. These X-PLNPs exhibit long-lasting, up to 6 h, NIR emission at 700 nm after the stoppage of the X-ray excitation source. More importantly, the designed X-PLNPs can be readily reactivated by a soft X-ray excitation source with low excitation power (45 kVp, 0.5 mA) to restore in vivo bioimaging signals even at 20 mm depth. Renewable in vivo whole-body bioimaging was also successfully achieved via intravenous injection/oral administration of X-PLNPs after in situ X-ray activation. This is the first time that NIR-emitted PLNPs have been demonstrated to be recharged by X-ray light for deep-tissue in vivo bioimaging, which paves the way for in vivo renewable bioimaging using PLNPs and makes the PLNPs more competitive in bioimaging area.

Multifunctional BaYbF5: Gd/Er upconversion nanoparticles for in vivo tri-modal upconversion optical, X-ray computed tomography and magnetic resonance imaging

Development of high-quality upconversion nanoparticles (UCNPs) with combination of the merits of multiple molecular imaging techniques, such as, upconversion luminescence (UCL) imaging, X-ray computed tomography (CT), and magnetic resonance (MR) imaging, could significantly improve the accuracy of biological diagnosis. In this work, multifunctional BaYbF5: Gd/Er (50:2mol%) UCNPs were synthesized via a solvothermal method using oleic acid (OA) as surface ligands (denoted as OA-UCNPs). The OA-UCNPs were further treated by diluted HCl to form ligand-free UCNPs (LF-UCNPs) for later bioimaging applications. The cytotoxicity assay in HeLa cells shows low cell toxicity of these LF-UCNPs. Owing to the efficient UCL of BaYbF5: Gd/Er, the LF-UCNPs were successfully used as luminescent bioprobe in UCL bioimaging. And, X-ray CT imaging reveals that BaYbF5: Gd/Er UCNPs can act as potential contrast agents for detection of the liver and spleen in the live mice owing to the high-Z elements (e.g., Ba, Yb, and Gd) in host matrix. Moreover, with the addition of Gd, the as-designed UCNPs exhibit additional positive contrast enhancement in T1-weighted MR imaging. These findings demonstrate that BaYbF5: Gd/Er UCNPs are potential candidates for tri-modal imaging.

M2+ Doping Induced Simultaneous Phase/Size Control and Remarkable Enhanced Upconversion Luminescence of NaLnF4 Probes for Optical-Guided Tiny Tumor Diagnosis

Doping has played a vital role in constructing desirable hybrid materials with tunable functions and properties via incorporating atoms into host matrix. Herein, a simple strategy for simultaneously modifying the phase, size, and upconversion luminescence (UCL) properties of the NaLnF4 (Ln = Y, Yb) nanocrystals by high-temperature coprecipitation through nonequivalent M2+ doping (M = Mg2+ , Co2+ ) has been demonstrated. The phase transformation from cubic to hexagonal is readily achieved by doping M2+ . Compared with Mg-free sample, a remarkable enhancement of overall UCL (≈27.5 times) is obtained by doping Mg2+ . Interestingly, owing to the efficient UCL, red UCL-guided tiny tumor (down to 3 mm) diagnosis is demonstrated for the first time. The results open up a new way of designing high efficient UCL probe with combination of hexagonal phase and small size for tiny tumor detection.

Short-wave near-infrared emissive GdPO4:Nd3+ theranostic probe for in vivo bioimaging beyond 1300 nm

The optical probes working in the second near-infrared (NIR-II) window have attracted increasing research interest for their advantages of high tissue penetration depth, low autofluorescence, and unprecedentedly improved imaging sensitivity and spatial resolution. Therefore, it is of great significance to design a new nanoplatform by integration of NIR-II optical imaging and drug delivery functions. Herein, a multifunctional nanoplatform based on GdPO4:Nd3+ yolk–shell sphere was developed for dual-modal in vivo NIR-II/X-ray bioimaging and pH-responsive drug delivery. The in vivo NIR-II bioimaging and real-time tracking presented that these probes were mainly accumulated in liver and spleen. Moreover, owing to the large X-ray absorption coefficient of Gd3+, these probes are successfully used as superior X-ray imaging agents than iobitridol. The in vivo toxicity assessments demonstrate the low biotoxicity of the GdPO4:Nd3+ spheres in living animals. More importantly, apart from the excellent dual-modal bioimaging, these yolk–shell-structured probes were also used as ideal nanotransducer for pH-responsive drug delivery of doxorubicin (DOX). These findings open up the opportunity of designing theranostic nanoplatform with integration of imaging-based diagnosis and therapy.