Songjun Zeng

PEG modified BaGdF5:Yb/Er nanoprobes for multi-modal upconversion fluorescent, in vivo X-ray computed tomography and biomagnetic imaging

Herein, a multi-functional nanoprobe of polyethylene glycol (PEG) modified BaGdF₅:Yb/Er upconversion nanoparticles (UCNPs) for tri-modal bioimaging of fluorescence, computed X-ray tomography (CT), and magnetic application is demonstrated for the first time. The PEG-modified BaGdF₅:Yb/Er UCNPs with optimal small size were synthesized by a facile one-pot hydrothermal method. The as-designed single-phase nanoprobe presents near-infrared to visible upconversion emissions in UC fluorescent bioimaging of HeLa cell. Importantly, we have demonstrated in vivo CT images with enhanced signals of spleen of a mouse for 2 h, indicating the UCNPs can be successfully used as CT contrast agent for improving the detection of splenic diseases. In addition, these UCNPs also exhibit excellent intrinsic paramagnetic property which can be also for magnetic imaging. Therefore, our results indicate that a tri-modal nanoprobe served as fluorescent/CT/magnetic bioimaging can be realized using the PEG-modified BaGdF₅:Yb/Er UCNPs with very low cytotoxicity and long circulation time, which would be very useful in a variety of biomedical application fields.

Bi-functional NaLuF4:Gd3+/Yb3+/Tm3+ nanocrystals: structure controlled synthesis, near-infrared upconversion emission and tunable magnetic properties

In this paper, fluorescent and magnetic bi-functional NaLuF4:Ln (Ln = Gd3+, Yb3+, Tm3+) nanocrystals were synthesized via a simple hydrothermal method using oleic acid as capping ligand. The crystal phase, size, upconversion (UC) properties, and magnetization of the nanocrystals can be readily modified by doping with Gd3+. The results reveal that Gd3+ addition can promote the transformation from the cubic to the hexagonal phase and reduce the size. In addition, NaLuF4:Ln (Ln = Gd3+, Yb3+, Tm3+) nanocrystals present efficient near infrared (NIR) to NIR emission, which is beneficial for in vivo biomedical applications due to the increased penetration depth and low radiation damage of NIR light in bio-tissues. More importantly, owing to the large magnetic moment of Gd3+, the Gd3+-doped NaLuF4 nanocrystals also present excellent paramagnetic properties at room temperature. Therefore, it is expected that these nanocrystals can be used as promising dual-modal nanoprobes for optical bioimaging and magnetic resonance imaging (MRI), and may have potential applications in bioseparation.

Dual-modal upconversion fluorescent/X-ray imaging using ligand-free hexagonal phase NaLuF4:Gd/Yb/Er nanorods for blood vessel visualization

Visualization of blood vessel of lung can improve the detection of the lung and pulmonary vascular diseases. However, research on visualization of blood vessel of lung using the new generation upconversion nanoprobes is still scarce. Herein, high quality hexagonal phase NaLuF4:Gd/Yb/Er nanorods were synthesized by a simple hydrothermal method through doping Gd(3+). Doping Gd can not only promote the phase transformation from cubic to hexagonal and the shape evolution from microtube to rod-like, but also provide an additional magnetic properties for biomedical application. The as-prepared nanorods were further converted to water solubility by treating with HCl for eliminating the capped oleic acid. The ligand-free nanorods were successfully used for high-contrast upconversion fluorescent bioimaging of HeLa cells. Moreover, the in vivo synergistic upconversion fluorescent and X-ray imaging of nude mice were demonstrated by subcutaneously and intravenously administrated the ligand-free nanorods. The X-ray signals were matched well with the upconversion signal, indicating the successfully synergistic bioimaging. The ex-vivo X-ray and upconversion fluorescent imaging of various organs revealed that the nanorods were mainly accumulated in liver and lung. More importantly, the blood vessel of the lung can be readily visualized when these ligand-free nanorods are intravenously injected. Apart from the synergistic X-ray and upconversion bioimaging, the ligand-free nanorods can also possess excellent paramagnetic property for potential magnetic resonance imaging contrast agent. Our results have demonstrated the enhanced visualization of blood vessel of lung performed by dual-modal bioimaging of X-ray and upconversion fluorescence, revealing the great promise of these nanoprobes in angiography imaging. Such a new technique enables the integration of the two bioimaging techniques by combining their collective strengths and minimizing their shortcomings.

Dual-modal fluorescent/magnetic bioprobes based on small sized upconversion nanoparticles of amine-functionalized BaGdF5:Yb/Er

A new type of BaGdF(5):Yb/Er nanoprobe for dual-modal fluorescent and magnetic resonance imaging (MRI) is demonstrated. Water soluble and amine-functionalized BaGdF(5):Yb/Er nanoparticles (NPs) with average size of about 10 nm were synthesized by a facile one-pot hydrothermal method. The in vitro up-converted emission of BaGdF(5):Yb/Er NPs is observed in HeLa cells with near-infrared excitation at 980 nm and served as a fluorescent label. In addition, the cytotoxicity assay in HeLa cells shows low cell toxicity of the amine-functionalized BaGdF(5):Yb/Er NPs. Moreover, these BaGdF(5) NPs exhibit excellent intrinsic paramagnetic properties and enhanced T(1)-weighted MRI images with increased concentrations of BaGdF(5) NPs. Therefore, these results suggest that the amine-functionalized BaGdF(5) NPs with an optimized size and low cell toxicity are promising dual-modal bioprobes for optical bioimaging and MRI.

Synergistic dual-modality in vivo upconversion luminescence/X-ray imaging and tracking of amine-functionalized NaYbF(4):Er nanoprobes.

In this work, the amine-functionalized NaYbF4:Er nanoparticles were developed as dual-modal nanoprobes for synergistic upconversion (UC) luminescence and X-ray imaging in a single system by a simple one-step method of simultaneous synthesis and surface modification. The water-soluble NaYbF4:Er nanoparticles present excellent green and dominant red UC emissions. The in vitro cell imaging shows that the high-contrast green and intense red UC emissions can be observed from HeLa cells treated with these nanoparticles, indicating the successful labeling of HeLa cells. Moreover, the localized spectra measured from HeLa cells and background presented significant green and dominant red UC emissions with the absence of any autofluorescence, further verifying that these nanoparticles can be successfully used as ideal probes for optical UC bioimaging with high contrast and non-autofluorescence. In addition, the amine-functionalized NaYbF4:Er nanoparticles maintained low cell toxicity in HeLa cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. More importantly, these amine-functionalized NaYbF4:Er nanoparticles can also be used as X-ray imaging, owing to the large X-ray absorption efficiency of the Yb ion. The synergistic in vivo UC and X-ray imaging present significant UC luminescence and X-ray signals in the same region of a nude mouse, and the two signals are matched very well, which provides direct evidence for simultaneous UC luminescence and X-ray imaging in a single compound of lanthanide-doped material. Moreover, ex vivo UC imaging shows that these nanoparticles are first accumulated in the lung and gradually translocated from the lung into the liver. These results demonstrate that the amine-functionalized NaYbF4:Er nanoparticles presented here are very attractive nanoprobes for dual-modal UC luminescence and X-ray imaging with low cytotoxicity, autofluorescence free, and synergistic combination of the advantages of the two imaging modalities.

Simultaneous synthesis and amine-functionalization of single-phase BaYF5:Yb/Er nanoprobe for dual-modal in vivo upconversion fluorescence and long-lasting X-ray computed tomography imaging

In this work, we developed a novel and biocompatible dual-modal nanoprobe based on single-phase amine-functionalized BaYF5:Yb/Er nanoparticles (NPs) for upconversion (UC) fluorescence and in vivo computed X-ray tomography (CT) bioimaging for the first time. High-quality water-soluble amine-functionalized BaYF5:Yb/Er NPs with an average size of 24 nm were synthesized by a facile environmentally friendly hydrothermal method for simultaneous synthesis and surface functionalization. Structure investigation based on the Rietveld refinement method revealed that the as-synthesized BaYF5:Yb/Er NPs present a cubic phase structure, which differs from the previously reported tetragonal structure. Under 980 nm excitation, high-contrast green and red UC emissions were observed from HeLa cells incubated with these amine-functionalized NPs. The UC spectra measured from the NPs incubated with HeLa cells presented only green and red UC emissions without any autofluorescence, further revealing that these NPs are ideal candidates for fluorescent bioimaging. In addition, the cell cytotoxicity test showed low cell toxicity of these NPs. These amine-functionalized NPs were also successfully used as CT agents for in vivo CT imaging because of the efficient X-ray absorption efficiency of Ba and doped Yb ions. A prolonged (2 h) signal enhancement of the spleen in a mouse was observed in CT imaging, which can improve the detection of splenic diseases. More importantly, the simultaneous X-ray and UC in vivo bioimaging was demonstrated in a nude mouse for the first time, indicating the as-prepared UCNPs can be successfully used as dual-modal bioprobes. These results demonstrate that BaYF5:Yb/Er NPs are ideal nanoprobes for dual-modal fluorescent/CT bioimaging with low cytotoxicity, non-autofluorescence, and enhanced detection of the spleen.

PEGylated NaLuF4: Yb/Er upconversion nanophosphors for in vivo synergistic fluorescence/X-ray bioimaging and long-lasting, real-time tracking

Simultaneous in vivo luminescence and X-ray bioimaging in a tissue or animal integrates the advantages of each single-modal imaging technology, and will find widespread application in biological and clinical fields. However, synergistic dual-modal bioimaging that utilizes a new generation of upconversion nanoprobes is still limited. In addition, investigations concentrated on in vivo biodistribution of these nanoprobes may contribute to diagnosis and treatment, but long-term in vivo tracking based on these nanoprobes is rarely reported. In this work, water-soluble NaLuF4: Yb/Er nanophosphors were prepared through modified one-pot simultaneous synthesis and surface modification method. Owing to the outstanding upconverting emissions and large X-ray absorption coefficient/K-edge value of Lu and doped Yb ions, the obtained nanoprobes were successfully used as luminescent nanoprobes and X-ray contrast agents for in vivo synergistic upconversion luminescence and X-ray bioimaging. The in vivo biodistribution of these nanoprobes were observed, and the results based on long-term tracking reveal that the as-prepared nanoprobes first aggregated in the lung of the mouse, transferred to the liver, and finally moved to the spleen.

Multi-functional NaErF4:Yb nanorods: enhanced red upconversion emission, in vitro cell, in vivo X-ray, and T2-weighted magnetic resonance imaging

In this paper, multi-functional hexagonal phase NaErF4:Yb nanorods were synthesized by a facile hydrothermal method. The upconversion luminescence (UCL) intensity and red to green ratio of the multi-functional NaErF4 nanorods can be improved by Yb(3+) doping. More importantly, owing to the decreased distance of Er and Yb, the significant enhancement of red UCL can be obtained, which is different to the usual green UCL of Yb/Er doped NaYF4 host. In addition, the intensity of UCL is strongest when the Yb(3+)-doped concentration reached 30%. The in vitro cell imaging and localized UCL spectra taken from HeLa cells revealed that these NaErF4: 30% Yb(3+) nanorods are ideal nanoprobes with absence of autofluorescence for optical bioimaging. Moreover, these nanorods possess large X-ray absorption ions (Er(3+) and doped Yb(3+)), and were successfully used as contrast agents for in vivo X-ray bioimaging for the first time. In addition to the excellent UCL and X-ray absorption properties, these nanorods present significant paramagnetic properties and can be used as T2-weighted magnetic resonance imaging (MRI) agents. Therefore, these enhanced red UCL NaErF4 nanocrystals with excellent paramagnetic properties and X-ray absorption properties can be used as promising multi-modal nanoprobes for optical bioimaging, MRI, computed X-ray tomography (CT), and may have potential applications in bioseparation.

High quality multi-functional NaErF4 nanocrystals: structure-controlled synthesis, phase-induced multi-color emissions and tunable magnetic properties

In this paper, optical/magnetic multi-functional NaErF4 nanocrystals with high quality, different phases and shapes were synthesized by a simple hydrothermal method using oleic acid as the capping agent. The structure, upconversion luminescence and magnetic properties were characterized by various techniques. The transmission electron microscopy results reveal that the nanocrystals are of high quality and can be self-assembled into a two-dimensional ordered structure. Moreover, the crystal phase and shape can be readily controlled by adjusting the reaction temperature and F− content. The results reveal that high temperature can favor the formation of a hexagonal phase structure and promote the phase transformation from the cubic to hexagonal phase. The phase transformation mechanism based on the free energy theory was discussed in detail. In addition, the F− content plays a critical role in determining the morphology of the final products. A high F− content is beneficial for the formation of the one-dimensional rod-like shape. Interestingly, phase-induced upconversion luminescence color tuning from red to green was observed. All of the as-prepared NaErF4 nanocrystals possess paramagnetic properties at room temperature and the magnetizations of the nanocrystals with spherical-like cubic, cubic, and rod-like shapes were measured as 1.69 emu g−1, 2.53 emu g−1and 2.29 emu g−1 at 20 kOe, respectively, which are larger than most previously reported Gd-based nanocrystals. In addition, T2-weighted magnetic resonance imaging based on these NaErF4 nanocrystals was demonstrated for the first time. Therefore, these tunable upconversion fluorescent NaErF4 nanocrystals with excellent paramagnetic properties can be used as promising dual-modal nanoprobes for optical bioimaging and magnetic resonance imaging, and may have potential applications in bioseparation.

Urchin-like Ce/Tb co-doped GdPO4 hollow spheres for in vivo luminescence/X-ray bioimaging and drug delivery

In this paper, we report a self-sacrificing route for fabrication of the Ce/Tb co-doped GdPO4 hollow spheres under hydrothermal conditions using the Gd(OH)CO3:Ce/Tb precursor as a template and NH4H2PO4 as a phosphorus source. The X-ray diffraction (XRD) patterns show the amorphous crystal nature of the precursor and pure hexagonal phase of the hollow spheres. The microstructures of the as-prepared precursor and hollow spheres were characterized by transmission electron microscopy (TEM) and scanning TEM (STEM) assays. The results reveal the urchin-like morphology of the solid precursor and hollow spheres. Bright green emissions of the spheres have been detected using an ultraviolet (UV) lamp at 288 nm and the calculated CIE coordinates are (0.289, 0.491). The energy transfer mechanism of Ce and Tb ions in the GdPO4 host has been investigated. The quantum efficiency of the hollow spheres was measured to be 61% and the lifetime calculated as 6.94 ms. In addition, the magnetic mass susceptibilities and magnetization of the spheres are found to be 6.39 × 10-5 emu gOe-1 and 1.27 emu g-1 at 20 kOe, respectively. Owing to their excellent downshift luminescence properties, the as-prepared GdPO4:Ce/Tb hollow spheres have been successfully applied in in vivo luminescence and X-ray bioimaging for the first time. Moreover, three-dimensional (3D) in vivo X-ray bioimaging of the mouse can provide the accurate location from multiple directions. The high contrast ratio makes the spheres a promising X-ray contrast agent. Due to the hollow structure, these GdPO4:Ce/Tb hollow spheres were also used as drug delivery systems for doxorubicin (DOX) loading and release. The drug loading efficiency was measured to be 17% at a pH value of 7.4, and the pH-dependent drug release was studied. 47% of the loaded DOX was released within 10 h when pH = 5, while there was only 30% during the same time at pH = 7.4 and it took nearly 48 h to reach a comparable level. The different release nature gives these spheres a promising application in targeted therapy of tumors.