Liqin Xiong

Dual-modality in vivo imaging using rare-earth nanocrystals with near-infrared to near-infrared (NIR-to-NIR) upconversion luminescence and magnetic resonance properties

Upconversion luminescence (UCL) imaging is expected to play a significant role in future photoluminescence imaging since it shows advantages of sharp emission lines, long lifetimes, superior photostability and no blinking. To further improve penetration depth, herein, near-infrared to near-infrared (NIR-to-NIR) UCL and magnetic properties were combined into a nanoparticle, and NIR-to-NIR UCL and MRI dual-modal bioimaging in vivo of whole-body animal were developed. Hydrophilic and carboxylic acid-functionalized Tm(3+)/Er(3+)/Yb(3+) co-doped NaGdF(4) upconversion nanophosphors (AA-NPs) were synthesized and showed both NIR-to-visible and NIR-to-NIR luminescence under excitation of 980 nm. Collecting the signal of the upconversion emission from AA-NPs in the visible and NIR range, all UCL imaging of cells, tissues and whole-body animals with different penetration depth showed high contrast. Moreover, AA-NPs showed a high relaxivity of 5.60 s(-1) (mM)(-1) and were successfully applied as contrast agents for magnetic resonance imaging (MRI) in vivo. By means of the combination of UCL imaging and MRI, the distribution of AA-NPs in living animals was studied, and the results indicated that these particles mainly accumulate in the liver and spleen without undesirable stay in the lungs. Therefore, the concept of UCL and MR dual-modality imaging in vivo of whole-body animals using Tm(3+)/Er(3+)/Yb(3+) co-doped NaGdF(4) with NIR-to-NIR upconversion luminescent and magnetic resonance properties can serve as a platform technology for the next-generation of probes for bioimaging in vivo.

Long-term in vivo biodistribution imaging and toxicity of polyacrylic acid-coated upconversion nanophosphors.

Rare-earth upconversion nanophosphors (UCNPs) have become one of the most promising classes of luminescent materials for bioimaging. However, there remain numerous unresolved issues with respect to the understanding of how these nanophosphors interact with biological systems and the environment. Herein, we report polyacrylic acid (PAA)-coated near-infrared to near-infrared (NIR-to-NIR) upconversion nanophosphors NaYF(4):Yb,Tm (PAA-UCNPs) as luminescence probes for long-term in vivo distribution and toxicity studies. Biodistribution results determined that PAA-UCNPs uptake and retention took place primarily in the liver and the spleen and that most of the PAA-UCNPs were excreted from the body of mice in a very slow manner. Body weight data of the mice indicated that mice intravenously injected with 15 mg/kg of PAA-UCNPs survived for 115 days without any apparent adverse effects to their health. In addition, histological, hematological and biochemical analysis were used to further quantify the potential toxicity of PAA-UCNPs, and results indicated that there was no overt toxicity of PAA-UCNPs in mice at long exposure times (up to 115 days). The study suggests that PAA-UNCPs can potentially be used for long-term targeted imaging and therapy studies in vivo.

High Contrast Upconversion Luminescence Targeted Imaging in Vivo Using Peptide-Labeled Nanophosphors

Fluorescence targeted imaging in vivo has proven useful in tumor recognition and drug delivery. In the process of in vivo imaging, however, a high autofluorescence background could mask the signals from the fluorescent probes. Herein, a high contrast upconversion luminescence (UCL) imaging protocol was developed for targeted imaging of tumors based on RGD-labeled upconversion nanophosphors (UCNPs) as luminescent labels. Confocal Z-scan imaging of tissue slices revealed that UCL imaging showed no autofluorescence signal even at high penetration depth (approximately 600 microm). More importantly, region of interest (ROI) analysis of the UCL signal in vivo showed that UCL imaging achieved a high signal-to-noise ratio (approximately 24) between the tumor and the background. These results demonstrate that the UCL imaging technique appears particularly suited for applications in tracking and labeling components of complex biological systems.

Synthesis, characterization, and in vivo targeted imaging of amine-functionalized rare-earth up-converting nanophosphors

Rare-earth up-converting nanophosphors (UCNPs) have great potential to become a new generation of biological luminescent labels, but their use has been limited by difficulties in obtaining water-soluble UCNPs bearing appropriate functional groups. To address this problem, we report herein a simple and efficient procedure for the preparation of amine-functionalized UCNPs by a modified hydrothermal microemulsion route assisted with 6-aminohexanoic acid. The amine content of the resultant UCNPs has been determined to be (9.5+/-0.8) x 10(-5) mol/g, which not only confers excellent dispersibility in aqueous solution, but also allows further conjugation with targeted molecules such as folic acid (FA) as a ligand. By means of the laser scanning up-conversion luminescence microscopy (LSUCLM) and the in vivo up-conversion luminescence (UCL) imaging under excitation at the CW infrared laser at 980 nm, FA-coupled UCNPs have been demonstrated to be effective in targeting folate-receptor overexpressing HeLa cells in vitro and HeLa tumor in vivo and ex vivo. These results indicated that our UCNPs could be used as whole-body targeted UCL imaging agents.

Multimodal‐Luminescence Core–Shell Nanocomposites for Targeted Imaging of Tumor Cells

Uniform silica-coated NaYF(4): 20 mol % Yb, 2 mol % Er nanocomposites with good dispersibility, containing organic dye incorporated in the silica shell and folic acid conjugated on the surface of the shell, were prepared and characterized. The core-shell nanocomposites are 20-22 nm in size, water soluble, and buffer stable, with good photostability and biocompatibility. Folic acid (FA) offers a means of targeting human cells that greatly overexpress the folate receptor (FR). By the use of confocal microscopy and quantitative flow cytometry analysis, we demonstrate the receptor-mediated delivery of FA-conjugated nanocomposites targeting FR-positive cell lines, such as KB cells. The receptor-mediated targeting was confirmed by a comparison with the uptake of these nanocomposites in FR-negative cell lines, such as MCF-7. These results show that the silica-coated upconverting nanophosphor (UCNP) nanocomposites prepared by our strategy can potentially be useful as multimodal bioimaging agents.

Phosphorescence Imaging of Homocysteine and Cysteine in Living Cells Based on a Cationic Iridium(III) Complex

Homocysteine (Hcy) and cysteine (Cys) are crucial to the physiological balance in living systems. Specific detection of intracellular Hcy and Cys is of growing importance. Herein, we demonstrated phosphorescence imaging of intracellular Hcy and Cys using a cationic iridium(III) complex Ir(pba)(2)(bpy)(+).PF(6)(-) [pba = 4-(2-pyridyl)benzaldehyde, bpy = bipyridine] containing aldehyde groups as a luminescent probe. Upon addition of Hcy or Cys to a semiaqueous solution of Ir(pba)(2)(bpy)(+), a change in luminescence from yellow to red was visible to the naked eye. The successful chemical reaction of the aldehyde in Ir(pba)(2)(bpy)(+) with Hcy and Cys to form thiazinane and thiazolidine was confirmed by (1)H NMR. Moreover, complexation with Hcy and Cys disturbed the p-pi conjugation between the aldehyde group and the bpy moiety, and led to the excited states switching to [dpi(Ir)-pi(N(wedge)N)*] (3)MLCT and [pi(C(wedge)N)-pi(N(wedge)N)*] (3)LLCT from (pi-pi*)(pba(-)) (3)IL. Furthermore, the MTT assay was used to determine that the probe has low cytotoxicity. Importantly, cell imaging experiments demonstrated that the probe is membrane permeable and can monitor the changes of Hcy/Cys within living cells in a ratiometric mode.

A highly selective and sensitive fluorescent turn-on sensor for Hg2+ and its application in live cell imaging

A boron-dipyrromethene (BODIPY) derivative containing a tridentate diaza-oxa ligand (8H-BDP) was synthesized as a fluorescent turn-on chemosensor for Hg(2+) with high sensitivity (detection limit < or = 2 ppb), a rapid response time (< or = 5 seconds) and specific selectivity over other cations under physiological conditions and in live cells according to the confocal fluorescence microscopy experiment.

Polymer nanoparticles with an embedded phosphorescent osmium(II) complex for cell imaging

Herein, we report the development of a simple and effective method for embedding a hydrophobic phosphorescent heavy-metal complex into hydrophilic nanoparticles by emulsion polymerization. An osmium(II) complex, [Os(bpy)2(L^L)]2+(PF6−)2, has been synthesized, and its structure has been confirmed by single-crystal X-ray analysis. Phosphorescent polymer nanoparticles (PNPs) with the embedded Os(II) complex have been synthesized by emulsion polymerization. Investigation of its emission properties has shown that PNPs with the embedded Os(II) complex emits red phosphorescence in water, as well as the free Os(II) complex in organic solvents. Moreover, different from the very weak cellular uptake of the Os(II) complex, a good cellular uptake of the PNPs in cytoplasm has been observed, as well as a low cytotoxicity, making them promising candidates for use as living-cell imaging agents.

A photostable fluorescent probe for targeted imaging of tumour cells possessing integrin αvβ3

A one-step S(N)Ar(H) reaction has been used for the synthesis of photostable probe , which has good water solubility and low cytotoxicity; this probe can be used for targeted imaging of tumour cells by virtue of specific binding between integrin alpha(v)beta(3) and an arginine-glycine-aspartic acid tripeptide sequence.