Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imaging.

BACKGROUND: Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. Successful development of safe and effective nanoprobes for in vivo gastric cancer targeting imaging is a big challenge. This study is aimed to develop folic acid (FA)-conjugated silica coated gold nanoclusters (AuNCs) for targeted dual-modal fluorescent and X-ray computed tomography imaging (CT) of in vivo gastric cancer cells. METHOD: AuNCs were prepared, silica was coated on the surface of AuNCs, then folic acid was covalently anchored on the surface of AuNCs, resultant FA-conjugated AuNCs@SiO2 nanoprobes were investigated their cytotoxicity by MTT method, and their targeted ability to FR(+) MGC803 cells and FR(-) GES-1 cells. Nude mice model loaded with MGC803 cells were prepared, prepared nanoprobes were injected into nude mice via tail vein, and then were imaged by fluorescent and X-ray computed tomography (CT) imaging. RESULTS: FA-conjugated AuNCs@SiO2 nanoprobes exhibited good biocompatibility, and could target actively the FR(+) MGC-803 cells and in vivo gastric cancer tissues with 5 mm in diameter in nude mice models, exhibited excellent red emitting fluorescence imaging and CT imaging. CONCLUSION: The high-performance FA-conjugated AuNCs@SiO2 nanoprobes can target in vivo gastric cancer cells, can be used for fluorescent and CT dual-mode imaging, and may own great potential in applications such as targeted dual-mode imaging of in vivo early gastric cancer and other tumors with FR positive expression in near future.

Toxicity assessments of near-infrared upconversion luminescent LaF3:Yb,Er in early development of zebrafish embryos.

This study reports the effects of upconversion nanoparticles (UCNPs) LaF3:Yb,Er on zebrafish, with the aim of investigating UCNPs toxicity. LaF3:Yb,Er were prepared by an oleic acid/ionic liquid two-phase system, and characterized by transmission electron microscope and X-ray powder diffraction. 140 zebrafish embryos were divided into six test groups and one control group, and respectively were injected into 5, 25, 50, 100, 200, 400 µg/mL LaF3:Yb,Er@SiO2 solution, and respectively were raised for 5 days. Each experiment was repeated ten times. Results showed that water-soluble LaF3:Yb,Er were successfully prepared, and did not exhibit obvious toxicity to zebrafish embryos under 100 µg/mL, but exhibited chronic toxicities 200 µg/mL in vivo, resulting in malformations and delayed hatching rate and embryonic and larval development. The excretion channels of LaF3:Yb,Er in adult zebrafish were mainly found in the intestine after being injected evenly for 24 h. In conclusion, the exploration of LaF3:Yb,Er for in vivo applications in animals and humans must consider UCNPs biocompatibility.

Phase and size controllable synthesis of NaYbF4 nanocrystals in oleic acid/ionic liquid two-phase system for targeted fluorescent imaging of gastric cancer.

Upconversion nanocrystals with small size and strong fluorescent signals own great potential in applications such as biomolecule-labeling, in vivo tracking and molecular imaging. Herein we reported that NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with small size and strong fluorescent signals were controllably synthesized by oleic acid (OA)/ ionic liquid (IL) two-phase system for targeted fluorescent imaging of gastric cancer in vivo. The optimal synthesis condition of NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals by OA/IL two-phase system was established, adding more metal ion such as Na(+) ion could facilitate the size control and crystal-phase transition, more importantly, markedly enhancing fluorescent intensity of beta-phase nanocrystals compared with traditional methods. Alpha-phase NaYbF4, 2%Tm upconversion nanocrystals with less than 10nm in diameter and beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with 30 nm or so in diameter and strong fluorescent signals were obtained, these synthesized nanocrystals exhibited very low cytotoxicity. Folic acid-conjugated silica-modified beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals were prepared, could actively target gastric cancer tissues implanted into nude mice in vivo, and realized targeted fluorescent imaging. Folic acid-conjugated silica-modified NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals show great potential in applications such as targeted near infared radiation fluorescent imaging, magnetic resonance imaging and targeted therapy of gastric cancer in the near future.

One-pot hydrothermal synthesis of lanthanide ions doped one-dimensional upconversion submicrocrystals and their potential application in vivo CT imaging.

Multi-functional rare-earth Yb(3+) and Ln(3+) (Ln = Er, Tm and Ho) ions doped one-dimensional (1-D) upconversion submicrocrystals (NaYF(4) and NaGdF(4)) possessing upconversion luminescence, biocompatibility and magnetic properties have been synthesized by a one-pot hydrothermal method. Rare-earth Yb(3+) and Ln(3+) ions doped NaYF(4) microrods (~1 µm in diameter, 3-5 µm in length) exhibit porous properties, and the average pore sizes are ~28.2 nm. They show paramagnetism in the magnetic range of -60 to -2 kOe and 2 to 60 kOe at 300 K, and exhibit near superparamagnetic behaviour at the magnetic range of -2 to 2 kOe. Saturation magnetization was ~12.1 emu g(-1) at 2 K. The Yb(3+) and Ln(3+) ions doped NaGdF(4) submicrocrystals (~100 nm in diameter, 200-300 nm in length) show paramagnetism at 300 K, and exhibit superparamagnetic behaviour with a saturation magnetization of 129.2 emu g(-1) at 2 K. The magnetic properties of Yb(3+) and Ln(3+) ions doped 1-D upconversion submicrocrystals indicate they can be used for drug targeting under a magnetic field. Their unique upconversion emission (green for Yb(3+)/Er(3+) and blue for Yb(3+)/Tm(3+)) under 980 nm laser excitation indicate that they could be used for specific luminescent immunolabeling and imaging. MTT assays reveal that 1-D upconversion submicrocrystals have satisfactory bio-affinity, where the viability keeps in good state even at a concentration of 500 µg mL(-1), which is much higher than the concentration usually used in cell labelling. Luminescent microscopy images show that the morphologies of the cytoskeleton and cell nucleus are well maintained after incubating different concentrations of 1-D upconversion submicrocrystals. After injecting upconversion submicrocrystals into the mice (tumor sites or back normal tissue), a clearly distinguished CT signal was observed, indicating the synthesized 1-D submicrocrystals are effective for CT imaging in vivo.

Folic acid-conjugated LaF3:Yb,Tm@SiO2 nanoprobes for targeting dual-modality imaging of upconversion luminescence and X-ray computed tomography.

Development of multimodal contrast agents for in vivo simultaneous multimodality imaging is an emerging interdiscipline that is paving the avenue toward the goal of personalized medicine. Herein, folic acid-conjugated silica-modified LaF(3):Yb,Tm upconversion nanoparticles (UCNPs@SiO(2)-FA) with high La content in a single particle were strategically designed and prepared for simultaneously targeting dual-modality imaging of upconversion luminescence (UCL) and X-ray computed tomography (CT). LaF(3) UCNPs were synthesized by a novel oleic acid (OA)/ionic liquid (IL) two-phase system. Afterward, a folic acid molecule was covalently anchored on the surface of UCNPs with a silane coupling agent. The UCNPs@SiO(2)-FA exhibits good stability, water dispersibility and solubility, low cytotoxicity, good biocompatibility, highly selective targeting, excellent X-ray attenuation, and UCL emission under excitation at 980 nm. In vivo UCL and CT images of mice show the UCNPs@SiO(2)-FA can be used in targeting dual-modality imaging. These results suggest that the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for targeting dual-modality imaging of UCL and CT.

Phase- and size-controllable synthesis of hexagonal upconversion rare-earth fluoride nanocrystals through an oleic acid/ionic liquid two-phase system.

Herein, we introduce a facile, user- and environmentally friendly (n-octanol-induced) oleic acid (OA)/ionic liquid (IL) two-phase system for the phase- and size-controllable synthesis of water-soluble hexagonal rare earth (RE = La, Gd, and Y) fluoride nanocrystals with uniform morphologies (mainly spheres and elongated particles) and small sizes (<50 nm). The unique role of the IL 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF(6)) and n-octanol in modulating the phase structure and particle size are discussed in detail. More importantly, the mechanism of the (n-octanol-induced) OA/IL two-phase system, the formation of the RE fluoride nanocrystals, and the distinctive size- and morphology-controlling capacity of the system are presented. BmimPF(6) is versatile in term of crystal-phase manipulation, size and shape maintenance, and providing water solubility in a one-step reaction. The luminescent properties of Er(3+)-, Ho(3+)-, and Tm(3+)-doped LaF(3), NaGdF(4), and NaYF(4) nanocrystals were also studied. It is worth noting that the as-prepared products can be directly dispersed in water due to the hydrophilic property of Bmim(+) (cationic part of the IL) as a capping agent. This advantageous feature has made the IL-capped products favorable in facile surface modifications, such as the classic Stober method. Finally, the cytotoxicity evaluation of NaYF(4):Yb,Er nanocrystals before and after silica coating was conducted for further biological applications.

A general strategy for the synthesis of upconversion rare earth fluoride nanocrystals via a novel OA/ionic liquid two-phase system.

Herein we report a general strategy to synthesize highly uniform and monodisperse rare earth fluoride nanocrystals through a novel OA/ionic liquid two-phase system, while water-soluble hexagonal NaREF(4) nanocrystals are obtained by adding n-octanol.