Wenyong Hu

Ligand-free gadolinium oxide for in vivo T1-weighted magnetic resonance imaging

Gadolinium oxide (Gd2O3), which can be used as a T1-weighted magnetic resonance imaging (MRI) contrast agent, has attracted intense attention in recent years. In this paper, ligand-free monoclinic Gd2O3 nanocrystals of 7.1 nm in diameter are synthesized by a simple and green approach, namely microsecond laser ablation of a gadolinium (Gd) target in deionized water. These nanocrystals obtain high r1 relaxivity of 5.53 s(-1) mM(-1), and their low toxicity was demonstrated by the cell viability of S18 cells and apoptosis in RAW264.7 cells. In vitro and in vivo MR images show these particles to be good T1-weighted MRI contrast agents. Base on the experimental results and theoretical analysis, we suggest that the purity of the Gd2O3 contributes to its high r1 relaxivity value, while the low toxicity is due to its good crystallinity. These findings show that laser ablation in liquid (LAL) is a promising strategy to synthesize ligand-free monoclinic Gd2O3 nanocrystals for use as high efficient T1-weighted MRI contrast agents.

The properties of Gd2O3-assembled silica nanocomposite targeted nanoprobes and their application in MRI.

The feasibility of the gadolinium-doped mesoporous silica nanocomposite Gd(2)O(3)@MCM-41 as a safe, effective MRI nanoprobe has been validated in the current investigation systematically from atomistic and molecular modeling to its synthesis and characterization on in vivo MR imaging and biocompatibility. The first-principles calculation indicates that it is nearly impossible for toxic Gd ions to dissociate freely from silica. The biocompatibility studies confirm that the nanocomposite is lack of any potential toxicity; the biodistribution studies reveal a greater accumulation of the nanocomposite in liver, spleen, lung and tumor than in kidney, heart and brain; the excretion studies show that the nanocomposite can be cleared nearly 50% via the hepatobiliary transport mechanism after 1.5 months of injection. A larger water proton relaxivity r(1) and a better T(1)-weighted phantom MR imaging capability were detected in the nanocomposite than in the commercially available gadolinium diethylenetriaminepentaacetate. The results demonstrate that the nanocomposite is superior to the commercial counterpart in terms of contrast enhancement with a satisfactory biocompatibility, and it has a high potential to be developed into a safe and effective targeted probe for in vivo molecular imaging of cancer.

High longitudinal relaxivity of ultra-small gadolinium oxide prepared by microsecond laser ablation in diethylene glycol

Ultra-small gadolinium oxide (Gd2O3) can be used as T1-weighted Magnetic Resonance Imaging (MRI) contrast agent own to its high longitudinal relaxivity (r1) and has attracted intensive attention in these years. In this paper, ultra-small Gd2O3 nanoparticles of 3.8 nm in diameter have been successfully synthesized by a microsecond laser ablating a gadolinium (Gd) target in diethylene glycol (DEG). The growth inhibition effect induced by the large viscosity of DEG makes it possible to synthesize ultra-small Gd2O3 by laser ablation in DEG. The r1 value and T1-weighted MR images are measured by a 3.0 T MRI spectroscope. The results show these nanoparticles with a high r1 value of 9.76 s−1 mM−1 to be good MRI contrast agents. We propose an explanation for the high r1 value of ultra-small Gd2O3 by considering the decreasing factor (surface to volume ratio of the nanoparticles, S/V) and the increasing factor (water hydration number of the Gd3+ on Gd2O3 surface, q), which offer a new look into the relaxivity stud...

High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells.

Nanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers.

Hollow-structured upconverting sesquioxide targeted nanoprobes for magnetic resonance and fluorescence combined imaging

Herein, hollow-structured Gd2O3:RE3+/Yb3+ (RE = Er, Ho, Tm) nanoparticles (NPs) were prepared via a urea-based chemical coprecipitation method followed by subsequent calcination and etching. Under 980 nm near-infrared (NIR) irradiation, upconversion (UC) emission gains the highest intensity of red, green and blue peaks for Gd2O3:Er3+/Yb3+, Gd2O3:Ho3+/Yb3+ and Gd2O3:Tm3+/Yb3+ NPs respectively. The corresponding fluorescence in-cell images exhibit bright visible light. The continuous color-tunable UC emission of each spectrum was investigated by increasing the concentration of the sensitizer Yb3+ ions from 0 to 20 mol% with the most intense red, green and blue emission achieved. The structure, morphology, components and magnetic property of Gd2O3:Ho3+/Yb3+ NPs were investigated intensively. The results show that the NPs possess a distinctly hollow structure and uniform spherical shape, and are well-crystallized and highly monodispersed with a mean diameter of 118 nm. Due to the designed hollow structure which is of benefit to water contact of a large number of Gd3+ on the surface, the measured T1 relaxivity of the NPs is nearly 5 times larger than the relaxivity of the commercial gadolinium diethylenetriaminepentaacetate (Gd-DTPA). The relaxation enhancement in the hollow-structured Gd2O3:RE3+/Yb3+ (RE = Er, Ho, Tm) NPs is addressed in the framework of Solomon–Bloembergen–Morgan theory. The biocompatibility studies in 293 and HeLa cells indicate that the hollow NPs have no observable cytotoxicity at a concentration up to 200 μg ml−1. All these results demonstrate that the hollow-structured nanocomposite has the potential to be developed into a safe and highly efficient magnetic resonance and fluorescence nanoprobe for in-cell molecular imaging of cancer.

Fluorescein isothiocyanate embedded silica spheres in gadolinium carbonate shells as novel magnetic resonance imaging and fluorescence bi-modal contrast agents

In this study, four bi-modal core-shelled contrast agents of SiO2(FITC)@Gd2O(CO3)2·H2O with varying shell thicknesses but the same cores have been prepared via a two-step wet chemistry method. The four samples were quite close to sphericity and their averaged diameters were 127, 140, 148.7 and 174.0 nm. The composition of their shells was also examined. As the shell thickness increased, the fluorescence intensity halved but the longitudinal relaxivity remained high (28, 29, 27, 24 mM−1 s−1). The measured relaxivities of the samples were more than 5.8 times higher than the relaxivity of Gd-DTPA-BMA in a 0.55 T MR (magnetic resonance) system. The levels of cytotoxicity were tested on four cell lines (293, HeLa, HFL1, MCF-7) and the results indicated that the samples were safe. The intracellular fluorescence in HeLa cells was clearly observed using laser confocal microscopy. These results showed that this material had potential for application in MR-fluorescence bi-modal imaging.

Scaling dynamic response and destructive metabolism in an immunosurveillant anti-tumor system modulated by different external periodic interventions

On the basis of two universal power-law scaling laws, i.e. the scaling dynamic hysteresis in physics and the allometric scaling metabolism in biosystem, we studied the dynamic response and the evolution of an immunosurveillant anti-tumor system subjected to a periodic external intervention, which is equivalent to the scheme of a radiotherapy or chemotherapy, within the framework of the growth dynamics of tumor. Under the modulation of either an abrupt or a gradual change external intervention, the population density of tumors exhibits a dynamic hysteresis to the intervention. The area of dynamic hysteresis loop characterizes a sort of dissipative-therapeutic relationship of the dynamic responding of treated tumors with the dose consumption of accumulated external intervention per cycle of therapy. Scaling the area of dynamic hysteresis loops against the intensity of an external intervention, we deduced a characteristic quantity which was defined as the theoretical therapeutic effectiveness of treated tumor and related with the destructive metabolism of tumor under treatment. The calculated dose-effectiveness profiles, namely the dose cumulant per cycle of intervention versus the therapeutic effectiveness, could be well scaled into a universal quadratic formula regardless of either an abrupt or a gradual change intervention involved. We present a new concept, i.e., the therapy-effect matrix and the dose cumulant matrix, to expound the new finding observed in the growth and regression dynamics of a modulated anti-tumor system.