Yuanzhi Shao

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.

Sub-10 nm Monoclinic Gd2O3:Eu3+ Nanoparticles as Dual-Modal Nanoprobes for Magnetic Resonance and Fluorescence Imaging

Monoclinic Gd2O3:Eu(3+) nanoparticles (NPs) possess favorable magnetic and optical properties for biomedical application. However, how to obtain small enough NPs still remains a challenge. Here we combined the standard solid-state reaction with the laser ablation in liquids (LAL) technique to fabricate sub-10 nm monoclinic Gd2O3:Eu(3+) NPs and explained their formation mechanism. The obtained Gd2O3:Eu(3+) NPs exhibit bright red fluorescence emission and can be successfully used as fluorescence probe for cells imaging. In vitro and in vivo magnetic resonance imaging (MRI) studies show that the product can also serve as MRI good contrast agent. Then, we systematically investigated the nanotoxicity including cell viability, apoptosis in vitro, as well as the immunotoxicity and pharmacokinetics assays in vivo. This investigation provides a platform for the fabrication of ultrafine monoclinic Gd2O3:Eu(3+) NPs and evaluation of their efficiency and safety in preclinical application.

Gadolinium3+-doped mesoporous silica nanoparticles as a potential magnetic resonance tracer for monitoring the migration of stem cells in vivo

We investigated the tracking potential of a magnetic resonance imaging (MRI) probe made of gadolinium-doped mesoporous silica MCM-41 (Gd2O3@MCM-41) nanoparticles for transplanted bone mesenchymal stem cells (MSCs) and neural stem cells (NSCs) in vivo. The nanoparticles, synthesized using a one-step synthetic method, possess hexagonal mesoporous structures with appropriate assembly of nanoscale Gd2O3 clusters. They show little cytotoxicity against proliferation and have a lower effect on the inherent differentiation potential of these labeled stem cells. The tracking of labeled NSCs in murine brains was dynamically determined with a clinical 3T MRI system for at least 14 days. The migration of labeled NSCs identified by MRI corresponded to the results of immunofluorescence imaging. Our study confirms that Gd2O3@MCM-41 particles can serve as an ideal vector for long-term MRI tracking of MSCs and NSCs in vivo.

Nanoamplifiers synthesized from gadolinium and gold nanocomposites for magnetic resonance imaging

We have synthesized an efficient and highly sensitive nanoamplifier composed of gadolinium-doped silica nanoparticles and gold nanoparticles (AuNPs). Magnetic resonance imaging (MRI) in vitro and in vivo assays revealed enhancement of signal sensitivity, which may be explained by electron transfer between water and gadolinium-doped nanoparticles, apparent in the presence of gold. In vitro and in vivo evaluation demonstrated nanoamplifier incurred minimal cytotoxicity and immunotoxicity, increased stability, and gradual excretion patterns. Tumor targeted properties were preliminarily determined when the nanoamplifier was injected into mouse models of colon cancer liver metastasis. Furthermore, although AuNPs departed from the nanoamplifiers in specific mice tissues, optical and magnetic resonance imaging was efficient, especially in metastatic tumors. These assays validate our nanoamplifier as an effective MRI signal enhancer with sensitive cancer diagnosis potential.

A Computer-Aided Diagnosis System for Dynamic Contrast-Enhanced MR Images Based on Level Set Segmentation and ReliefF Feature Selection

This study established a fully automated computer-aided diagnosis (CAD) system for the classification of malignant and benign masses via breast magnetic resonance imaging (BMRI). A breast segmentation method consisting of a preprocessing step to identify the air-breast interfacing boundary and curve fitting for chest wall line (CWL) segmentation was included in the proposed CAD system. The Chan-Vese (CV) model level set (LS) segmentation method was adopted to segment breast mass and demonstrated sufficiently good segmentation performance. The support vector machine (SVM) classifier with ReliefF feature selection was used to merge the extracted morphological and texture features into a classification score. The accuracy, sensitivity, and specificity measurements for the leave-half-case-out resampling method were 92.3%, 98.2%, and 76.2%, respectively. For the leave-one-case-out resampling method, the measurements were 90.0%, 98.7%, and 73.8%, respectively.

Magnetic and fluorescent Gd2O3: Yb3+/Ln3+ nanoparticles for simultaneous upconversion luminescence/MR dual modal imaging and nir-induced photodynamic therapy

The development of upconversion nanoparticles (UCNs) for theranostics application is a new strategy toward the accurate diagnosis and efficient treatment of cancer. Here, magnetic and fluorescent lanthanide-doped gadolinium oxide (Gd2O3) UCNs with bright upconversion luminescence (UCL) and high longitudinal relaxivity (r1) are used for simultaneous magnetic resonance imaging (MRI)/UCL dual-modal imaging and photodynamic therapy (PDT). In vitro and in vivo MRI studies show that these products can serve as good MRI contrast agents. The bright upconversion luminescence of the products allows their use as fluorescence nanoprobes for live cells imaging. We also utilized the luminescence-emission capability of the UCNs for the activation of a photosensitizer to achieve significant PDT results. To the best of our knowledge, this study is the first use of lanthanide-doped Gd2O3 UCNs in a theranostics application. This investigation provides a useful platform for the development of Gd2O3-based UCNs for clinical diagnosis, treatment, and imaging-guided therapy of cancer.

NaGd(MoO4)2 nanocrystals with diverse morphologies: controlled synthesis, growth mechanism, photoluminescence and thermometric properties.

Pure tetragonal phase, uniform and well-crystallized sodium gadolinium molybdate (NaGd(MoO4)2) nanocrystals with diverse morphologies, e.g. nanocylinders, nanocubes and square nanoplates have been selectively synthesized via oleic acid-mediated hydrothermal method. The phase, structure, morphology and composition of the as-synthesized products are studied. Contents of both sodium molybdate and oleic acid of the precursor solutions are found to affect the morphologies of the products significantly, and oleic acid plays a key role in the morphology-controlled synthesis of NaGd(MoO4)2 nanocrystals with diverse morphologies. Growth mechanism of NaGd(MoO4)2 nanocrystals is proposed based on time-dependent morphology evolution and X-ray diffraction analysis. Morphology-dependent down-shifting photoluminescence properties of NaGd(MoO4)2: Eu3+ nanocrystals, and upconversion photoluminescence properties of NaGd(MoO4)2: Yb3+/Er3+ and Yb3+/Tm3+ nanoplates are investigated in detail. Charge transfer band in the down-shifting excitation spectra shows a slight blue-shift, and the luminescence intensities and lifetimes of Eu3+ are decreased gradually with the morphology of the nanocrystals varying from nanocubes to thin square nanoplates. Upconversion energy transfer mechanisms of NaGd(MoO4)2: Yb3+/Er3+, Yb3+/Tm3+ nanoplates are proposed based on the energy level scheme and power dependence of upconversion emissions. Thermometric properties of NaGd(MoO4)2: Yb3+/Er3+ nanoplates are investigated, and the maximum sensitivity is determined to be 0.01333 K−1 at 285 K.

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.