Huixia Wu

Water-soluble superparamagnetic manganese ferrite nanoparticles for magnetic resonance imaging.

We report here a thermal decomposition approach to the synthesis of water-soluble superparamagnetic manganese ferrite (MnFe(2)O(4)) nanoparticles (NPs) for magnetic resonance (MR) imaging applications. In this approach, tetraethylene glycol was utilized as a coordination and stabilization agent, rendering the NPs water-soluble and stable. The formed NPs had a diameter of 7 nm with a narrow size distribution, and were superparamagnetic with a saturated magnetization (Ms) of 39 emu/g. In vitro cytotoxicity test revealed that the MnFe(2)O(4) NPs were biocompatible at a particle concentration below 200 microg/mL. The transverse relaxivity of MnFe(2)O(4) NPs in water and cells after incubation were determined to be 189.3mm(-1)s(-1) and 36.8mm(-1)s(-1) based on iron concentration, respectively. In vivo MR imaging studies in conjunction with inductively coupled plasma-atomic emission spectroscopy showed that the MnFe(2)O(4) NPs were preferentially accumulated in liver after intravenous injection for 4h. This suggests that the developed MnFe(2)O(4) NPs can serve as a sensitive MR imaging contrast agent for liver imaging. By appropriately modifying or functionalizing the surface of the NPs, these particles may be used for MR detection of other diseases.

Solvothermal synthesis of cobalt ferrite nanoparticles loaded on multiwalled carbon nanotubes for magnetic resonance imaging and drug delivery.

Multiwalled carbon nanotube (MWCNT)/cobalt ferrite (CoFe(2)O(4)) magnetic hybrids were synthesized by a solvothermal method. The reaction temperature significantly affected the structure of the resultant MWCNT/CoFe(2)O(4) hybrids, which varied from 6nm CoFe(2)O(4) nanoparticles uniformly coated on the nanotubes at 180°C to agglomerated CoFe(2)O(4) spherical particles threaded by MWCNTs and forming necklace-like nanostructures at 240°C. Based on the superparamagnetic property at room temperature and high hydrophilicity, the MWCNT/CoFe(2)O(4) hybrids prepared at 180°C (MWCNT/CoFe(2)O(4)-180) were further investigated for biomedical applications, which showed a high T(2) relaxivity of 152.8 Fe mM(-1)s(-1) in aqueous solutions, a significant negative contrast enhancement effect on cancer cells and, more importantly, low cytotoxicity and negligible hemolytic activity. The anticancer drug doxorubicin (DOX) can be loaded onto the hybrids and subsequently released in a sustained and pH-responsive way. The DOX-loaded hybrids exhibited notable cytotoxicity to HeLa cancer cells due to the intracellular release of DOX. These results suggest that MWCNT/CoFe(2)O(4)-180 hybrids may be used as both effective magnetic resonance imaging contrast agents and anticancer drug delivery systems for simultaneous cancer diagnosis and chemotherapy.

The behavior after intravenous injection in mice of multiwalled carbon nanotube / Fe3O4 hybrid MRI contrast agents

Fe(3)O(4) nanoparticles were in situ loaded on the surface of multiwalled carbon nanotubes (MWCNTs) by a solvothermal method using diethylene glycol and diethanolamine as solvents and complexing agents. The as-prepared MWCNT/Fe(3)O(4) hybrids exhibited excellent hydrophilicity, superparamagnetic property at room temperature, and a high T(2) relaxivity of 175.5 mM(-1) s(-1) in aqueous solutions. In vitro experiments revealed that MWCNT/Fe(3)O(4) had an excellent magnetic resonance imaging (MRI) enhancement effect on cancer cells, and importantly, they displayed low cytotoxicity and neglectable hemolytic activity. After intravenous administration, the T(2)-weighted MRI signal in the liver and spleen of mice decreased significantly, suggesting the potential application of the hybrids as MRI contrast agents. The organ biodistribution studies, histological analyses and elimination investigations showed that the hybrids were uptaken by the liver, lung and spleen after intravenous injection, and could be excreted from the liver and kidney.

Graphene oxide-BaGdF5 nanocomposites for multi-modal imaging and photothermal therapy

By using a solvothermal method in the presence of polyethylene glycol (PEG), BaGdF5 nanoparticles are firmly attached on the surface of graphene oxide (GO) nanosheets to form the GO/BaGdF5/PEG nanocomposites. The resulting GO/BaGdF5/PEG shows low cytotoxicity, positive magnetic resonance (MR) contrast effect and better X-ray attenuation property than Iohexol, which enables effective dual-modality MR and X-ray computed tomography (CT) imaging of the tumor model in vivo. The enhanced near-infrared absorbance, good photothermal stability and efficient tumor passive targeting of GO/BaGdF5/PEG result in the highly efficient photothermal ablation of tumor in vivo after intravenous injection of GO/BaGdF5/PEG and the following 808-nm laser irradiation (0.5 W/cm(2)). The histological and biochemical analysis data reveal no perceptible toxicity of GO/BaGdF5/PEG in mice after treatment. These results indicate potential application of GO/BaGdF5/PEG in dual-modality MR/CT imaging and photothermal therapy of cancers.

Biocompatiable hollow silica microspheres as novel ultrasound contrast agents for in vivo imaging

Surface PEGylated hollow silica microspheres (PEG–HSS) of ∼1250 nm in diameter were prepared by coating a thin layer of amino functionalized silica on the template of positive charged polystyrene, removing the template in THF solution, and further coupling the HSS with methoxy polyethylene glycol propionic acid (mPEG–COOH). Cytotoxicity tests, hemolysis assays, and confocal fluorescent imaging proved that the PEG–HSS have low cytotoxicity, good blood compatibility and cell permeability. Further in vitro ultrasound imaging of the as-prepared PEG–HSS in both physiological saline solution and human blood was investigated under different imaging conditions, including different ultrasound frequencies, mechanical indexes (MIs), and different PEG–HSS concentrations, which demonstrated obvious signal enhancement. In vivo ultrasound imaging was conducted on male rats after intra-testicle injection of the PEG–HSS. These results indicate that the PEG–HSS have great potential in application as a novel ultrasound contrast agent.

Perfluoropentane-Encapsulated Hollow Mesoporous Prussian Blue Nanocubes for Activated Ultrasound Imaging and Photothermal Therapy of Cancer

Hollow mesoporous nanomaterials have gained tremendous attention in the fields of nanomedicine and nanobiotechnology. Herein, n-perfluoropentane (PFP)-encapsulated hollow mesoporous Prussian blue (HPB) nanocubes (HPB-PFP) with excellent colloidal stability have been synthesized for concurrent in vivo tumor diagnosis and regression. The HPB shell shows excellent photothermal conversion efficiency that can absorb near-infrared (NIR) laser light and convert it into heat. The generated heat can not only cause tumor ablation by raising the temperature of tumor tissue but also promote the continuous gasification and bubbling of encapsulated liquid PFP with low boiling point. These formed PFP bubbles can cause tissue impedance mismatch, thus apparently enhancing the signal of B-mode ultrasound imaging in vitro and generating an apparent echogenicity signal for tumor tissues of nude mice in vivo. Without showing observable in vitro and in vivo cytotoxicity, the designed biocompatible HPB-PFP nanotheranostics with high colloidal stability and photothermal efficiency are anticipated to find various biomedical applications in activated ultrasound imaging-guided tumor detection and therapy.

Facile synthesis of amino-functionalized hollow silica microspheres and their potential application for ultrasound imaging

By using the positive charged polystyrene (PS) microsphere as template, mono-disperse amino-(-NH(2)) functionalized hollow silica microspheres (HSMS-NH(2)) with ~1310 nm in diameter and uniform shells were successfully prepared with a modified sol-gel process. The amino functionalized silica were coated on the PS microspheres via ammonia catalysis, co-hydrolysis and condensation of TEOS and APTES, and then the PS templates were selectively dissolved in THF solution to form the functional hollow microspheres. The controllable thickness (35-85 nm) and amino density (2.46×10(-5)-6.18×10(-5) mol/g) of the shells could be facilely tuned by changing the amount of TEOS and APTES. In vitro ultrasound images of as-prepared HSMS-NH(2) with different concentrations in the physiological saline solution were further investigated. The obvious signal enhancement indicates that as-prepared HSMS-NH(2) has a great potential application for ultrasound imaging.

Surfactant-controlled morphology and magnetic property of manganese ferrite nanocrystal contrast agent

MnFe(2)O(4) nanocrystals (NCs) coated with three different surfactants (oleic acid, oleylamine or 1,2-hexadecanediol) and their mixtures, with sizes in range 6-12 nm, were synthesized by high-temperature decomposition of organometallic precursors. The effects of morphology and surface chemistry of MnFe(2)O(4) NCs on the magnetic properties were systematically investigated by comparing their saturation magnetization values and their capability to improve the negative contrast for magnetic resonance imaging (MRI) after converting the hydrophobic NCs to hydrophilic ones by a ligand exchange protocol. An important finding is that the magnetization values and proton relaxivity rates of MnFe(2)O(4) NCs are strongly dependent on the size and surface state of the particles that covalently bonded with different hydrophobic ligands before ligand exchange. In particular, monodisperse cubic MnFe(2)O(4) NCs could be obtained when oleylamine and 1,2-hexadecanediol were used as mixed stabilizers, and showed excellent morphology and magnetic properties. Furthermore, the low cytotoxicity and good cell uptake MR imaging of the dopamine capped MnFe(2)O(4) NCs make them promising candidates for use as bio-imaging probes.

Metal sulfide coated multiwalled carbon nanotubes synthesized by an in situ method and their optical limiting properties

A metal sulfide such as ZnS, CdS, Ag(2)S or PbS was coated on the sidewall of multiwalled carbon nanotubes (MWCNTs) by an in situ wet chemical synthesis approach via noncovalent functionalization of MWCNTs with a polyelectrolyte (polyethylenimine or poly(diallyldimethylammonium chloride)) without causing significant electronic and structural modification of the carbon nanotubes. Extensive characterizations of the fabricated nanocomposites have been performed using x-ray diffraction, transmission electron microscopy (TEM), high resolution TEM, energy dispersive x-ray spectroscopy, selected area electron diffraction, thermal gravimetric analysis, Fourier transform IR spectra, UV-vis spectra and x-ray photoelectron spectroscopy. The coating layers were composed of metal sulfide nanoparticles with a mean size of less than 10 nm. The optical limiting property measurements for some metal sulfide coated MWCNTs were carried out by the open-aperture z-scan technique. The results demonstrate that the samples suspended in water showed optical limiting behavior better than that of purified MWCNTs.

Hydrophilic graphene oxide/bismuth selenide nanocomposites for CT imaging, photoacoustic imaging, and photothermal therapy

A nanotheranostic agent has been fabricated by direct deposition of Bi2Se3 nanoparticles on graphene oxide (GO) in the presence of polyvinylpyrrolidone (PVP) using a one-pot solvothermal method. The resulting GO/Bi2Se3/PVP nanocomposites show low in vitro cytotoxicity, negligible hemolytic activity and little in vivo toxicity. GO/Bi2Se3/PVP nanocomposites could serve as an efficient bimodal contrast agent to simultaneously enhance X-ray computed tomography imaging and photoacoustic imaging in vivo. In addition, the nanocomposites exhibit significant photothermal cytotoxicity to cancer cells under 808 nm laser irradiation. After intratumoral or intravenous injection of the nanocomposites, irreversible photothermal ablation of tumors in the mouse model is successfully achieved by using 808 nm laser irradiation. All of the positive results highlight that the GO/Bi2Se3/PVP nanocomposites can be developed as a promising nanoplatform for efficient tumor theranostic applications.