Jing Huang

Emory University, Atlanta, Georgia, United States

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Publications (32)116.05 Total impact

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    ABSTRACT: We report a novel drug delivery system composed of layer-by-layer (LBL) milk protein casein (CN) coated iron oxide nanoparticles. Doxorubicin (DOX) and indocyanine green (ICG) were selected as model drug molecules, which were incorporated into the inner polymeric layer, and subsequently coated with casein. The resulting casein coated iron oxide nanoparticles (CN-DOX/ICG-IO) were stable in the acidic gastric condition with the presence of gastric protease. On the other hand, the loaded drugs were released when the casein outer layer was gradually degraded by the intestinal protease in the simulated intestine condition. Such unique properties enable maintenance of the bioactivity of the drugs and thus enhance the drug delivery efficiency. Ex vivo experiments showed that the LBL CN-DOX-IO improved the translocation of DOX across microvilli and its absorption in the small intestine sacs. In vivo imaging of mice that were orally administered with these LBL CN-ICG-IO nanostructures further confirmed that the reported drug delivery vehicles could pass the stomach without significant degradation, and then accumulated in the small intestine. In addition, the magnetic iron oxide nanoparticle core offered an MRI contrast enhancing capability for in vivo imaging guided drug delivery. Therefore, the reported LBL CN-DOX/ICG-IO is a promising oral drug delivery nanoplatform, especially for drugs that are poorly soluble in water or degradable in the gastric environment.
    Biomaterials 11/2014; · 8.31 Impact Factor
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    ABSTRACT: Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAM-IONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.
    Proceedings of the National Academy of Sciences of the United States of America. 09/2014;
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    ABSTRACT: CCDC134 is a poorly characterized secreted protein that may act as an immune cytokine. Here we show that CCDC134 is differentially expressed on resting and activated immune cells and that it promotes CD8+ T cell activation, proliferation and cytotoxicity by augmenting expression of the T cell effector molecules IFN-γ, TNF-α, granzyme B and perforin. CCDC134 facilitated infiltration of CD8+ T cells with enhanced cytolytic activity into tumors, demonstrating strong antitumor effects in a CD8+ T cell-dependent manner. Mechanistically, in CD8+ T cells exposure to CCDC134 promoted cell proliferation through the JAK3-STAT5 pathway, a classic feature of many cytokines of the common γ-chain (γc) cytokine receptor family. Overall, our results provide evidence that CCDC134 may serve as a member of the γc cytokine family, and they show illustrate its potent antitumor effects by augmenting CD8+ T cell-mediated immunity.
    Cancer research. 08/2014;
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    ABSTRACT: Ultrafine sub-5 nm magnetic iron oxide nanoparticles coated with oligosaccharides (SIO) with dual T1–T2 weighted contrast enhancing effects and fast clearance have been developed as magnetic resonance imaging (MRI) contrast agents. Excellent water solubility, biocompatibility and high stability of such sub-5 nm SIO nanoparticles were achieved by using the “in situ polymerization” coating method, which enables glucose to form oligosaccharides directly on the surface of hydrophobic iron oxide nanocrystals. Reported ultrafine SIO nanoparticles exhibit a longitudinal relaxivity (r1) of 4.1 mM−1 s−1 and a r1/r2 ratio of 0.25 at 3 T (clinical field strength), rendering improved T1 or “brighter” contrast enhancement in T1-weighted MRI in addition to typical T2 or “darkening” contrast of conventional iron oxide nanoparticles. Such dual contrast effects can be demonstrated by liver imaging with T2 “darkening” contrast in the liver parenchyma but T1 “bright” contrast in the hepatic vasculature. More importantly, this new class of ultrafine sub-5 nm iron oxide nanoparticles showed much faster body clearance than those with larger sizes, promising better safety for clinical applications.
    J. Mater. Chem. B. 07/2014;
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    ABSTRACT: Non-B cell immunoglobulins (Igs) are widely expressed in epithelial cancer cells. The past 20 years of research have demonstrated that non-B cell Igs are associated with cancer cell proliferation, the cellular cytoskeleton and cancer stem cells. In this study we explored the transcriptional mechanism of IgM production in non-B cells. The promoter region of a V-segment of the heavy mu chain gene (VH6-1) was cloned from a colon cancer cell line HT-29. Next, the promoter activities in non-B cells and B-cells were detected using the dual-luciferase reporter assay. Then the transcription factor binding to the promoter regions was evaluated by electrophoretic mobility shift assays (EMSAs) and gel supershift experiments. Our data showed that the sequence 1200 bp upstream of VH6-1 exhibited promoter activity in both B and non-B cells. No new regulatory elements were identified within the region 1200 bp to 300 bp upstream of VH6-1. In addition, Oct-1 was found to bind to the octamer element of the Ig gene promoter in cancer cells, in contrast to B cells, which utilize the transcriptional factor Oct-2. The regulatory mechanisms among different cell types controlling the production of IgM heavy chains are worth discussing.
    Cancer Cell International 01/2014; 14(1):114. · 2.09 Impact Factor
  • Hui Mao, Jing Huang, Liya Wang
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    ABSTRACT: PURPOSE A new class of high r1 relaxivity, sub-5 nm, super small iron oxide nanoparticles with oligosaccharide coating as T1-weighted MRI contrast agents while providing reverse T2 contrast was used in MRI angiography. METHOD AND MATERIALS The sSIO nanoparticles were obtained from the encapsulation of iron oxide core in a thin oligosaccharide shell through in situ polymerization. SIO solutions with different concentrations were examined by a 3T MRI scanner using T1- and T2-weighted fast spin echo sequences, inversion recovery turbo spin echo sequence and multi-echo T2-weighted spin echo sequence. R1 and R2 relaxivities were calculated by fitting signal changes in multi-IR T1 and multi-TE T2 images using simple exponential equations. SIO with different sizes and Gd-BOPTA were intravenously administrated into mice. Fat suppressed T1-weighted spin echo images were obtained to investigate the contrast changes in liver, kidney and iliac artery at the different time points. RESULTS The prepared sSIO has an r1 value of 4.2 mM-1s-1 and a high r1/r2 ratio (0.28), which is competitive with commercial Gd-based contrast agent. Significant T1 contrast enhancement in the kidney and iliac artery were evidenced in in vivo MRI after intravenously administration of sSIO in mice, similar to that observed in Gd-BOPTA enhanced MRI. The positive contrast enhancement is attributed to the small size and the reduced susceptibility of the nanoparticles, as well as the excellent colloidal stability in physiological environment. Such T1 contrast enhancement is not obvious when using a larger size SIO-10 or 20. Interestingly, uptake of SIO-3 in liver led to strong T2 effect or signal drop in liver further improves the image quality for visualizing liver tissue and hepatic vasculature in T1 weighted MRI. Futhermore, SIO-3 has a much longer blood retention time than small molecule Gd for prolonged imaging time for organs of interest, providing a potential long half time T1 weighted imaging agents for imaging of vasculture of disease tissues. CONCLUSION sSIO-3 has a much longer blood retention time than small molecule Gd for prolonged imaging time for organs of interest, providing a potential long half time T1 weighted MR imaging agents for MRI Angiography. CLINICAL RELEVANCE/APPLICATION The suprasmall SIOs exhibit excellent T1 contrast in vivo MRI studies, especially for kidney and iliac artery, providing a potential long half time blood pool MR imaging agents.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: PurposeThe purpose of this study was to investigate an ultrashort echo time (UTE) imaging approach for improving the detection of receptor targeted magnetic nanoparticles in cancer xenograft models using positive contrast. Materials and Methods Iron oxide nanoparticle (IONP) conjugated with tumor targeting ligands were prepared. A 3D UTE gradient echo sequence with the shortest TE of 0.07 msec was evaluated on a 3T magnetic resonance imaging (MRI) scanner using IONP solution, cancer cells bound with targeted IONPs and orthotopic human pancreatic, and breast cancer mouse models administered tumor targeting IONPs. A simulation was performed to analyze contrast-to-noise ratios (CNR) of UTE images and subtraction of the images obtained UTE and longer TE (SubUTE). T2-weighted imaging and T2 relaxometry mapping were applied for comparison and validation. ResultsUTE and SubUTE images showed positive contrast in pancreatic tumors accumulated with EGFR targeted ScFvEGFR-IONPs and mammary tumors accumulated with uPAR targeted ATF-IONPs. The positive contrast observed in UTE images was consistent with the negative contrast observed in the T2-weighted images. A flip angle of 10° and a maximal possible TE for the second echo are suitable for SubUTE imaging. ConclusionUTE imaging is capable of detecting tumor targeted IONPs in vivo with positive contrast in molecular MRI applications. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 11/2013; · 2.57 Impact Factor
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    ABSTRACT: Immunoglobulin (Ig), a characteristic marker of B cells, has been reported to be expressed in epithelial cells, with a suggested role in their growth and survival. We have previously reported that IgG heavy chain is expressed in acute myeloid leukemia (AML), but not in the monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. In the present study, we assessed IgM heavy chain expression and repertoire in human myeloid cells. We detected VHμDJHμ rearrangement and expression in 7/7 AML cell lines, 7/14 primary myeloblasts from AML patients, and interestingly, 8/20 monocytes and 3/20 neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. We also found evidence of somatic hypermutation of the variable (V) gene segments in AML-derived IgM gene rearrangements but not in IgM from monocytes or neutrophils from patients with non-hematopoietic neoplasms and healthy individuals. Furthermore, IgM VHμDJHμ gene rearrangements in AML cell lines, primary myeloblasts, and monocytes and neutrophils from patients with non-hematopoietic neoplasms showed a restricted V usage and repertoire, whereas the VHμDJHμ gene rearrangements in monocytes and neutrophils from healthy individuals displayed more diversity. Anti-human IgM inhibited cell proliferation, but did not induce apoptosis in AML cell lines. Our findings suggest that AML-derived IgM might be a novel AML-related molecule that is involved in leukemogenesis and AML progression and might serve as a useful molecular marker for designing targeted therapy and monitoring minimal residual disease.Cellular & Molecular Immunology advance online publication, 21 October 2013; doi:10.1038/cmi.2013.45.
    Cellular & molecular immunology 10/2013; · 3.42 Impact Factor
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    ABSTRACT: Surface properties, as well as inherent physicochemical properties, of the engineered nanomaterials play important roles in their interactions with the biological systems, which eventually affect their efficiency in diagnostic and therapeutic applications. Here we report a new class MRI contrast agent based on milk casein protein coated iron oxide nanoparticles (CNIOs) with a core size of 15 nm and hydrodynamic diameter ~30 nm. These CNIOs exhibited excellent water-solubility, colloidal stability, and biocompatibility. Importantly, CNIOs exhibited prominent T2 enhancing capability with a transverse relaxivity r2 of 273 mM(-1)s(-1) at 3 Tesla. The transverse relaxivity is ~2.5-fold higher than that of iron oxide nanoparticles with the same core but an amphiphilic polymer coating. CNIOs showed pH-responsive properties, formed loose and soluble aggregates near the pI (pH~4.0). The aggregates could be dissociated reversibly when the solution pH was adjusted away from the pI. The transverse relaxation property and MRI contrast enhancing effect of CNIOs remained unchanged in the pH range of 2.0 to 8.0. Further functionalization of CNIOs can be achieved via surface modification of the protein coating. Bio-affinitive ligands, such as a single chain fragment from the antibody of epidermal growth factor receptor (ScFvEGFR), could be readily conjugated onto the protein coating, enabling specific targeting to MDA-MB-231 breast cancer cells over-expressing EGFR. T2-weighted MRI of mice intravenously administered with CNIOs demonstrated strong contrast enhancement in the liver and spleen. These favorable properties suggest CNIOs as a class of biomarker targeted magnetic nanoparticles for MRI contrast enhancement and related biomedical applications.
    ACS Applied Materials & Interfaces 04/2013; · 5.90 Impact Factor
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    ABSTRACT: Antifouling magnetic iron oxide nanoparticles (IONPs) coated with block copolymer poly(ethylene oxide)-block-poly(γ-methacryloxypropyltrimethoxysilane) (PEO-b-PγMPS) were investigated for improving cell targeting by reducing nonspecific uptake. Conjugation of a HER2 antibody, Herceptin®, or a single chain fragment (ScFv) of antibody against epidermal growth factor receptor (ScFvEGFR) to PEO-b-PγMPS-coated IONPs resulted in HER2-targeted or EGFR-targeted IONPs (anti-HER2-IONPs or ScFvEGFR-IONPs). The anti-HER2-IONPs bound specifically to SK-BR-3, a HER2-overexpressing breast cancer cell line, but not to MDA-MB-231, a HER2-underexpressing cell line. On the other hand, the ScFvEGFR-IONPs showed strong reactivity with MDA-MB-231, an EGFR-positive human breast cancer cell line, but not with MDA-MB-453, an EGFR-negative human breast cancer cell line. Transmission electron microscopy revealed internalization of the receptor-targeted nanoparticles by the targeted cancer cells. In addition, both antibody-conjugated and non-antibody-conjugated IONPs showed reduced nonspecific uptake by RAW264.7 mouse macrophages in vitro. The developed IONPs showed a long blood circulation time (serum half-life 11.6 hours) in mice and low accumulation in both the liver and spleen. At 24 hours after systemic administration of ScFvEGFR-IONPs into mice bearing EGFR-positive breast cancer 4T1 mouse mammary tumors, magnetic resonance imaging revealed signal reduction in the tumor as a result of the accumulation of the targeted IONPs.
    International Journal of Nanomedicine 01/2013; 8:3781-3794. · 4.20 Impact Factor
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    ABSTRACT: PURPOSE To develop an enhanced drug delivery system to liver tumors using novel MRI traceable iron oxide nanoparticles (IONP) loaded with doxorubicin and to investigate biodistribution of delivered nanoparticles by assessing intratumoral and normal liver tissue concentrations after targeted (IA) versus systemic (IV) administration. METHOD AND MATERIALS Paramagnetic IONP (core and hydrodynamic size of 10 nm and 23 nm, respectively) coated with amphiphilic polymers were non-covalently loaded with hydrophobic doxorubicin; whose presence was confirmed by optical absorption spectrum. VX2 liver tumors were induced in the left lobe of 16 rabbits, allowed to grow for 2 weeks to a size of 2 cm, and were subsequently divided into 2 treatment groups, each receiving 1 mg/kg body weight of doxorubicin via IONP. Group 1 received IA administration to the left hepatic artery under fluoroscopy, and Group 2 received IV administration via the marginal ear vein. Animals were sacrificed 3 and 24 hours after treatment. Tumor and liver sections were collected and iron concentrations of tumor and liver tissues were determined by the colorimetric method with iron binding 1,10-phenanthroline at 508 nm. Analysis of tissue iron concentrations in different groups was performed using a standard t-test, with p<0.05 considered significant. RESULTS Intratumoral and peritumoral concentrations of IONP at 3 and 24 hours post treatment were significantly higher after IA administration compared to IV (1.54 vs 1.03 mg Fe/g , p=0.019), given at the same dosage. Additionally, 24 hours after treatment, the group receiving IA therapy showed significantly higher nanoparticle concentrations in the left hepatic lobe in comparison to the IV group (1.63 vs 1.34 mg Fe/g, p=0.0226). CONCLUSION Targeted IA delivery enhances intratumoral and peritumoral uptake of IONP when compared to IV. Furthermore, tumoral levels remain significantly high up to 24 hours after targeted IA adminstration. CLINICAL RELEVANCE/APPLICATION Targeted intraarterial delivery of iron oxide nanoparticles carrying doxorubincin can serve as a powerful tool in the delivery chemotherapy drugs to liver tumors.
    Radiological Society of North America 2012 Scientific Assembly and Annual Meeting; 11/2012
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    ABSTRACT: The purpose of this study was to synthesize, characterize and tailor the surface properties of magnetic nanoparticles with biocompatible copolymer coatings and to evaluate the efficiency of the resulting nanoconjugates as magnetic resonance imaging (MRI) contrast agents for liver imaging. Magnetic nanoparticles with core diameters of 10 and 30 nm were synthesized by pyrolysis and were subsequently coated with a copolymer containing either carboxyl (SHP) or methoxy groups as termini. All four formulas, and ferumoxides (Feridex I.V.(®)), were individually injected intravenously into separate, normal Balb/C mice (at 2.5, 1.0 and 0.56 mg Fe kg(-1)), and the animals underwent T(2)-weighted MRI at multiple time points post injection (p.i.) to evaluate the hepatic uptake and clearance. Furthermore, we compared the abilities of the new formulas and Feridex to detect tumors in an orthotropic Huh7 tumor model. Transmission electron microscopy (TEM) revealed a narrow size distribution of both the 10 and 30 nm nanoparticles, in contrast to a wide size distribution of Feridex. MTT, apoptosis and cyclin/DNA flow cytometry assays showed that the polymer coated nanoparticles had no adverse effect on cell growth. Among all the tested formulas, including Feridex, SHP-30 showed the highest macrophage uptake at the in vitro level. In vivo MRI studies on normal mice confirmed the superiority of SHP-30 in inducing hypointensities in the liver tissue, especially at clinical dose (0.56 mg Fe kg(-1)) and 3 T field. SHP-30 showed better contrast-to-noise ratio than Feridex on the orthotropic Huh7 tumor model. SHP-30 was found to be an efficient contrast agent for liver MR imaging. The success of this study suggests that, by improving the synthetic approach and by tuning the surface properties of IONPs, one can arrive at better formulas than Feridex for clinical practice.
    Contrast Media & Molecular Imaging 07/2012; 7(4):363-72. · 2.87 Impact Factor
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    ABSTRACT: Human transcriptional adaptor hADA2a is an important component of the general control nonderepressible 5 (GCN5) histone acetyltransferase complex. Here, we report that coiled-coil domain containing 134 (CCDC134), a novel nuclear protein, binds to hADA2a and enhances the stability of the hADA2a protein in unstressed conditions. Furthermore, CCDC134 was found to participate in the p300/CBP-associated factor (PCAF) complex via hADA2a and affect the histone acetyltransferase activity of the complex. We also found that CCDC134 increased the PCAF-dependent K320 acetylation of p53 and p53 protein stability in the presence of hADA2a overexpression. Moreover, we demonstrated the biological significance of the interaction between CCDC134 and hADA2a. CCDC134 showed obvious nuclear accumulation after ultraviolet (UV) irradiation, and the knockdown of endogenous CCDC134 suppressed hADA2a-induced cell apoptosis activity and G1/S cell cycle arrest. Together, our findings indicate that CCDC134 might act as a novel regulator of hADA2a, and plays roles in the PCAF complex via hADA2a to affect its acetyltransferase activity and UV-induced DNA damage repair.
    Histochemie 05/2012; 138(1):41-55. · 2.61 Impact Factor
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    ABSTRACT: Engineering and functionalizing magnetic nanoparticles have been an area of the extensive research and development in the biomedical and nanomedicine fields. Because their biocompatibility and toxicity are well investigated and better understood, magnetic nanoparticles, especially iron oxide nanoparticles, are better suited materials as contrast agents for magnetic resonance imaging (MRI) and for image-directed delivery of therapeutics. Given tunable magnetic properties and various surface chemistries from the coating materials, most applications of engineered magnetic nanoparticles take advantages of their superb MRI contrast enhancing capability as well as surface functionalities. It has been found that MRI contrast enhancement by magnetic nanoparticles is highly dependent on the composition, size and surface properties as well as the degree of aggregation of the nanoparticles. Therefore, understanding the relationships between these intrinsic parameters and the relaxivities that contribute to MRI contrast can lead to establishing essential guidance that may direct the design of engineered magnetic nanoparticles for theranostics applications. On the other hand, new contrast mechanism and imaging strategy can be developed based on the novel properties of engineered magnetic nanoparticles. This review will focus on discussing the recent findings on some chemical and physical properties of engineered magnetic nanoparticles affecting the relaxivities as well as the impact on MRI contrast. Furthermore, MRI methods for imaging magnetic nanoparticles including several newly developed MRI approaches aiming at improving the detection and quantification of the engineered magnetic nanoparticles are described.
    Theranostics 01/2012; 2(1):86-102. · 7.81 Impact Factor
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    ABSTRACT: It is well known that B-1 B cells are the main cell type that is responsible for the production of natural immunoglobulin M (IgM) and can respond to infection by increasing IgM secretion. However, we unexpectedly found that some epithelial cells also can express rearranged IgM transcript that has natural IgM characteristics, such as germline-encoded and restricted rearrangement patterns. Here we studied IgM expression in human non-B cells and found that IgM was frequently expressed by many human epithelial cancer cells as well as non-cancer epithelial cells. Moreover, CD79A and CD79B, two molecules that are physically linked to membranous IgM on the surface of B cells to form the B cell antigen receptor complex, were also expressed on the cell surface of epithelial cancer cells and co-located with IgM. Like the natural IgM, the epithelial cancer cell-derived IgM recognized a series of microbial antigens, such as single-stranded DNA, double-stranded DNA, lipopolysaccharide, and the HEp-2 cell antigen. More important, stimulation of the toll-like receptor 9 (TLR9), which mimics bacterial infection, substantially increased the secretion of IgM in human epithelial cancer cells. These findings indicate that human epithelial cancer cells as well as non-cancer epithelial cells can spontaneously produce IgM with natural antibody activity.
    PLoS ONE 01/2012; 7(12):e51423. · 3.53 Impact Factor
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    Biomedical Engineering - From Theory to Applications, 08/2011; , ISBN: 978-953-307-637-9
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    ABSTRACT: The effect of nanoparticle size (30-120 nm) on magnetic resonance imaging (MRI) of hepatic lesions in vivo has been systematically examined using polyvinylpyrrolidone (PVP)-coated iron oxide nanoparticles (PVP-IOs). Such biocompatible PVP-IOs with different sizes were synthesized by a simple one-pot pyrolysis method. These PVP-IOs exhibited good crystallinity and high T(2) relaxivities, and the relaxivity increased with the size of the magnetic nanoparticles. It was found that cellular uptake changed with both size and surface physiochemical properties, and that PVP-IO-37 with a core size of 37 nm and hydrodynamic particle size of 100 nm exhibited higher cellular uptake rate and greater distribution than other PVP-IOs and Feridex. We systematically investigated the effect of nanoparticle size on MRI of normal liver and hepatic lesions in vivo. The physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their ability to accumulate in the liver. The contrast enhancement of PVP-IOs within the liver was highly dependent on the overall size of the nanoparticles, and the 100 nm PVP-IO-37 nanoparticles exhibited the greatest enhancement. These results will have implications in designing engineered nanoparticles that are optimized as MR contrast agents or for use in therapeutics.
    ACS Nano 11/2010; 4(12):7151-60. · 12.03 Impact Factor
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    ABSTRACT: We report in this Communication a facile, two-step surface modification strategy to achieve manganese oxide nanoparticles with prominent MRI T1 contrast. In a U87MG glioblastoma xenograft model, we confirmed that the particles can accumulate efficiently in tumor area to induce effective T1 signal alteration.
    Chemical Communications 09/2010; 46(36):6684-6. · 6.38 Impact Factor
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    ABSTRACT: The restriction of immunoglobulin (Ig) expression to B lymphocytes is well established. However, several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells. Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression. Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines. Moreover, two novel positive regulatory elements, an enhancer-like element at -800 to -610 bp and a copromoter-like element at -610 to -300 bp, were identified in two epithelial cancer cell lines, HeLa S3 and HT-29. The octamer element (5'-ATGCAAAT-3') located in the Ig promoter, a crucial element for B-cell-derived Ig gene transcription, was also very important for non-B-cell-derived Ig gene transcription. More importantly, we confirmed that octamer-related protein-1 (Oct-1), but not Oct-2, was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells. These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells.
    Cellular & molecular immunology 07/2010; 7(4):279-86. · 3.42 Impact Factor
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    ABSTRACT: Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the buildup of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with (64)Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area.
    Biomaterials 04/2010; 31(11):3016-22. · 8.31 Impact Factor

Publication Stats

375 Citations
116.05 Total Impact Points

Institutions

  • 2012–2014
    • Emory University
      • Department of Radiology and Imaging Sciences
      Atlanta, Georgia, United States
    • Peking University People's Hospital
      Peping, Beijing, China
    • Harbin Medical University
      Charbin, Heilongjiang Sheng, China
  • 2007–2013
    • Peking University
      • • School of Basic Medical Science
      • • Center for Human Disease Genomics
      • • College of Chemistry and Molecular Engineering
      Peping, Beijing, China
  • 2010
    • National Eye Institute
      Maryland, United States
    • Beijing University of Technology
      Peping, Beijing, China
    • Stanford University
      • Department of Radiology
      Stanford, CA, United States
  • 2008
    • Peking University Health Science Center
      Peping, Beijing, China