Hieu Vu-Quang

Chonnam National University, Gwangju, Gwangju, South Korea

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Publications (7)19.86 Total impact

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    ABSTRACT: The aim of this study is to prepare biocompatible and targetable nanoparticles in lymph nodes (LNs) for lymph node-specific magnetic resonance (MR) imaging. Mannan-coated superparamagnetic iron oxide nanoparticles (SPIONs) (mannan-SPION), carboxylic mannan-coated SPION (CM-SPION), and β-glucan-coated SPION (Glucan-SPION) have been developed to target antigen-presenting cells (APCs), for lymph node detection by MR imaging. In this study, mannose-polyethylene glycol (PEG) was prepared by conjugating d-mannopyranosylphenyl isothiocyanate and amine-PEG-carboxyl. The 3-aminopropyltriethoxysilane (APTES)-activated SPION and the mannose-PEG were cross-linked to produce mannose-PEG-linked SPION (Mannose-PEG-SPION). Mannose-PEG-SPION carrying mannose on the surface were assumed efficient at targeting APCs through the specific interactions of the mannose tethered on the Mannose-PEG-SPION and the mannose receptors on the antigen presenting cells. The hydrophilic PEG corona layer in the Mannose-PEG-SPION could be prevented from aggregation during the systemic circulation with accompanying enhanced specificity and minimized systemic toxicity. The accumulation of SPION in the lymph nodes led to increased negative enhancement in the MR images. In the in vivo study, rats were injected intravenously with Mannose-PEG-SPION and PEG-SPION, as a control and then tracked by MR imaging after 1h, 2h, 3h, and 24h. MR imaging on lymph nodes clearly revealed the preferential uptake of Mannose-PEG-SPION in immune cell-rich lymph nodes. The predominant accumulation of Mannose-PEG-SPION in the lymph nodes was also confirmed by Prussian blue staining. Based on these results, Mannose-PEG-SPION shows great potential for lymph node-specific MR imaging.
    02/2013; 92(2):1586-95. DOI:10.1016/j.carbpol.2012.11.011
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    ABSTRACT: Cancer gene therapy involves the replacement of missing or altered genes with healthy ones. In this paper, we have proposed tumor suppressor gene-carrying superparamagnetic iron oxide nanoparticles (SPIONs) for anti-cancer gene therapy. Thermally crosslinked SPIONs (TCL-SPIONs) were conjugated with branched polyethylenimine (PEI 1800 Da) by EDC-NHS chemistry for p53 plasmid DNA delivery. The morphology of the bPEI conjugated TCL-SPIONs (bPEI-TCL-SPION) and pDNA-loaded bPEI-TCL-SPION nanoparticles was measured using transmission electron microscopy (TEM). The particle sizes of the pDNA-loaded bPEI-TCL-SPION nanoparticles were also confirmed by dynamic light scattering, and ranged from 100 to 130 nm, depending on the molar charge ratio. The fluorescently labeled pDNA was complexed with bPEI-TCL-SPION and its intracellular internalization was investigated using confocal microscopy. The p53 plasmid-loaded bPEI-TCL-SPION nanoparticles achieved significantly higher p53 tumor suppressor gene expression and cellular viability compared to positive controls. The expressed wild-type p53 protein suppressed tumor cell proliferation as compared to the mutant control. When transgene expression of the p53 tumor suppressor gene was evaluated at the mRNA level and quantified using real-time PCR, the results were highly dependent on the molar charge ratio (N/P) as well as the cancer cell type. SPIONs internalized within cancer cells were tracked by magnetic resonance (MR) imaging. It was concluded that bPEI-TCL-SPION could be used as efficient gene delivery carriers that can be tracked by MR imaging.
    Journal of Biomedical Nanotechnology 06/2012; 8(3):361-71. DOI:10.1166/jbn.2012.1407 · 7.58 Impact Factor
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    ABSTRACT: Glucans are reported to elicit immune responses through activation of macrophages by a specific interaction of β-glucan with an immune cell-specific (1,3)-β-d-glucan receptor or Dectin-1 receptor. In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with β-glucan in order to target the immune cells residing in the metastatic liver as an aid for discriminating metastasized tumor regions from normal hepatic parenchymal tissue. The morphology of prepared β-glucan-coated SPIONs (Glu-SPIONs) was characterized with dynamic light scattering (DLS) and transmission electron microscopy (TEM). The cytotoxicity of Glu-SPIONs was analyzed and compared to that of dextran- and PVA-coated SPIONs. The uptake of Glu-SPIONs by peritoneal macrophages was also confirmed with Prussian blue staining and MRI phantom tube imaging. The in vivo uptake of Glu-SPIONs in liver and lymph nodes in a metastatic mouse liver model was tracked by MR imaging after the systemic injection. The Glu-SPIONs predominantly accumulated in the macrophages surrounding the metastatic regions of the liver thereby indicating the distribution of tumor cells in the liver. MR imaging of the Glu-SPIONs clearly revealed macro- or micro-metastasized tumor regions throughout the liver, due to the preferential uptake of Glu-SPIONs into macrophages, not tumor cells. The Glu-SPION-accumulating regions were further confirmed with H&E and Prussian blue stainings after tissue sectioning. Based on our study, we propose that Glu-SPIONs can be successfully applied for diagnosing hepatic metastasis.
    Carbohydrate Polymers 01/2012; 87(2):1159–1168. DOI:10.1016/j.carbpol.2011.08.091 · 3.92 Impact Factor
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    ABSTRACT: Positively charged superparamagnetic iron oxide nanoparticle (SPION)-loaded polymersome was prepared in order to deliver genes to the target sites, which was monitored by magnetic resonance imaging (MRI), concomitantly. The transfection efficiency in vitro was tested by treating CT-26 colon cancer cell line with luciferase-expressing plasmids/SPION complex. MRI was also used to check the detectability of SPION in vitro and in vivo. SPION-loaded polymersome, carrying genetic materials, was delivered and then accumulated at the tumor site of the murine colon cancer xenograft model after intravenous injection, possibly through a passive targeting mechanism. Clinical MRI monitored this accumulation. This result indicates that the SPION-loaded polymersomecan be applied to MR image-guided gene therapy.
    Journal of Nanoscience and Nanotechnology 08/2011; 11(8):7057-60. DOI:10.1166/jnn.2011.4861 · 1.34 Impact Factor
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    ABSTRACT: Metastatic lymph nodes (LN) originate from primary cancer cells that metastasize to the lymphatic system. It is difficult to non-invasively discriminate between metastatic LN and normal LN because of their similarities in size and shape. Magnetic resonance (MR) contrast agents are widely utilized to enhance the image contrast among different tissues. Currently available dextran-based contrast agents are non-specifically internalized by macrophages. Therefore, the aim of this study was to develop mannan-coated superparamagnetic iron oxide nanoparticles (mannan-SPION) for specific delivery to immune cells in LN by receptor-mediated endocytosis for facilitated uptake in the target cells and faster acquisition of MR images. Mannan is a water soluble polysaccharide with a high content of D-mannose residues that can be recognized by mannose receptors on activated macrophages and dendritic cells. Mannan-SPION are proven to be suitable for MRI due to their small size, excellent aqueous stability, and lower cytotoxicity. Mannan-SPION are taken up by antigen-presenting cells such as macrophages and dendritic cells, which could be confirmed by Prussian blue and fluorescent staining. In addition, mannan-SPION exhibit enhanced delivery efficiency in targeting macrophages in LN in vivo compared with polyvinyl alcohol (PVA)-SPION. More specifically, the enhancement of MRI of LN by mannan-SPION increased dramatically during the earlier stages after intravenous injection, compared with PVA-SPION as a control, which indicates the potential for successful and early detection of metastastatic LN.
    Acta Biomaterialia 07/2011; 7(11):3935-45. DOI:10.1016/j.actbio.2011.06.044 · 5.68 Impact Factor
  • Journal of Nanoscience and Nanotechnology 01/2011; · 1.34 Impact Factor
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    ABSTRACT: Detection of lymph node (LN) metastasis by magnetic resonance imaging (MRI) has obtained clinical significance for treating cancer patients. LN metastasis often happens through regional lymphatic system, leading to distal tumor formation including lungs, liver and bones. Successful imaging of small and microscopic LN metastasis provides the helpful information in deciding the therapeutic option of cancer. Mannan is a water-soluble polysaccharide having high content of D-mannose residues which can be recognized by mannose receptors on activated macrophages and dendritic cells. Mannan-coated superparamagnetic iron oxide nanoparticles (Mannan-SPION) were developed to be specifically delivered to immune cells in lymph node by receptor-mediated endocytosis. Mannan-SPION was proven to be suitable for MR imaging due to small size, excellent stability in ferrofluid, and low cytotoxicity. From the Prussian blue staining, Mannan-SPION was showed their ability to be taken up by immune cells such as macrophage and dendritic cell. In addition mannan-SPION exhibited enhanced targeted delivery efficiency to macrophages in lymph nodes in vivo compared with PVA-SPION. Especially, LN enhancement of Mannan-SPION on MRI was dramatically increased at the later stage after intravenous injection compared with PVA-SPION control, indicative of the potential to successfully detect micrometastasis in LN.
    01/2010; DOI:10.1109/NANOMED.2010.5749825