Hong Ding

Publications (55) View all

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  Available from: Hong Ding

  Article: Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications.

  Folarin Erogbogbo, Ching-Wen Chang, Jasmine L May, Liwei Liu, Rajiv Kumar, Wing-Cheung Law, Hong Ding, Ken Tye Yong, Indrajit Roy, Mukund Sheshadri, Mark T Swihart, Paras N Prasad
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  ABSTRACT: Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd³⁺) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd³⁺. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM⁻¹ s⁻¹ (in terms of Gd³⁺ concentration), calculated to be around 6000 mM⁻¹ s⁻¹ per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.
  Nanoscale 08/2012; 4(17):5483-9. · 5.91 Impact Factor
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  Article: Increasing TNF levels solely in the rat hippocampus produces persistent pain-like symptoms.

  Regina T Martuscello, Robert N Spengler, Adela C Bonoiu, Bruce A Davidson, Jadwiga Helinski, Hong Ding, Supriya Mahajan, Rajiv Kumar, Earl J Bergey, Paul R Knight, Paras N Prasad, Tracey A Ignatowski
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  ABSTRACT: The manifestation of chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). Previously, we have shown that the hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation. Using an animal model of peripheral neuropathic pain, we have demonstrated that intracerebroventricular infusion of a TNF antibody adjacent to the hippocampus completely alleviated pain. Furthermore, intracerebroventricular infusion of rTNF adjacent to the hippocampus induced pain behavior in naïve animals similar to that expressed during a model of neuropathic pain. These data support our premise that enhanced production of hippocampal-TNF is integral in pain sensation. In the present study, TNF gene expression was induced exclusively in the hippocampus, eliciting increased local bioactive TNF levels, and animals were assessed for pain behaviors. Male Sprague-Dawley rats received stereotaxic injection of gold nanorod (GNR)-complexed cDNA (control or TNF) plasmids (nanoplasmidexes), and pain responses (i.e., thermal hyperalgesia and mechanical allodynia) were measured. Animals receiving hippocampal microinjection of TNF nanoplasmidexes developed thermal hyperalgesia bilaterally. Sensitivity to mechanical stimulation also developed bilaterally in the rat hind paws. In support of these behavioral findings, immunoreactive staining for TNF, bioactive levels of TNF, and levels of TNF mRNA per polymerase chain reaction analysis were assessed in several brain regions and found to be increased only in the hippocampus. These findings indicate that the specific elevation of TNF in the hippocampus is not a consequence of pain, but in fact induces these behaviors/symptoms.
  Pain 07/2012; 153(9):1871-82. · 5.78 Impact Factor
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  Article: Noninvasive real-time fluorescence imaging of the lymphatic uptake of BSA-IRDye 680 conjugate administered subcutaneously in mice.

  Fang Wu, Suraj G Bhansali, Mitalee Tamhane, Rajiv Kumar, Lisa A Vathy, Hong Ding, Ken-Tye Yong, Earl J Bergey, Paras N Prasad, Marilyn E Morris
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  ABSTRACT: The goal of our studies was to determine lymphatic uptake of bovine serum albumin (BSA) using real-time noninvasive fluorescence imaging. BSA labeled with near-infrared dye (IRDye) 680 was used as a model protein-dye conjugate. The conjugation of BSA with IRDye 680 was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Size-exclusion high-performance liquid chromatography and SDS-PAGE demonstrated that the IRDye 680-labeled BSA conjugate in the lymph node (LN) homogenate samples was stable at physiological temperature (37°C) for at least 5 days. Whole-body noninvasive optical imaging of hairless SKH-1 mice was performed after subcutaneous (s.c.) injection (dose = 0.1 mg/kg) into the front footpad. Noninvasive fluorescence imaging demonstrated that BSA-IRDye 680 conjugates were dynamically taken up by the lymphatic system, accumulated in the axillary LNs and then cleared, indicating that lymphatic transport plays a role in the absorption of BSA. Ex vivo tissue imaging of LN homogenates provided confirmatory data with respect to the uptake of fluorescent-labeled BSA determined by in vivo imaging. Noninvasive real-time imaging of LNs provides a novel tool for evaluating uptake and accumulation of fluorescent-labeled proteins by the lymphatic system after s.c. injection in a mouse model.
  Journal of Pharmaceutical Sciences 01/2012; 101(5):1744-54. · 3.06 Impact Factor
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  Article: Image guided biodistribution and pharmacokinetic studies of theranostics.

  Hong Ding, Fang Wu
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  ABSTRACT: Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drug delivery systems in various diseases, especially cancers. Besides anatomical imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), molecular imaging strategy including optical imaging, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) will facilitate the localization and quantization of radioisotope or optical probe labeled nanoparticle delivery systems in the category of theranostics. The quantitative measurement of the bio-distribution and pharmacokinetics of theranostics in the fields of new drug/probe development, diagnosis and treatment process monitoring as well as tracking the brain-blood-barrier (BBB) breaking through by high sensitive imaging method, and the applications of the representative imaging modalities are summarized in this review.
  Theranostics. 01/2012; 2(11):1040-53.
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  Article: Cholesterol derivatives based charged liposomes for Doxorubicin delivery: preparation, in vitro and in vivo characterization.

  Yu Nie, Li Ji, Hong Ding, Li Xie, Li Li, Bin He, Yao Wu, Zhongwei Gu
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  ABSTRACT: Cholesterol plays a critical role in liposome composition. It has great impact on the behavior of liposome in vitro and in vivo. In order to verify the possible effects from cholesterol charge, surface shielding and chemical nature, two catalogs of liposomes with charged and PEGylated cholesterols were synthesized. Anionic liposomes (AL) and cationic liposomes (CL) were prepared, with charges from hemisuccinate and lysine in cholesterol derivatives, respectively. Characteristics of different formulated liposomes were investigated after doxorubicin encapsulation, using neutral liposomes (NL) as control. Results showed that after PEGylation, AL and CL liposomes displayed prolonged retention release profile, while kept similar size distribution, encapsulation efficiency, low cytotoxicity and hemolysis comparing with NL. Confocal laser scanning microscopy and flow cytometry experiments confirmed the significantly higher cell uptake from AL and CL vesicles than the NL in mouse breast carcinoma and melanoma cells, human epithelial carcinoma and hepatoma cells. It was in accordance with our corresponding cellular mortality studies of DOX-loaded liposomes. The in vivo anti-tumor effect experiments from charged liposomes also presented much higher tumor inhibition effect (70% vs 45%, p < 0.05) than NL liposomes. This is the first time reporting anti-cancer effect from charged cholesterol liposome with/without PEGylation. It may give deeper understanding on the liposome formulation which is critical for liposome associated drug research and development.
  Theranostics. 01/2012; 2(11):1092-103.