Hyaluronic Acid–Gold Nanoparticle/Interferon α Complex for Targeted Treatment of Hepatitis C Virus Infection

Lee, Min Young; Yang, Jeong A.; Jung, Ho Sang; Beack, Songeun; Choi, Jung Eun; Hur, Wonhee; Koo, Heebeom; Kim, Kwangmeyung; Yoon, Seung Kew; Hahn, Sei Kwang

doi:10.1021/nn302538y

Cited by 148 publications

(126 citation statements)

References 34 publications

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“…There are also examples from the literature where multivalent conjugation to HyA has been shown to maintain an effective serum concentration of protein-based drugs after systemic administration, 79,80 yielding an improvement in their pharmacokinetics that was comparable to PEGyation. 81 By contrast, in this study, we applied the mvShh treatments locally and were unable to separate the multivalency advantage from any other in vivo advantages of conjugation to a long-chain biopolymer.…”

Section: Discussionmentioning

confidence: 76%

Multivalent Conjugates of Sonic Hedgehog Accelerate Diabetic Wound Healing

Han

Layman

Rode

et al. 2015

Tissue Engineering Part A

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Despite their preclinical promise, few recombinant growth factors have been fully developed into effective therapies, in part, due to the short interval of therapeutic activity after administration. To address this problem, we developed nanoscale polymer conjugates for multivalent presentation of therapeutic proteins that enhance the activation of targeted cellular responses. As an example of this technology, we conjugated multiple Sonic hedgehog (Shh) proteins onto individual hyaluronic acid biopolymers to generate multivalent protein clusters at defined ratios (i.e., valencies) that yield enhanced Shh pathway activation at equivalent concentrations relative to unconjugated Shh. In this study, we investigated whether these multivalent conjugates (mvShh) could be used to improve the therapeutic function of Shh. We found that a single treatment with mvShh significantly accelerated the closure of full-thickness wounds in diabetic (db/db) mice compared to either an equivalent dose of unconjugated Shh or the vehicle control. Furthermore, we identified specific indicators of wound healing in fibroblasts and endothelial cells (i.e., transcriptional activation and cell migration) that were activated by mvShh in vitro and at concentrations approximately an order of magnitude lower than the unconjugated Shh. Taken together, our findings suggest that mvShh conjugates exhibit greater potency to activate the Shh pathway, and this multivalency advantage improves its therapeutic effect to accelerate wound closure in a diabetic animal model. Our strategy of multivalent protein presentation using nanoscale polymer conjugates has the potential to make a significant impact on the development of protein-based therapies by improving their in vivo performance.

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Section: Discussionmentioning

confidence: 76%

Multivalent Conjugates of Sonic Hedgehog Accelerate Diabetic Wound Healing

Han

Layman

Rode

et al. 2015

Tissue Engineering Part A

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“…As a target-specific drug delivery carrier, HA has been investigated well in the HA receptor-mediated endocytosis because of its polyanionic characteristics and hydrophilicity, 32 and highly efficient targeted delivery to target sites with HA receptors, such as CD44, HARE, and LYVE-1, for various biological functions. 33,34 According to over-mentioned intensive reports, we chose HA as a targeting ligand to synthesize the HA-Bi 2 O 3 NPs as a multifunctional theranostic platform that can afford spatialand temporal-specific CT imaging and enable overcoming cancer radioresistance. This specifically developed tumortargeted probe holds a great promise as a CT imaging CA with better CT imaging quality at reduced CA dosage when compared with the currently available CAs imaged using a clinical CT scanner.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-functionalized bismuth oxide nanoparticles for computed tomography imaging-guided radiotherapy of tumor

Lou

Jiang

et al. 2017

IJN

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The inherent radioresistance and inaccuracy of localization of tumors weaken the clinical implementation effectiveness of radiotherapy. To overcome these limitations, hyaluronic acid-functionalized bismuth oxide nanoparticles (HA-Bi 2 O 3 NPs) were synthesized by one-pot hydrothermal method for target-specific computed tomography (CT) imaging and radiosensitization of tumor. After functionalization with hyaluronic acid, the Bi 2 O 3 NPs possessed favorable solubility in water and excellent biocompatibility and were uptaken specifically by cancer cells overexpressing CD44 receptors. The as-prepared HA-Bi 2 O 3 NPs exhibited high X-ray attenuation efficiency and ideal radiosensitivity via synergizing X-rays to induce cell apoptosis and arrest the cell cycle in a dose-dependent manner in vitro. Remarkably, these properties offered excellent performance in active-targeting CT imaging and enhancement of radiosensitivity for inhibition of tumor growth. These findings demonstrated that HA-Bi 2 O 3 NPs as theranostic agents exhibit great promise for CT imaging-guided radiotherapy in diagnosis and treatment of tumors.

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“…HA-IFN-GNPs of 22 nm showed preferential accumulation in liver and remained in the liver upto 7 days postinjection, as measured by 2´-5´ oligoadenylate synthetase expression. As compared with IFN-GNPs, greater therapeutic efficacy of HA-IFN-GNPS was found to be associated with enhanced serum stability of the later [61].…”

Section: Pullulan-based Nanoparticlesmentioning

confidence: 93%

Carbohydrate-Based Materials for Targeted Delivery of Drugs and Genes to the Liver

Ahmed

Narain

2015

Nanomedicine (Lond.)

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The insult to liver by toxic materials leads to cirrhosis, hepatitis and cancer. Upon administration, drugs accumulate in liver, which is systemically cleared by reticuloendothelial system. However, specific targeting of drugs to liver is a serious challenge. Specific delivery of molecules to hepatocytes is accomplished by targeting cell surface lectins, asialoglycoprotein receptors. Asialofetuin, N-acetyl glucosamine and galactose are high-affinity ligands of asialoglycoprotein receptors. The bioconjugation of drugs, fluorescent molecules and gene delivery vectors with lectin-targeting agents, and their delivery in liver hepatocytes, is discussed. Mannose and N-acetyl glucosamine conjugates are evaluated for their delivery to hepatic stellate and kupffer cells. The glycosylated gene and drug delivery vectors in clinical trials are outlined.

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Hyaluronic Acid–Gold Nanoparticle/Interferon α Complex for Targeted Treatment of Hepatitis C Virus Infection

Cited by 148 publications

References 34 publications

Multivalent Conjugates of Sonic Hedgehog Accelerate Diabetic Wound Healing

Multivalent Conjugates of Sonic Hedgehog Accelerate Diabetic Wound Healing

Hyaluronic acid-functionalized bismuth oxide nanoparticles for computed tomography imaging-guided radiotherapy of tumor

Carbohydrate-Based Materials for Targeted Delivery of Drugs and Genes to the Liver

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