• Journal of Microbiology and Biotechnology
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• v.20 no.4
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• pp.821-827
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• 2010

Gene delivery that provides targeted delivery of therapeutic genes to the cells of a lesion enhances therapeutic efficacy and reduces toxic side effects. This process is especially important in cancer therapy when it is advantageous to avoid unwanted damage to healthy normal cells. Incorporating cancer-specific ligands that recognize receptors overexpressed on cancer cells can increase selective binding and uptake and, as a result, increase targeted transgene expression. In this study, we investigated whether a peptide capable of homing to hepatocellular carcinoma (HCC) could facilitate targeted gene delivery by cationic liposomes. This homing peptide (HBP) exhibited selective binding to a human hepatocarcinoma cell line, HepG2, at a concentration ranging from 5 to 5,000 nM. When conjugated to a cationic liposome, HBP substantially increased cellular internalization of plasmid DNA to increase the transgene expression in HepG2 cells. In addition, there was no significant enhancement in gene transfer detected for other human cell lines tested, including THLE-3, AD293, and MCF-7 cells. Therefore, we demonstrate that HBP provides targeted gene delivery to HCC by cationic liposomes.

• Macromolecular Research
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• v.15 no.2
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• pp.100-108
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• 2007

Gene therapy has become a promising strategy for the treatment of genetically based diseases, such as cancer, which are currently considered incurable. A major obstacle in the field of cancer gene therapy is the development of a safe and efficient delivery system for therapeutic gene transfer. Non-viral vectors have attracted great interest, as they are simple to prepare, stable, easy to modify and relatively safe compared to viral vectors. In this review, an insight into the strategies developed for polyethylenimine (PEI)-based non-viral vectors has been provide, including improvement of the polyplex properties by incorporating hydrophilic spacer, poly(ethylene glycol) (PEG). Moreover, this review will summarize the strategies for the tumor targeting. Specifically, a targeted polymeric gene delivery system, PEI-g-PEG-RGD, will be introduced as an efficient gene delivery vector for tumor therapy, including its functional analysis both in vitro and in vivo.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.1-15
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• 2001

Gene therapy has emerged as a new concept of therapeutic strategies to treat diseases which do not respond to the conventional therapies. The principle of gene therapy is to Introduce genetic materials into patient cells to produce therapeutic proteins in these cells. Gene therapy is now at the stage where a number of clinical trials have been carried out to patients with gene-deficiency disease or cancer. Genetic materials for gene therapy are generally composed of gene expression system and gene delivery system. For the clinical application of gene therapy in a way which conventional drugs are used, researches have been focused on the design of gene delivery system which can offer high transfection efficiency with minimal toxicity. Currently, viral delivery systems generally provide higher transfection efficiency compared with non-viral delivery systems while non-viral delivery systems are less toxic, less immunogenic and manufacturable in large scale compared with viral systems. Recently, novel strategies towards the design of new non-viral delivery system, combination of viral and non-viral delivery systems and targeted delivery system have been extensively studied. The continued effort in this area will lead us to develop gene medicine as "gene as a drug" in the near future.

• Journal of Microbiology and Biotechnology
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• v.24 no.9
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• pp.1291-1299
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• 2014

Recently, multifunctional nanomaterials have been developed as nanotherapeutic agents for cellular imaging and targeted cancer treatment because of their ease of synthesis and low cytotoxicity. In this study, we developed a multifunctional, two-component nanorod consisting of gold (Au) and nickel (Ni) blocks that enables dual-fluorescence imaging and the targeted delivery of small interfering RNA (siRNA) to improve cancer treatment. Fluorescein isothiocyanate-labeled luteinizing hormone-releasing hormone (LHRH) peptides were attached to the surface of a Ni block via a histidine-tagged LHRH interaction to specifically bind to a breast cancer cell line, MCF-7. The Au block was modified with TAMRA-labeled thiolated siRNA in order to knock down the vascular endothelial growth factor protein to inhibit cancer growth. These two-component nanorods actively targeted and internalized into MCF-7 cells to induce apoptosis through RNA interference. This study demonstrates the feasibility of using two-component nanorods as a potential theranostic in breast cancer treatment, with capabilities in dual imaging and targeted gene delivery.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.229-239
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• 2002

Recent progress in understanding the molecular basis of cancer brought out new materials such as oligonucleotides, genes, peptides and proteins as a source of new anticancer agents. Due to their macromolecular properties, however, new strategies of delivery for them are required to achieve their full therapeutic efficacy in clinical setting. Development of improved dosage forms of currently marketed anticancer drugs can also enhance their therapeutic values. Currently developed delivery systems for anticancer agents include colloidal systems (liposomes, emulsions, nanoparticles and micelles), polymer implants and polymer conjugates. These delivery systems have been able to provide enhanced therapeutic activity and reduced toxicity of anticancer agents mainly by altering their pharmacokinetics and biodistribution. Furthermore, the identification of cell-specific receptor/antigens on cancer cells have brought the development of ligand- or antibody-bearing delivery systems which can be targeted to cancer cells by specific binding to receptors or antigens. They have exhibited specific and selective delivery of anticancer agents to cancer. As a consequence of extensive research, clinical development of anticancer agents utilizing various delivery systems is undergoing worldwide. New technologies and multidisciplinary expertise to develop advanced drug delivery systems, applicable to a wide range of anticancer agents, may eventually lead to an effective cancer therapy in the future.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.651-656
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• 2012

Cationic immunoliposomes were prepared by conjugation of Fab' fragments of the recombinant humanized monoclonal antibody (HuCC49) against tumor-associated glycoprotein (TAG)-72 to sterically unilamella liposomes. The cationic immunoliposomes are composed of cationic lipid (O,O'-dimyristyl-N-lysyl aspartate, DMKD), cholesterol, and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethyleneglycol)$_{2000}$] (DPPE-PEG-maleimide) with a molar ratio of 0.5:0.47:0.03. Plasmid DNA was effectively condensed by addition of transferrin (Tf) during the formation of anti-TAG-72 PEG-immunolipoplexes (PILPs). These anti-TAG-72 PILPs were able to adhere to the surface of TAG-72-overexepressing LS174T human colon cancer cells more effectively than conventional liposomes, thereby facilitating gene delivery in vitro. Furthermore, intravenous administration of the anti-TAG-72 PILPs into the tumor-carrying mice exhibited efficient localization of the reporter gene in the tumor tissues.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.315.2-316
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• 2003

Polyethylenimine (PEI) has been used as a non-viral gene delivery carrier. To improve the efficacy of transfection, transferrin was incorporated by covalent linkage to PEI. As a model plasmid DNA, pHME185/b-gal, a mammalian expression vector was used. The transferrin-polyethylenimine (TfPEI) was synthesized by conjugate PEI with transferrin using sodium periodateand and characterized by FT-IR and 1H-NMR. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.427.1-427.1
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• 2002

To improve stability and transfection efficiency, a novel combination of cationic emulsion and galactosylated chitosan was developed for targeted gene delivery. Six formulations of cationic liposome and our novel emulsion were prepared for comparison of stability and transfection efficiency. Cationic liposomes composed of 3［N-(N.N dimethylaminoethylene) carbamoyl］ cholesterol (DC-Chol) and dioleyl phophatidyl ethanolamine (DOPE) were prepared by extrusion method and cationic emulsions composed of DC-Chol. DOPE. castor oil, and Tween 80 were prepared by sonication method. (omitted)

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.230.3-231
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• 2001

• Polymer(Korea)
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• v.33 no.3
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• pp.213-218
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• 2009

A cationic lipid emulsion containing 1,2-dioleoyl-3-trimethylammonium-propane(DOTAP), Tween80, squalene has been prepared as a gene delivery system. In order to increase the transfection efficiency of gene carrier, folate was used as the tumor-targeting ligand that was attached on PEG-DPPE. HeLa and 293 cells were used for the in vitro transfection experiment. HeLa cell is a folate-positive cell line. The mean particle sizes of polymeric lipid system and DNA/lipid complex system were 206.6 nm and 150.5 nm, respectively. The transfection efficiencies of our carriers(4:l(w:w) complex ratio)were 100 times higher than that of DOTAP only emulsion due to the targeting effect of folate.