8 results on '"Kang, Han Chang"'
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2. Bioreducible polyspermine as less toxic and efficient gene carrier.
- Author
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Park, Hongsuk, Nichols, Joseph W., Kang, Han Chang, and Bae, You Han
- Subjects
MEDICAL polymers ,PLASMIDS ,NUCLEIC acids ,THIOLS ,CELL lines ,GENE transfection - Abstract
Bioreducible polymers have attracted intense attention as a gene carrier due to their low cell toxicity compared to other polymer-based gene delivery counterparts. We have synthesized low-molecular-weight spermine-originated bioreducible polyspermines (BPSs) to serve as a plasmid DNA (pDNA) carrier complex with low cytotoxicity and high transfection efficiency. Spermine is biogenic and ubiquitous and is of benefit to nucleic acid delivery in many respects. We found that the BPSs formed nano-sized, positively charged complexes with pDNA. In addition, they showed a high buffering capacity from the polyamine-based proton sponge effect which facilitates endosomal escape. With degradable characteristics in thiol-rich (intracellular) environments, BPSs exhibited significantly improved cell viability and suitable transfection efficiency across several cell lines in comparison to linear and branched polyethylenimine, the current gold standards of non-viral gene carriers. BPSs appear to be promising polymers for use as effective pDNA carriers. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
3. Bioreducible PolymersAs a Determining Factor forPolyplex Decomplexation Rate and Transfection.
- Author
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Hwang, Hee Sook, Kang, Han Chang, and Bae, You Han
- Subjects
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CELL-mediated cytotoxicity , *GENE expression , *BIODEGRADABLE plastics , *GENE transfection , *GENETIC transformation , *CELL lines - Abstract
Polyplex formation (complexation) and gene release fromthe polyplexes(decomplexation) are major events in polymeric gene delivery; however,the effect of the decomplexation rate on transfection has been rarelyinvestigated. This study employed mixed polymers of poly(L-lysine) (PLL: MW ∼7.4 kDa) and reducible PLL (RPLL) (MW ∼6.7kDa) to design decomplexation rate-controllable PLL100–xRPLLx/pDNA complexes(PRLxpolyplexes). The transfection efficiencyof a model gene (luciferase) in MCF7 and HEK293 cell lines increasedwith increasing x(RPLL content) in the PRLxpolyplexes until peaking at x=2.5 and 10, respectively, after which point transfection efficiencydeclined rapidly. In MCF7 cells, PRL2.5polyplex produced3 or 223 times higher gene expression than PLL or RPLL polyplexes,respectively. Similarly, the transfection efficiency of PRL10polyplex-transfected HEK293 cells was 3.8 or 67 times higher thanthat of PLL or RPLL polyplexes, respectively. The transfection resultswere not apparently related to the particle size, surface charge,complexation/compactness, cellular uptake, or cytotoxicity of thetested polyplexes. However, the decomplexation rate varied by RPLLcontent in the polyplexes, which in turn influenced the gene transfection.The nuclear localization of pDNA delivered by PRLxpolyplexes showed a similar trend to their transfection efficiencies.This study suggests that an optimum decomplexation rate may resultin high nuclear localization of pDNA and transfection. Understandingin decomplexation and intracellular localization of pDNA may helpdevelop more effective polyplexes. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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4. The effect of environmental pH on polymeric transfection efficiency
- Author
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Kang, Han Chang, Samsonova, Olga, Kang, Sun-Woong, and Bae, You Han
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GENE transfection , *MEDICAL polymers , *ENDOCYTOSIS , *GENE expression , *CELL cycle , *CULTURE media (Biology) , *ACIDIFICATION - Abstract
Abstract: Although polymers, polyplexes, and cells are exposed to various extracellular and intracellular pH environments during polyplex preparation and polymeric transfection, the impact of environmental pH on polymeric transfection has not yet been investigated. This study aims to understand the influence of environmental pH on polymeric transfection by modulating the pH of the transfection medium or the culture medium. Changes in the extracellular pH affected polymeric transfection by way of complex factors such as pH-induced changes in polymer characteristics (e.g., proton buffering capacity and ionization), polyplex characteristics (e.g., size, surface charge, and decomplexation), and cellular characteristics (e.g., cellular uptake, cell cycle phases, and intracellular pH environment). Notably, acidic medium delayed endocytosis, endosomal acidification, cytosolic release, and decomplexation of polyplexes, thereby negatively affecting gene expression. However, acidic medium inhibited mitosis and reduced dilution of gene expression, resulting in increased transfection efficiency. Compared to pH 7.4 medium, acidic transfection medium reduced gene expression 1.6–7.7-fold whereas acidic culture medium enhanced transfection efficiency 2.1–2.6-fold. Polymeric transfection was affected more by the culture medium than by the transfection medium. Understanding the effects of extracellular pH during polymeric transfection may stimulate new strategies for determining effective and safe polymeric gene carriers. [Copyright &y& Elsevier]
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- 2012
- Full Text
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5. Reconstitutable charged polymeric (PLGA)2-b-PEI micelles for gene therapeutics delivery
- Author
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Mishra, Deepa, Kang, Han Chang, and Bae, You Han
- Subjects
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POLYMERS , *MICELLES , *GENE therapy , *NUCLEIC acids , *HYDROGEN-ion concentration , *PLASMIDS , *DNA , *GENE transfection , *CELL-mediated cytotoxicity - Abstract
Abstract: This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA36kDa)2-b-bPEI25kDa (PLGA MW 36 kDa, bPEI Mw 25 kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100–150 nm) and surface charge (30–40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50–100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for “reconstituted” micelle/pDNA/bPEI1.8kDa (WR 1) complexes was 16-fold higher than its “fresh” counterpart. Although transfection levels achieved using “reconstituted” micelle/pDNA/bPEI1.8kDa complexes were 3.6-fold lower than control “fresh” bPEI25kDa/pDNA (N/P 5) complexes, transfection levels were 39-fold higher than “reconstituted” bPEI25kDa/pDNA (N/P 5) complexes. The micelle/pDNA/bPEI1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications. [Copyright &y& Elsevier]
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- 2011
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6. Transfection of insulin-secreting cell line and rat islets by functional polymeric gene vector
- Author
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Kang, Han Chang and Bae, You Han
- Subjects
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GENE transfection , *INSULIN , *CELL lines , *LABORATORY rats , *ISLANDS of Langerhans , *GENETIC vectors , *MEDICAL polymers , *GENE expression - Abstract
Abstract: The use of genetically modified islets is a potential strategy for overcoming pitfalls that currently plague islet transplantation. This study employed functional polymeric vectors specifically designed to transfect insulin-secreting cells and results were compared to various non-viral vectors. The evaluation included transfection efficiency, experimental condition effects, gross morphological observation, cytotoxicity, apoptosis, gene distribution in treated islets, insulin secretion function and time-dependent gene expression pattern. Observations from this study suggest that 1) the experimental conditions for islet transfection should be optimized, 2) the cytotoxicity of sulfonylurea containing vectors differs between the RINm5F cell line and primary pancreatic islets, 3) the non-viral vectors were primarily located in the peripheral region of an islet where the initial cell toxicity/apoptosis was apparent, 4) the genetic modification of pancreatic islets with genes for secretory proteins is more feasible than for residing proteins, and 5) the gene construct selection may prolong the gene expression period and oscillating pattern as demonstrated in this study. This study provides some fundamental background information that will aid in further designing polymeric gene vectors for the optimal manipulation of pancreatic islets prior to transplantation. [Copyright &y& Elsevier]
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- 2009
- Full Text
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7. All-trans-retinoic acid (ATRA)-grafted polymeric gene carriers for nuclear translocation and cell growth control
- Author
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Park, Kyong Mi, Kang, Han Chang, Cho, Jung Kyo, Chung, Ik-Joo, Cho, Sang-Hee, Bae, You Han, and Na, Kun
- Subjects
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TRETINOIN , *POLYMERIC drug delivery systems , *REGULATION of cell growth , *POLYETHYLENE , *CELL cycle regulation , *GENE transfection , *HELA cells - Abstract
Abstract: Polyethyleneimine (PEI)-g-All-trans-retinoic acid (ATRA) (designated as PRA) was synthesized as a gene carrier. ATRA at its low concentration is known to be linked to nuclear translocation and cell cycle control (either proliferation or growth arrest) depending on its binding protein in cells. The cytotoxicity of PRA conjugates was lower than that of PEI and was gradually reduced as increasing ATRA graft ratios. The resulting nanosized and positively charged PRA/pDNA complexes showed lower transfection efficiency than the PEI/pDNA complexes (N/P=10) against NIH3T3 which is less sensitive to ATRA in cell growth and more sensitive HeLa cells. However, when a mixed gene complex of PEI and PRA was applied in an effort to reduce the ATRA contents, their NIH3T3 transfection evidenced effective nuclear translocation and induced 2- to 4-fold better transfection efficiency as compared with the PEI/pDNA complexes. When the PEI/pDNA complexes were utilized to transfect HeLa cells, free ATRA treatment reduced their cellular uptake and transfection efficiency. These findings show that the NIH3T3 cells against ATRA-mediated growth arrest would not damage the PRA-mediated transfection enhancement resulting from the facilitated nuclear translocation of polyplexes or pDNA. The more ATRA-sensitivity in growth arrest of HeLa cells would reduce the transfection efficiency of ATRA-incorporated polyplexes. The transfection capability of gene by newly synthesized PRA conjugates to cells is differentiated by their ATRA-sensitivity to nuclear translocation and cell growth control. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
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8. Reducible ATP polymers as endosomolytic and bioenergetic sources in non-viral gene delivery.
- Author
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Cho, Hana and Kang, Han Chang
- Subjects
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GENE delivery techniques , *ADENOSINE triphosphate , *DRUG carriers , *GENE transfection , *MEDICAL polymers , *GENE therapy - Published
- 2017
- Full Text
- View/download PDF
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