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Hyaluronic acid receptor-targetable imidazolized nanovectors for induction of gastric cancer cell death by RNA interference

 Eunjung Kim  ;  Jaemoon Yang  ;  Hyun-Ouk Kim  ;  Yonghee An  ;  Eun-Kyung Lim  ;  Gyudo Lee  ;  Taeyun Kwon  ;  Jae-Ho Cheong  ;  Jin-Suck Suh  ;  Yong-Min Huh  ;  Seungjoo Haam 
 BIOMATERIALS, Vol.34(17) : 4327-4338, 2013 
Journal Title
Issue Date
Cell Death/drug effects ; Cell Line, Tumor ; Cell Proliferation ; DNA/metabolism ; Electrophoretic Mobility Shift Assay ; Genetic Vectors/metabolism* ; Humans ; Hyaluronan Receptors/metabolism* ; Hydrogen-Ion Concentration ; Imidazoles/chemistry* ; Intracellular Space/metabolism ; Magnetic Resonance Spectroscopy ; Nanoparticles/chemistry* ; Particle Size ; Plasmids/metabolism ; Polylysine/chemistry ; RNA Interference* ; RNA, Small Interfering/metabolism ; Static Electricity ; Stomach Neoplasms/pathology* ; Transfection ; bcl-X Protein/metabolism
Hyaluronic acid ; Imidazole ; Buffering ; RNA interference ; Gene delivery
We have developed a nanovector consisting of hyaluronic acid (HA) and poly-l-lysine-graft-imidazole (PLI)-based polyplexes containing Bcl-xL-specific shRNA-encoding plasmid DNA (HA/PLI/pDNA) for CD44 targeted gastric cancer therapy. The prepared ternary polyplexes have a negative surface charge of −24 mV and a size of approximately 100 nm at an N/P ratio of 5 with HA/PLI molar ratio of 0.03. Gel electrophoresis and cell viability experiments demonstrated that the ternary polyplexes showed high stability and no cytotoxicity due to the anchored HA molecules on the surface of PLI/pDNA binary polyplexes. Selective cancer cell death was achieved by CD44-mediated gene delivery and the internalized gene was effectively escaped from endosomes due to the buffering capacity of imidazole groups in an acidic environment. These nanovectors may be highly efficient gene delivery tools that allow the selective destruction of metastatic gastric cancer cells.
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5. Research Institutes (연구소) > Institute for Medical Convergence (연의-생공연 메디컬융합연구소) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Suh, Jin Suck(서진석) ORCID logo https://orcid.org/0000-0001-9455-9240
Yang, Jae Moon(양재문) ORCID logo https://orcid.org/0000-0001-7365-0395
Lim, Eun Kyung(임은경)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
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