title: Hyaluronic acid receptor-targetable imidazolized nanovectors for induction of gastric cancer cell death by RNA interference.
abstract: 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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, College of Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Yang
authors.forename: Hyun-Ouk
authors.initials: HO
authors.lastname: Kim
authors.forename: Yonghee
authors.initials: Y
authors.lastname: An
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Lim
authors.forename: Gyudo
authors.initials: G
authors.lastname: Lee
authors.forename: Taeyun
authors.initials: T
authors.lastname: Kwon
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Cheong
authors.forename: Jin-Suck
authors.initials: JS
authors.lastname: Suh
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.forename: Seungjoo
authors.initials: S
authors.lastname: Haam
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005822:Genetic Vectors / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry*; D042541:Intracellular Space / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D055672:Static Electricity; D013274:Stomach Neoplasms / Q000473:pathology*; D014162:Transfection; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D007093:Imidazoles; D034741:RNA, Small Interfering; D051020:bcl-X Protein; D011107:Polylysine; D004247:DNA