title: Self-assembled ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates for targeted gene delivery.
abstract: Nanosized polyelectrolyte complexes are attractive delivery vehicles for the transfer of therapeutic genes to diseased cells. Here we report the application of self-assembled ternary complexes constructed with plasmid DNA, branched polyethylenimine and hyaluronic acid-green tea catechin conjugates for targeted gene delivery. These conjugates not only stabilize plasmid DNA/polyethylenimine complexes via the strong DNA-binding affinity of green tea catechin, but also facilitate their transport into CD44-overexpressing cells via receptor-mediated endocytosis. The hydrodynamic size, surface charge and physical stability of the complexes are characterized. We demonstrate that the stabilized ternary complexes display enhanced resistance to nuclease attack and polyanion-induced dissociation. Moreover, the ternary complexes can efficiently transfect the difficult-to-transfect HCT-116 colon cancer cell line even in serum-supplemented media due to their enhanced stability and CD44-targeting ability. Confocal microscopic analysis demonstrates that the stabilized ternary complexes are able to promote the nuclear transport of plasmid DNA more effectively than binary complexes and hyaluronic acid-coated ternary complexes. The present study suggests that the ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates can be widely utilized for CD44-targeted delivery of nucleic acid-based therapeutics.
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
authors: Kun
authors: K
authors: Liang
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
authors: Ki Hyun
authors: KH
authors: Bae
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
authors: Fan
authors: F
authors: Lee
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
authors: Keming
authors: K
authors: Xu
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
authors: Joo Eun
authors: JE
authors: Chung
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.
authors: Shu Jun
authors: SJ
authors: Gao
authors: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore. Electronic address: mkurisawa@ibn.a-star.edu.sg.
authors: Motoichi
authors: M
authors: Kurisawa
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004705:Endocytosis; D049452:Green Fluorescent Proteins / Q000235:genetics; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D013662:Tea / Q000737:chemistry / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D018960:Hyaluronan Receptors; D013662:Tea; D049452:Green Fluorescent Proteins; D002392:Catechin; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D004247:DNA; C045651:epigallocatechin gallate
keywords: CD44 targeting; Catechin; Gene delivery; Hyaluronic acid; Ternary complex