title: Polyplex Micelles with Double-Protective Compartments of Hydrophilic Shell and Thermoswitchable Palisade of Poly(oxazoline)-Based Block Copolymers for Promoted Gene Transfection.
abstract: Improving the stability of polyplex micelles under physiological conditions is a critical issue for promoting gene transfection efficiencies. To this end, hydrophobic palisade was installed between the inner core of packaged plasmid DNA (pDNA) and the hydrophilic shell of polyplex micelles using a triblock copolymer consisting of hydrophilic poly(2-ethyl-2-oxazoline), thermoswitchable amphiphilic poly(2-n-propyl-2-oxazoline) (PnPrOx) and cationic poly(L-lysine). The two-step preparation procedure, mixing the triblock copolymer with pDNA below the lower critical solution temperature (LCST) of PnPrOx, followed by incubation above the LCST to form a hydrophobic palisade of the collapsed PnPrOx segment, induced the formation of spatially aligned hydrophilic-hydrophobic double-protected polyplex micelles. The prepared polyplex micelles exhibited significant tolerance against attacks from nuclease and polyanions compared to those without hydrophobic palisades, thereby promoting gene transfection. These results corroborated the utility of amphiphilic poly(oxazoline) as a molecular thermal switch to improve the stability of polyplex gene carriers relevant for physiological applications.
authors.forename: Shigehito
authors.initials: S
authors.lastname: Osawa
authors.affiliation: Japan Science and Technology Agency, PRESTO, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Osada
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Hiki
authors.forename: Anjaneyulu
authors.initials: A
authors.lastname: Dirisala
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.|Innovation Center of NanoMedicine (iCONM), 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D004247:DNA / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010957:Plasmids / Q000235:genetics*; D011073:Polyamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D008823:Micelles; D011073:Polyamines; C511916:poly(2-ethyl-2-oxazoline); D011107:Polylysine; D011092:Polyethylene Glycols; D004247:DNA