Open AccessPolyplex Micelles with Double-Protective Compartments of Hydrophilic Shell and Thermoswitchable Palisade of Poly(oxazoline)-Based Block Copolymers for Promoted Gene Transfection
Author(s) -
Shigehito Osawa,
Kensuke Osada,
Shigehiro Hiki,
Anjaneyulu Dirisala,
Takehiko Ishii,
Kazunori Kataoka
Publication year - 2015
Publication title -
biomacromolecules
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.689
H-Index - 220
eISSN - 1526-4602
pISSN - 1525-7797
DOI - 10.1021/acs.biomac.5b01456
Subject(s) - lower critical solution temperature , micelle , amphiphile , copolymer , cationic polymerization , transfection , chemistry , polymer chemistry , hydrophobic effect , oxazoline , biophysics , gene delivery , chemical engineering , polymer , aqueous solution , organic chemistry , biochemistry , gene , engineering , catalysis , biology
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.