title: Spontaneous formation of nanosized unilamellar polyion complex vesicles with tunable size and properties.
abstract: Fabrication of monodispersed, submicrometer-sized vesicles (nanosomes) that form through self-assembly possessing a thin and permeable membrane remains a significant challenge. Conventional fabrication of nanosomes through self-assembly of amphiphilic molecules often requires cumbersome processes using organic solvents combined with physical procedures (e.g., sonication, thermal treatment, and membrane filtration) to obtain unilamellar structures with a controlled size distribution. Herein, we report the first example of spontaneously formed submicrometer-sized unilamellar polyion complex vesicles (Nano-PICsomes) via self-assembly of a pair of oppositely charged PEG block aniomer and homocatiomer in an aqueous medium. Detailed dynamic light scattering and transmission electron microscopic analysis revealed that vesicle sizes can be controlled in the range of 100-400 nm with a narrow size distribution, simply by changing the total polymer concentration. Also, each Nano-PICsome was composed of a uniform single PIC membrane, the thickness of which is around 10-15 nm, regardless of its size. Fluorescence correlation spectroscopy measurement verified that Nano-PICsomes were able to encapsulate water-soluble fluorescent macromolecules in the inner water phase and release them slowly into the exterior. Moreover, cross-linking of the vesicle membrane allows tuning of permeability, enhancement in stability under physiological conditions, and preservation of size and structure even after freeze-drying and centrifugation treatment. Finally, Nano-PICsomes showed a long circulation time in the bloodstream of mice. Precise control of the particle size and structure of hollow capsules through simple aqueous self-assembly and easy modification of their properties by cross-linking is quite novel and fascinating in terms of ecological, low-cost, and low-energy fabrication processes as well as the potential utility in the biomedical arena.
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Anraku
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents; D007477:Ions / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002232:Carbocyanines; D003432:Cross-Linking Reagents; D007477:Ions; D053769:Nanocapsules; C085321:cyanine dye 5; D011092:Polyethylene Glycols