title: Enzyme-Loaded Polyion Complex Vesicles as in Vivo Nanoreactors Working Sustainably under the Blood Circulation: Characterization and Functional Evaluation.
abstract: Enzyme-loaded synthetic vesicles have attracted great attention for their feasibility to exert the efficient and prolonged functionality of loaded enzymes in harsh environments, such as in vivo. However, several issues remain regarding the optimization of their structures toward practical application. Herein, we fabricated polyion complex vesicles (PICsomes) loaded with l-asparaginase (ASNase@PICsomes) and conducted a detailed characterization to ensure their utility as nanoreactors functioning under the harsh in vivo environment of the bloodstream. ASNase@PICsomes showed 100 nm-sized monodispersed vesicular structures. Fluorescence cross-correlation spectroscopy revealed essentially no empty PICsome fraction in the product, indicating the quantitative formation of ASNase@PICsomes. Furthermore, fluorescence anisotropy measurement showed that the loaded enzymes were located essentially in the inner aqueous phase of PICsomes, being successfully segregated from the external environment. ASNase@PICsomes exhibited significantly prolonged enzymatic reaction compared with free ASNase after systemic injection into mice, corroborating their functionality as in vivo nanoreactors working under the blood circulation.
authors.affiliation: Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Sueyoshi
authors.affiliation: Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Anraku
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Toru
authors.identifier: 0000-0002-9268-6964
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
authors.affiliation: Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.|Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Policy Alternatives Research Institute, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-1709, Japan.|Innovation Center of Nanomedicine, Kawasaki Institute of Industrial Promotion , 3-25-14 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
authors.forename: Kazunori
authors.identifier: 0000-0002-8591-413X
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000596:Amino Acids / Q000097:blood; D000818:Animals; D001215:Asparaginase / Q000097:blood / Q000737:chemistry; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000097:blood* / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D009097:Multienzyme Complexes; D001215:Asparaginase