title: Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors.
abstract: The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid- and polymeric-vesicle-based nanoreactors have some practical limitations. We have succeeded in preparing enzyme-loaded polyion complex vesicles (PICsomes) through a facile protein-loading method. The preservation of enzyme activity was confirmed even after cross-linking of the PICsomes. The cross-linked β-galactosidase-loaded PICsomes (β-gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER-βGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the β-gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme-loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.
authors.affiliation: Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Anraku
authors.affiliation: Faculty of Engineering, Center for Molecular Systems (CMS), Kyushu University, 744, Moto-oka, Nishi-ku, Fukuoka, 819-0395 (Japan). kishimura@mail.cstm.kyushu-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.affiliation: Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Mako
authors.initials: M
authors.lastname: Kamiya
authors.affiliation: Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 (Japan).
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan).
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nomoto
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Kazuko
authors.initials: K
authors.lastname: Toh
authors.affiliation: Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Yu
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/
authors.forename: Daiki
authors.initials: D
authors.lastname: Sueyoshi
authors.affiliation: Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530 (Japan).
authors.forename: Mitsunobu R
authors.initials: MR
authors.lastname: Kano
authors.affiliation: 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: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan).
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan) http://www.bmw.t.u-tokyo.ac.jp/. kataoka@bmw.t.u-tokyo.ac.jp.|Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033 (Japan). kataoka@bmw.t.u-tokyo.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D019149:Bioreactors; D002850:Chromatography, Gel; D004798:Enzymes / Q000008:administration & dosage*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D009374:Neoplasms, Experimental / Q000378:metabolism*
chemical_list: D004798:Enzymes
keywords: drug delivery; enzymes; in vivo imaging; nanoreactors; vesicles