title: Enhanced cellular uptake of lactosomes using cell-penetrating peptides.
abstract: Polymeric micelles that are composed of synthetic polymers are generally size controllable and can be easily modified for various applications. Lactosomes (A3B-type) are biodegradable polymeric micelles composed of an amphipathic polymer, including three poly(sarcosine) blocks and a poly(l-lactic acid) block. Lactosomes accumulate in tumorsin vivothrough the enhanced permeability and retention (EPR) effect, even on frequently administering them. However, lactosomes cannot be efficiently internalized by cells. To improve cellular uptake of lactosomes, cell-penetrating peptide (CPP)-modified lactosomes were prepared. Seven CPPs (including EB1 and Pep1) were used, and most of them improved the cellular uptake efficiency of lactosomes. In particular, EB1- and Pep1-modified lactosomes were efficiently internalized by cells. In addition, by using CPP-modified and photosensitizer-loaded lactosomes, we demonstrated the photoinduced killing of mammalian cells, including human cancer cells. Accumulation of the EB1-modified lactosomes in NCI-N87 tumors was shown byin vivoimaging. Thus, this study demonstrated that the CPP-modified lactosome is a promising drug carrier.
authors.affiliation: Department of Medical Bioengineering, Okayama University , Okayama 700-8530 , Japan.
authors.forename: Akiya
authors.initials: A
authors.lastname: Akahoshi
authors.affiliation: Collaborative Research Center for OMIC, Okayama University , Okayama 700-8558 , Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsuura
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation , Kyoto , Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ozeki
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation , Kyoto , Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Medical Bioengineering, Okayama University , Okayama 700-8530 , Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Medical Bioengineering, Okayama University , Okayama 700-8530 , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohtsuki
keywords: 200 Applications; 211 Scaffold/Tissue engineering/Drug delivery; 30 Bio-inspired and biomedical materials; Cell penetrating peptide; drug delivery; lactosome; photosensitizer; polymeric micelle