title: Photochemical enhancement of transgene expression by polymeric micelles incorporating plasmid DNA and dendrimer-based photosensitizer.
abstract: The development of synthetic gene carriers has recently received much attention; however, they might lack the ability to control the transgene expression. The use of external stimuli for enhancement of the transgene expression may be a promising approach for the site-directed transfection in vivo. In this regard, a new technology of "photochemical internalization (PCI)" has recently been reported, in which the endosomal escape of gene carriers is assisted by photodamage of the endosomal membrane with co-incubating photosensitizers. To apply this technology for systemic gene delivery, the development of appropriate carrier systems for both the plasmid DNA (pDNA) and photosensitizer is of crucial importance. Also, the photocytotoxicity accompanied by the photochemical enhancement of the gene expression may need to be reduced. In this study, the combinational formulation of polymeric micelles incorporating pDNA and a dendrimer-based photosensitizer (DP) (dendrimer phthalocyanine (DPc)) was applied in the PCI-mediated transfection in vitro and then, estimating its potential utility for in vivo applications. The PCI using the polymeric micelle system achieved a remarkable photochemical enhancement of the transgene expression while maintaining an approximate 80% cell viability over a wide range of the DPc concentrations and light doses. Thus, this system may be promising for in vivo PCI-mediated gene delivery.
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.lastname: Arnida
authors.forename: Woo-Dong
authors.initials: WD
authors.lastname: Jang
authors.forename: Kotoe
authors.initials: K
authors.lastname: Date
authors.forename: Kanjiro
authors.initials: K
authors.lastname: Miyata
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D016503:Drug Delivery Systems / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles; D008027:Light; D008823:Micelles; D008954:Models, Biological; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D010957:Plasmids / Q000737:chemistry / Q000235:genetics*; D011108:Polymers / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014162:Transfection / Q000379:methods; D019076:Transgenes / Q000235:genetics*
chemical_list: D050091:Dendrimers; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D017319:Photosensitizing Agents; D011108:Polymers; C013647:phthalocyanine