title: Disulfide crosslinked polyion complex micelles encapsulating dendrimer phthalocyanine directed to improved efficiency of photodynamic therapy.
abstract: Dendrimer phthalocyanine (DPc)-loaded polyion complex micelle (DPc/m) has been developed as photosensitizer (PS) formulation in photodynamic therapy (PDT). Incorporation of DPc into the micelle showed significant enhancement in the in vitro photocytotoxicity. Also, introduction of disulfide crosslinking in the micellar core further improved the in vitro PDT effect of DPc/m. Here, we aim to analyze the mechanism of the enhanced photocytotoxicity of DPc/m, particularly focusing on the photochemical reactions during photoirradiation. As a result, DPc/m has been shown to protect DPc from photobleaching induced by the reactions with serum proteins, although DPc were considerably quenched in the micellar core. Furthermore, the introduction of disulfide crosslinking into the micellar core has demonstrated to improve the efficiency of reactive oxygen species (ROS) production by DPc in the micellar core as well as more effectively prevent the photobleaching of DPc. These effects might lead to effective photochemical reactions by DPc/m, which may account for the enhanced photocytotoxicity. Our findings provide useful knowledge in designing PS formulations for effective PDT.
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Japan.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Herlambang
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kumagai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nomoto
authors.forename: Souta
authors.initials: S
authors.lastname: Horie
authors.forename: Shigeto
authors.initials: S
authors.lastname: Fukushima
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.forename: Kozo
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003432:Cross-Linking Reagents / Q000737:chemistry*; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004220:Disulfides / Q000737:chemistry*; D004339:Drug Compounding; D004705:Endocytosis; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles; D008027:Light; D008823:Micelles; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015394:Molecular Structure; D038761:Photobleaching; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D013499:Surface Properties
chemical_list: D003432:Cross-Linking Reagents; D050091:Dendrimers; D004220:Disulfides; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C013647:phthalocyanine