Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine.
Photodynamic therapy (PDT) is a promising method for the localized treatment of solid tumors. In order to enhance the efficacy of PDT, we have recently developed a novel class of photosensitizer formulation, i.e., the dendrimer phthalocyanine (DPc)-encapsulated polymeric micelle (DPc/m). The DPc/m induced efficient and unprecedentedly rapid cell death accompanied by characteristic morphological changes such as blebbing of cell membranes, when the cells were photoirradiated using a low power halogen lamp or a high power diode laser. The fluorescent microscopic observation using organelle-specific dyes demonstrated that DPc/m might accumulate in the endo-/lysosomes; however, upon photoirradiation, DPc/m might be promptly released into the cytoplasm and photodamage the mitochondria, which may account for the enhanced photocytotoxicity of DPc/m. This study also demonstrated that DPc/m showed significantly higher in vivo PDT efficacy than clinically used Photofrin (polyhematoporphyrin esters, PHE) in mice bearing human lung adenocarcinoma A549 cells. Furthermore, the DPc/m-treated mice did not show skin phototoxiciy, which was apparently observed for the PHE-treated mice, under the tested conditions. These results strongly suggest the usefulness of DPc/m in clinical PDT.
Nishiyama
Nobuhiro
N
Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Japan.
Nakagishi
Yoshinori
Y
Morimoto
Yuji
Y
Lai
Ping-Shan
PS
Miyazaki
Kozo
K
Urano
Kyoko
K
Horie
Souta
S
Kumagai
Michiaki
M
Fukushima
Shigeto
S
Cheng
Yu
Y
Jang
Woo-Dong
WD
Kikuchi
Makoto
M
Kataoka
Kazunori
K
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D050091:Dendrimers / Q000737:chemistry*; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D054833:Isoindoles; D007834:Lasers; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D050091:Dendrimers; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; D011107:Polylysine; D011092:Polyethylene Glycols; D017323:Dihematoporphyrin Ether; C013647:phthalocyanine