Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine.

Abstract

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.

• Authors: Nobuhiro Nishiyama, Yoshinori Nakagishi, Yuji Morimoto, Ping-Shan Lai, Kozo Miyazaki, Kyoko Urano, Souta Horie, Michiaki Kumagai, Shigeto Fukushima, Yu Cheng, Woo-Dong Jang, Makoto Kikuchi, Kazunori Kataoka
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 133 Issue 3 Pg. 245-51 (Feb 10 2009) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 19000725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dendrimers
• Indoles
• Isoindoles
• Micelles
• Radiation-Sensitizing Agents
• Reactive Oxygen Species
• Polylysine
• Polyethylene Glycols
• Dihematoporphyrin Ether
• phthalocyanine

Topics

• Animals
• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• Dendrimers (chemistry)
• Dihematoporphyrin Ether (administration & dosage, chemistry, therapeutic use)
• Drug Delivery Systems (methods)
• Female
• Humans
• Indoles (administration & dosage, chemistry, therapeutic use)
• Isoindoles
• Lasers
• Liver (drug effects, pathology)
• Mice
• Mice, Inbred BALB C
• Micelles
• Nanoparticles
• Neoplasms (drug therapy, metabolism, pathology)
• Photochemotherapy (adverse effects, methods)
• Polyethylene Glycols (chemistry)
• Polylysine (chemistry)
• Radiation-Sensitizing Agents (administration & dosage, chemistry, therapeutic use)
• Reactive Oxygen Species (metabolism)
• Skin (drug effects, pathology)
• Xenograft Model Antitumor Assays