Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine

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

Research output: Contribution to journalArticle

122 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)245-251
Number of pages7
JournalJournal of Controlled Release
Volume133
Issue number3
DOIs
Publication statusPublished - 2009 Feb 10

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Nishiyama, N., Nakagishi, Y., Morimoto, Y., Lai, P. S., Miyazaki, K., Urano, K., Horie, S., Kumagai, M., Fukushima, S., Cheng, Y., Jang, W. D., Kikuchi, M., & Kataoka, K. (2009). Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine. Journal of Controlled Release, 133(3), 245-251. https://doi.org/10.1016/j.jconrel.2008.10.010