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

121 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

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Dendrimers
Photochemotherapy
Neoplasms
Therapeutics
Esters
Dihematoporphyrin Ether
Semiconductor Lasers
Halogens
Photosensitizing Agents
phthalocyanine
Micelles
Blister
Lysosomes
Organelles
Mitochondria
Cytoplasm
Cell Death
Coloring Agents
Cell Membrane
Skin

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Nishiyama, N., Nakagishi, Y., Morimoto, Y., Lai, P. S., Miyazaki, K., Urano, K., ... 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
Nishiyama, Nobuhiro ; Nakagishi, Yoshinori ; Morimoto, Yuji ; Lai, Ping Shan ; Miyazaki, Kozo ; Urano, Kyoko ; Horie, Souta ; Kumagai, Michiaki ; Fukushima, Shigeto ; Cheng, Yu ; Jang, Woo Dong ; Kikuchi, Makoto ; Kataoka, Kazunori. / Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine. In: Journal of Controlled Release. 2009 ; Vol. 133, No. 3. pp. 245-251.
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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{\circledR} (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.",
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Nishiyama, N, Nakagishi, Y, Morimoto, Y, Lai, PS, Miyazaki, K, Urano, K, Horie, S, Kumagai, M, Fukushima, S, Cheng, Y, Jang, WD, Kikuchi, M & Kataoka, K 2009, 'Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine', Journal of Controlled Release, vol. 133, no. 3, pp. 245-251. https://doi.org/10.1016/j.jconrel.2008.10.010

Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine. / Nishiyama, Nobuhiro; Nakagishi, Yoshinori; Morimoto, Yuji; Lai, Ping Shan; Miyazaki, Kozo; Urano, Kyoko; Horie, Souta; Kumagai, Michiaki; Fukushima, Shigeto; Cheng, Yu; Jang, Woo Dong; Kikuchi, Makoto; Kataoka, Kazunori.

In: Journal of Controlled Release, Vol. 133, No. 3, 10.02.2009, p. 245-251.

Research output: Contribution to journalArticle

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T1 - Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine

AU - Nishiyama, Nobuhiro

AU - Nakagishi, Yoshinori

AU - Morimoto, Yuji

AU - Lai, Ping Shan

AU - Miyazaki, Kozo

AU - Urano, Kyoko

AU - Horie, Souta

AU - Kumagai, Michiaki

AU - Fukushima, Shigeto

AU - Cheng, Yu

AU - Jang, Woo Dong

AU - Kikuchi, Makoto

AU - Kataoka, Kazunori

PY - 2009/2/10

Y1 - 2009/2/10

N2 - 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.

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