Induction of intensive tumor suppression by antiangiogenic photodynamic therapy using polycation-modified liposomal photosensitizer

Authors

  • Yoshito Takeuchi M.Eng.,

    1. Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan
    2. Japan Society for the Promotion of Science, Tokyo, Japan
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  • Kohta Kurohane Ph.D.,

    1. Department of Microbiology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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  • Kanae Ichikawa B.Pharm.,

    1. Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan
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  • Sei Yonezawa B.Pharm.,

    1. Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan
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  • Mamoru Nango Ph.D.,

    1. Department of Applied Chemistry, Faculty of Engineering, Nagoya Institute of Technology, Nagoya, Japan
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  • Naoto Oku Ph.D.

    Corresponding author
    1. Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan
    • Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
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    • Fax: (011) 81 54 264 5705


Abstract

BACKGROUND

The authors previously observed that antiangiogenic scheduling of photodynamic therapy (PDT) was effective in causing tumor regression through hemostasis. It would thus be expected that photosensitizer entrapped in polycation liposomes (PCLs) would be efficiently taken up in tumor-derived angiogenic vascular endothelial cells due to the strong electrostatic adhesion between the polycation and the plasma membrane, thus resulting in enhanced phototherapeutic efficacy.

METHODS

Tumors and angiogenesis were induced by subcutaneous injection of Meth-A sarcoma cells into 5-week-old male BALB/c mice. PDT treatment was performed by an intravenous (i.v.) injection of benzoporphyrin derivative monoacid ring A (BPD-MA)-entrapped liposomes or the PCLs (0.25 mg/kg in terms of BPD-MA), followed by exposure to a laser light of 689 nm with 150 J/cm2 of fluence 15 minutes post injection.

RESULTS

As a result of PDT on angiogenesis-model mice prepared by the dorsal air sac technique, neovascular destruction after laser irradiation was observed when BPD-MA entrapped in PCLs was used. Furthermore, strong suppression of tumor growth was identified by the PCL-mediated PDT treatment along with a prolonged life span for the mice. Destruction of angiogenic vessels and subsequent tumor cell apoptosis were observed after PCL-mediated PDT treatment in an immunofluorescence study. Interestingly, the biodistribution of the injected BPD-MA that was delivered by PCLs indicated invariable photosensitization levels in tumor tissues.

CONCLUSIONS

The study revealed that antiangiogenic PDT treatment using a low dose of BPD-MA entrapped in PCLs efficiently induced the destruction of angiogenic vessels and subsequent tumor suppression by vessel occlusion. Cancer 2003;97:2027–34. © 2003 American Cancer Society.

DOI 10.1002/cncr.11283

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