Photodynamic therapy using an anti-EGF receptor antibody complexed with verteporfin nanoparticles: a proof of concept study.

Abstract

Photodynamic therapy (PDT) is a noninvasive optical treatment method in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with broadband red light. Coupling photosensitizers with a specific antibody may allow this approach to target specific cancers. This study determines the antitumor efficacy of coupling verteporfin (Visudyne(®)), a hydrophobic polyporphryin oligomer, with an antiepidermal growth factor receptor (anti-EGFR) antibody. Poly[2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-nitrophenylcarbonyloxyethyl methacrylate] (PMBN) was conjugated with an anti-EGFR antibody and mixed with verteporfin (verteporfin-PMBN-antibody complex). Tumor-bearing mice were intravenously injected with the verteporfin-PMBN-antibody complex or verteporfin plus PMBN without the antibody. Irradiation was conducted at 640 nm with a dose of 75 J/cm(2). The fluorescence intensity in A431 cells in vitro was threefold higher after exposure to verteporfin-PMBN-antibody complex than after exposure to verteporfin-PMBN. In A431 tumor-bearing mice, the intratumor concentration of verteporfin was 9.4 times higher than that of the skin, following administration of the verteporfin-PMBN-antibody complex. Tumor size significantly decreased within 8 days in mice treated with verteporfin-PMBN-antibody complex compared with those treated with verteporfin-PMBN. PDT using a PMBN-verteporfin-antibody complex offers a promising anticancer therapy.

• Authors: Noriaki Kameyama, Sachiko Matsuda, Osamu Itano, Arisa Ito, Tomohiro Konno, Tsunenori Arai, Kazuhiko Ishihara, Masakazu Ueda, Yuko Kitagawa
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 26 Issue 6 Pg. 697-704 (Dec 2011) ISSN: 1557-8852 [Electronic] United States
• PMID: 21861705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Photosensitizing Agents
• Porphyrins
• Verteporfin
• polymyxin B nonapeptide
• ErbB Receptors
• Polymyxin B

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Carcinoma, Squamous Cell (drug therapy)
• Cell Line, Tumor
• ErbB Receptors (antagonists & inhibitors)
• Female
• Lung Neoplasms (drug therapy)
• Mice
• Mice, Inbred BALB C
• Nanoparticles (administration & dosage)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacology)
• Polymyxin B (analogs & derivatives, chemistry, pharmacology)
• Porphyrins (pharmacology)
• Survival Rate
• Verteporfin