title: 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.affiliation: Department of Surgery, International Goodwill Hospital, Yokohama, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kameyama
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Itano
authors.forename: Arisa
authors.initials: A
authors.lastname: Ito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Konno
authors.forename: Tsunenori
authors.initials: T
authors.lastname: Arai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishihara
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ueda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011112:Polymyxin B / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D015996:Survival Rate; D000077362:Verteporfin
chemical_list: D000911:Antibodies, Monoclonal; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C038934:polymyxin B nonapeptide; D066246:ErbB Receptors; D011112:Polymyxin B