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/cm². 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.