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.

The Noninvasive Treatment for Sentinel Lymph Node Metastasis by Photodynamic Therapy Using Phospholipid Polymer as a Nanotransporter of Verteporfin

“…The treatable size of metastasis by PDT is still to be elucidated. Our previous study using murine model showed that PDT decreased the tumor size from almost 2,000 mm 3 to 150 mm 3 [11]. Moreover, phase 2 study of PDT against skin cancers revealed that the rate of histopathologic response, defined by absence of tumor on biopsy specimen, was 73% in tumor 1-2 cm in size [25].…”

“…In the presence of oxygen, the activated photosensitizer can generate reactive oxygen species that cause cell damage and ultimately cell death [11]. Verteporfin is a hydrophobic polyporphyrin oligomer with two structural isomers, a short photosensitivity period [12], and maximum absorption at 689 nm.…”

Photodynamic Therapy–Induced Angiogenic Signaling: Consequences and Solutions to Improve Therapeutic Response

“…However, this study did not evaluate the effect of TPC-heptapeptide PDT on tumor cell kill in vivo. Kameyama, et al [51] constructed a synthetic nanoparticle that contained Verteporfin and was conjugated to an anti-EGFR antibody to achieve tumor cell specificity. When mice bearing A431 tumors received this nanoparticle and light, the authors noted prolonged survival compared to controls.…”

Can nanotechnology potentiate photodynamic therapy?

“…Stuchinskaya et al [263] recently published an antibody-phthalocyanine-AuNP conjugate to selectively target breast cancer cells that overexpress the HER2 EGF receptor (EGFR). Kameyama et al [264] used the conjugation of an anti-EGFR MoAb with a verteporfi n-loaded nanoparticles. They found a threefold higher incorporation of the complex into A431 cells in vitro , and the tumor size in vivo experiments showed a signifi cant decrease compared with tumors treated with verteporfi n-nanoparticle complex without the antibody.…”