A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer

• Published in: Nanomedicine 2013-10, Vol.9 (7), p.1114-1122
• Main Authors: Mir, Youssef, PhD, Elrington, Stefan A., BS, Hasan, Tayyaba, PhD
• Format: Article
• Language: English
• Subjects: Absorption; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Cell Line, Tumor; Cell Survival - drug effects; Cetuximab; Drug delivery; EGFR; Endocytosis - drug effects; ErbB Receptors - metabolism; Female; Flow Cytometry; Fluorescein-5-isothiocyanate - metabolism; Fluorescence; Humans; Immunoblotting; Immunotherapy; Internal Medicine; Liposome; Liposomes - chemistry; Molecular Targeted Therapy; Nanoparticles - chemistry; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Ovarian Neoplasms - therapy; Photochemotherapy; Porphyrins - chemistry; Targeted photodynamic therapy; Verteporfin
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2013.02.005

Abstract Targeted photodynamic therapy (TPDT) involves the administration of a photosensitizer (PS) conjugated with a targeting moiety followed by light activation. The systemic toxicity associated with conventional therapy may thus be significantly reduced in TPDT due to the dual selectivity provided by the spatial localization of the illumination as well as the target-localizing ability of the conjugate. Herein, a photo-immuno-conjugate-associating-liposome (PICAL) for TPDT has been developed in which the FDA approved benzoporphyrin derivative monoacid A (BPD) and the Cetuximab antibody for epidermal growth factor receptor (EGFR) were associated into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. Results have shown that the BPD molecules adsorbed into PICAL have stable optical behavior and a higher fluorescence quantum yield than free-BPD. The Cetuximab adsorbed into PPL selectively binds to cells that overexpress EGFR. The inhibition of EGFR signaling by PICAL has enhanced PDT-mediated ovarian cancer cell death. From the Clinical Editor In this basic science study, a photo-immuno-conjugate-associating-liposome for targeted photodynamic therapy is investigated. The FDA-approved benzoporphyrin derivative monoacid A and an epidermal growth factor receptor antibody were assembed into a stable Preformed Plain Liposome (PPL) by passive physical adsorption. The authors demonstrate therapeutic efficacy of the above construct in an ovarian tumor system.