title: A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Wellman Center for Photomedicine, Department of Dermatology, Bartlett Hall 314, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Mir
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Elrington
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000042:Absorption; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000068818:Cetuximab; D004705:Endocytosis / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D015151:Immunoblotting; D007167:Immunotherapy; D008081:Liposomes / Q000737:chemistry; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry; D000077362:Verteporfin
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D008081:Liposomes; D011166:Porphyrins; D000077362:Verteporfin; D066246:ErbB Receptors; D016650:Fluorescein-5-isothiocyanate; D000068818:Cetuximab
keywords: Drug delivery; EGFR; Liposome; Ovarian cancer; Targeted photodynamic therapy