Targeted Photodynamic Therapy of Human Head and Neck Squamous Cell Carcinoma with Anti-epidermal Growth Factor Receptor Antibody Cetuximab and Photosensitizer IR700DX in the Mouse Skin-fold Window Chamber Model

Autor: Timo L.M. ten Hagen, Kristian Berg, Wei Peng, Max J. H. Witjes, Jan L. N. Roodenburg, Go M. van Dam, Henriette S. de Bruijn, Dominic J. Robinson
Přispěvatelé: Otorhinolaryngology and Head and Neck Surgery, Pathology, ​Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Microbes in Health and Disease (MHD), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Photochemistry and Photobiology
Photochemistry and Photobiology, 96(3), 708-717. Wiley-Blackwell
ISSN: 0031-8655
DOI: 10.1111/php.13267
Popis: Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti‐epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR‐overexpressing human head/neck OSC‐19‐luc2‐cGFP tumor with transfected GFP gene was used in a skin‐fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumor was also irradiated with 690 nm laser light 24 h after conjugate administration. The vascular and tumor responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumor peaked at 24–48 h after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalized in the GFP‐expressing tumor cells. PDT‐treated tumors showed extensive necrotic/apoptotic destruction with little vascular damage, while IHC showed no HIF‐1α expression and decreased EGFR and Ki67 expression with activated caspase‐3 overexpression, indicating a direct killing of tumor cells through both necrotic and apoptotic cell death.
The EGFR overexpressing human head and neck OSC‐19‐luc2‐cGFP tumor with transfected GFP gene was used in a skin‐fold window chamber model in BALB/c nude mice. The tumor localization of the anti‐EGFR cetuximab–IR700DX conjugate was studied by an intravital confocal laser scanning microscopy at 24 h after intravenous injection. The tumor in the window chamber was then irradiated with 690 nm laser light (100 J cm−2 at 50 mW cm−2). The conjugate localizes selectively in tumor cells resulting in necrosis and apoptosis after light exposure.
Databáze: OpenAIRE
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