Targeted Photodynamic Therapy and Photochemical Internalization of Human Head and Neck Cancer: a preclinical study in vitro and in vivo

Abstract

Photodynamic therapy (PDT) is a treatment modality based on a tumour-localising photosensitizer and light exposure to induce necrosis and apoptosis of tumour cells. It is used to treat head and neck cancer, but its inadequate selectivity and specificity lead to phototoxicity of normal tissues. Targeted PDT employs a conjugate, a dye and an antibody (against a tumour-overexpressing molecule), to enhance selectivity and specificity of PDT. Photochemical internalisation (PCI) uses the principle of PDT for light-enhanced cytosolic release of anti-cancer drugs that are entrapped in the endo/lysosomal vesicles of cancer cells. The aims of this thesis were to improve selectivity and specificity of PDT and PCI with cetuximab-IR700DX conjugate. The thesis started with studying killing effects of targeted PDT in human head and neck tumour cell lines. Such therapeutic effects were then confirmed in a xenografted human head and neck tumour in a mouse skin-fold window-chamber model in vivo. A low light fluence rate enhanced such targeted PDT effects. The thesis was ended with investigating bleomycin-based PCI with temoporfin and gelonin-based PCI with targeted PDT in the human tumour cell lines in vitro.