Photodynamic Therapy of Head and Neck Cancers with Ruthenium-based Photosensitizers

Abstract

SignificanceThe management of patients with head and neck cancers relies mainly on platinum-based chemotherapies. However, severe side effects and tumor resistance impair treatment efficacy, notably due to frequent mutations of the TP53 tumor suppressor. Here we propose a ruthenium-based photodynamic therapy as a p53-independent therapeutic strategy, and show that its phototoxicity relies on the induction of endoplasmic reticulum stress and immunogenic cell death. ApproachSQ20B cells were treated with the Ru I ruthenium-based photosensitizer prior to illumination. Ru I cytotoxicity and mode of action were studied using molecular and cellular read-outs. ResultsRu I showed an interesting phototoxicity and triggered the expression of key markers of endoplasmic reticulum stress and early stages of immunogenic cell death. ConclusionsRu I-PDT appears to be efficient in vitro on head and neck cancer models. Its phototoxicity seems to be associated to two p53-independent pathways, whose functional links remain to be clarified.