Testing ruthenium-based photoactivated chemotherapy on tumor-bearing mice models as a new treatment for uveal melanoma

Currently, there is no approved standard treatment for metastatic uveal melanoma and those approved for primary eye tumors are quite harmful to patients whose vision is often deteriorated or even lost[1]. New clinical options are more than necessary. Because eyes are transparent to light and lasers are widely used in ophthalmology, photoactivated therapies represent an appealing modality for treating eye cancer. Light-activated technologies can be also used for liver metastasis through laparoscopy. Photoactivated chemotherapy (PACT) is a new light-activated technology combining the low systemic toxicity observed for photodynamic therapy (PDT), and the possibility of being activated in oxygen-poor tumors[2,3]. Here we investigated pre-clinically the relevance of ruthenium-based PACT compounds for anticancer therapies in the context of uveal melanoma. In vitro experiments were conducted to determine the photocytotoxicity, the mode of cell death of these compounds and compare them to that of clinically used PDT compounds, both in normoxia and hypoxia environments. In vivo, biodistribution and anticancer efficacy studies were conducted using subcutaneous tumor models in mice, to investigate the best treatment scheme, e.g., drug-to-light interval, treatment dose, and light dose. Biosafety studies were also conducted through blood tests of drug-induced liver injury and acute kidney injury specific markers. Altogether our results show promising apoptotic photocytotoxicity and a high antitumor efficacy, combined with rapid blood clearance and good biosafety in vivo. These results in subcutaneous tumor models are promising and highlight the need for testing this new technology in clinically more relevant orthotopic tumor models in mice.