Ru(II)‐Cyanine Complexes as Promising Photodynamic Photosensitizers for the Treatment of Hypoxic Tumours with Highly Penetrating 770 nm Near‐Infrared Light
Résumé
Light‐activated treatments, such as photodynamic therapy (PDT), provide temporal and spatial control over a specific cytotoxic response by exploiting toxicity differences between irradiated and dark conditions. In this work, a novel strategy for developing near infrared (NIR)‐activatable Ru(II) polypyridyl‐based photosensitizers (PSs) was successfully developed through the incorporation of symmetric heptamethine cyanine dyes in the metal complex via a phenanthrimidazole ligand. Owing to their strong absorption in the NIR region, the PSs could be efficiently photoactivated with highly penetrating NIR light (770 nm), leading to high photocytotoxicities towards several cancer cell lines under both normoxic and hypoxic conditions. Notably, our lead PS (Ru‐Cyn‐1), which accumulated in the mitochondria, exhibited a good photocytotoxic activity under challenging low‐oxygen concentration (2% O2) upon NIR light irradiation conditions (770 nm), owing to a combination of types I and II PDT mechanism. The fact that the PS Protoporphyrin IX (PpIX), the metabolite of the clinically approved 5‐ALA PS, was found inactive under the same challenging conditions positions Ru‐Cyn‐1 complex as a promising PDT agent for the treatment of deep‐seated hypoxic tumours.
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