A sulfur-substituted hemicyanine for cancer photothermal therapy without influence of intracellular viscosity

Although photothermal therapy (PTT) has emerged as an appealing strategy for cancer treatment, the development of photothermal agents capable of precisely controlling temperature remains a challenge. In this paper, we present a novel synthetic photosensitizer based on a sulfur-substituted hemicyanine. It was discovered that replacing an oxygen atom in a hemicyanine derivative with a sulfur atom significantly enhances photothermal efficiency and enables lysosome targeting in cancer cells. More importantly, because of the rigid planer structure of the sulfur-substituted hemicyanine, which differs from traditional photothermal agents (PTAs) based on twisted intramolecular charge transfer (TICT) or group rotation mechanisms, the efficiency of photothermal conversion is not affected by intracellular viscosity, allowing precise temperature control during PTT. Further modifying the agent with a glutathione-responsive moiety allows the PTAs to be activated only in cancer cells. The newly proposed PTA achieves efficient PTT in a tumor-bearing mouse model while having negligible toxic side effects on healthy tissues.