Two-photon PDT as a new and minimally-invasive approach for treatment of melanoma cancer: synthesis of photosensitizers

Melanoma is an aggressive cancer with a high rate of mortality and morbidity due to its unresponsiveness to conventional radiotherapy and chemotherapy. Photodynamic Therapy (PDT) is a minimally-invasive technique that combines a photosensitiser, light and oxygen to induce cell death. Although an established modality for non-melanoma skin cancers, it is currently not suitable for melanoma since the (visible) activating light has very limited penetration due to the high tumour pigmentation. This limitation can be overcome by using an innovative strategy based on two-photon excitation photodynamic therapy (TPE-PDT) for the destruction of melanoma.[1] It requires the design of specific two-photon absorbing photosensitisers that bypass the absorption of the high melanin content of melanomas and the use of excitation in the near-infrared (NIR) for a deep penetration of light, to perform an efficient treatment. Porphyrin derivatives were developed in the group as TP photosensitisers to perform PDT in the NIR.[2] They have very appealing features for TP-PDT, a large TP absorption cross-section (s2 > 1000 GM) in the NIR and significant singlet oxygen production (0.5-0.6 in DMSO). TP excitation at 910 nm performed on cancer cells incubated with such molecules led to important cell death.[3] Based on these results, a new family of PSs with a large ?-delocalized system and using folic acid as a vector was designed within sight of treating melanoma cancer.