Innovative photodynamic therapy using rose bengal for the treatment of human melanoma

Rose Bengal (RB), a xanthene dye with established antitumor and immunomodulatory properties, is a cytotoxic molecule evaluated in human melanoma through phase 2 clinical trials. RB demonstrates intrinsic therapeutic activity; however, its clinical application may be limited at high doses because of potential side effects, including photosensitivity. In this context, and given that RB also functions as a photosensitizer (PS), our objective was to enhance its efficacy by introducing a photodynamic therapy (PDT) approach using green light (550 nm) excitation. PDT relies on activation of a PS in the presence of oxygen, generating reactive oxygen species (ROS) that induce tumor cell death and stimulate immune responses. In terms of relative efficacy, PDT-RB was 121 and 40 times more effective than RB alone in HBL and LND melanoma cell lines, respectively. This reduced the RB concentration from 492 μM to 32 μM for HBL and from 1,043 μM to 74 μM for LND, achieving 80% cell death. This combination of light and low RB concentrations enhances ROS production and induces necrosis in metastatic melanoma cells. Moreover, PDT-RB preserves PBMC proliferation compared with high-dose RB, suggesting reduced immunotoxicity and potential immunogenic properties, supporting further investigation in more advanced models for future validation.