Photodynamic therapy (PDT) is a minimally invasive therapeutic approach for the treatment of various conditions including cancers. A key feature of PDT is the light-absorbing photosensitiser, which is activated in the presence of oxygen and a specific wavelength of light, leading to the generation of reactive oxygen species (ROS) and cell death. ‘First generation’ photosensitisers have been commercialised to treat numerous malignancies including lung and skin cancers. However, disadvantages such as low purity, poor stability, photosensitivity, and poor absorbance have prompted the development of novel photosensitisers to improve PDT outcomes.
We have identified a new chlorin-based photosensitiser – Phyllochlorin Sodium. Phyllochlorin sodium with improved characteristics of chlorin-based photosensitisers.
Our study has demonstrated that phyllochlorin sodium can generate a high yield of ROS in the form of singlet oxygen, with rapid cellular uptake and localisation to subcellular regions in the endoplasmic reticulum. When compared to similar photosensitisers such as chlorin e4 disodium salt, chlorin e6 trisodium salt (Photolon), chlorin e6 dimeglumine salt (Photodithiazine) and chlorin e6 trimeglumine salt (KIA), phyllochlorin sodium had significantly greater phototoxicity upon light activation, with low toxicity in the absence of light. In tumour-bearing mice, phyllochlorin sodium was found to accumulate and remain in tumours when compared to normal cells.
We present here our next generation phyllochlorin sodium photosensitiser and demonstrate its increased stability and enhanced phototoxicity in cancer cells compared to similar compounds. Our study offers new insight into the development of a novel family of photosensitisers and their potential clinical efficacy and application for PDT.