Studies on BODIPY conjugates of Copper and Zinc for Cellular Imaging and Photodynamic Therapy

Abstract

Cancer is a dreadful disease that occurs due to the uncontrolled division of abnormal cells. Though there are different therapeutic modalities available for cancer, chemotherapy is considered as the most practiced method. It is also well established that the transition metal-based chemotherapeutic agents provide several medicinal benefits in comparison to the purely organic counterparts. However, the efficacy of metal-based anticancer agents, especially the commercial platinum-based drugs is greatly reduced due to the dose-limiting toxicity and associated adverse effects. Shifting to photodynamic therapeutic treatment modality (PDT) may provide better spatio-temporal control on drug action but the clinically approved porphyrinic photosensitizers also show limited success owing to their hydrophobic nature and aggregation-induced photobiological deactivation-related issues under physiological conditions. Though Photofrin®, the FDA approved PDT drug, is found to be useful against a vast group of cancers, it suffers from additional drawbacks like skin photosensitivity and hepatotoxicity. It has been documented that the insertion of selective transition metals inside the porphyrinic core could result significant improvement in their photophysical and photobiological activities but even with the development of metallo-porphyrins, the challenges regarding the hydrophobic and aggregative-nature of these macrocyclic photosensitizers could not be addressed successfully. One possible way is the introduction of non-porphyrinic photosenstizers that should contain only the positive attributes of porphyrin or phthalocyanine-based classical PDT agents. BODIPY or boron-dipyrromethene-based dyes have recently emerged as the preferred alternatives, which are also known as half of porphyrin or porphyrin s little sisters due to their close structural proximity with porphyrin unit. However, despite several promises, quite surprisingly, none of the BODIPY-based molecules have received clinical approval yet for the treatment of PDT.