Synthesis of thiol-appended gold and rhenium corroles as potential nanoconjugants for gold nanoparticles

Abstract

Photodynamic therapy (PDT) today is an established treatment for a variety of cancers as well as various dermatological conditions, macular degeneration and bacterial and other infections. Treatment involves the administration of a photosensitizer, typically a porphyrin, followed by irradiation with light. The photoexcited sensitizer transfers its excess energy to oxygen in the affected tissue, thereby exciting the latter to its highly reactive singlet state. The singlet oxygen serves as the key agent that destroys the diseased tissue. For PDT to work, a photosensitizer has to effectively localize in diseased tissue. It has long been empirically known that porphyrin-type compounds selectively localize in tumors. There is much room for improvement, however, in the area of biodelivery to the tissue in question. Nanoconjugation, i.e., conjugation with nanomaterials such as gold nanoparticles can dramatically enhance drug biodelivery for a variety of target tissues. In this thesis, I have synthesized thiol-appended 5d metallocorroles that are potentially suitable for nanoconjugation with gold nanoparticles.

Gold and rhenium-oxo corroles synthesized in our laboratory are a new class of triplet photosensitizers that have exhibited promise in in vitro photocytotoxicity studies against multiple cancer cell lines. Out of a variety of strategies attempted for appending sulfur-containing substituent, the most promising has been one involving nucleophilic substitution of meso-pentafluorophenyl groups with dithiols. Future work will focus on the synthesis of gold nanoconjugates and testing of the conjugates for phodynamic, photothermal, and radiosensitizing activity. Multimodal activity will be an exciting and gratifying outcome for this line of research.