Photodynamic Therapy with Water-Soluble Cationic Fullerene Derivatives

Abstract

Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers (PS) and visible light that, after light absorption, can produce long-lived excited triplet states of the chromophore, that are able to carry out a sequence of photochemical reactions in the presence of oxygen to produce reactive oxygen species (ROS). These photoinduced ROS are capable of nonspecific killing of undesirable species that include cancer cells, pathogenic bacteria, fungi, and viruses. Functionalized fullerene derivatives with the preservation of an extended π-conjugation on the surface of carbon cage structure are prone to undergo photoexcitation by UV/visible light that leads to the formation of long-lived triplet states in a high quantum yield. This can facilitate photochemistry that results in the production of either reactive free radicals (Type I) or singlet oxygen (Type II) that both cause biological damage. Despite the demonstrated ability of these fullerenes to scavenge ROS as a concurrent competitive event with their production, illuminated fullerenes were found to be highly efficient in mediating PDT. Many reports have shown light-dependent in vitro killing of various cell types after incubation with functionalized fullerenes that have been chemically modified and derivatized (frequently with cationic charges) or encapsulated in drug delivery vehicles to enhance water solubility. In vivo reports of PDT with fullerenes include their use to destroy or inhibit tumors growing in mice and to increase survival in a challenging disseminated abdominal cancer model. An illuminated cationic fullerene was demonstrated to save the life of mice with wounds infected with pathogenic gram-negative bacteria. We and others have also used cationic fullerene PDT to treat mouse models of various cancers including a disseminated model of metastatic cancer in the peritoneal cavity. Multifunctional water-soluble fullerenes may have the potential to join the range of PSs that are clinically approved for use in the PDT field in the future. Accordingly, in vivo PDT with highly charged fullerene derivatives may represent a new application for disease treatment in the field of nanomedicine.