Skin cancer is the most common cancer in the U.S.A. and Europe. Its subtype, squamous skin carcinoma (SCC), if allowed to grow, has the potential to metastasize and can become deadly. Currently, carbon nanomaterials are being developed to treat cancer due to their attractive physicochemical and biological properties such as an enhanced permeability effect and their ability to produce reactive oxygen species. Here, we describe the synthesis of two water-soluble aminofullerenes (MonoaminoC60 and HexakisaminoC60), which were evaluated as novel [60]fullerene based photosentizers exhibiting anticancer properties. Moreover, the previously described neutral glycofullerene GF1 and its peracetylated lipophilic precursor MMS48 were compared with the aminofullerenes for their ability to generate reactive oxygen species and oxidize lipids. Remarkably, the generation of singlet oxygen and a superoxide radical by HexakisaminoC60 was found to be markedly elevated in the presence of bovine serum albumin and NADH, respectively. Mechanistic studies of lipid peroxidation using cholesterol as a unique reporter molecule revealed that although all four fullerene nanomaterials primarily generated singlet oxygen, superoxide anion was also formed, which suggest a mixed mechanism of action (in which Type I and Type II photochemistry is involved). The [60]fullerene derivative HexakisaminoC60 was also studied for its phototoxicity in squamous skin cancer cell line (A431) using the MTT test and propidium iodide staining.
Keywords: EPR spin trapping; [60]fullerene; lipid peroxidation; non-melanoma skin cancer; photodynamic therapy; singlet oxygen.