Photoinduced electron-transfer mechanisms for radical-enhanced photodynamic therapy mediated by water-soluble decacationic C70 and C84O2 Fullerene Derivatives

Abstract

Fullerenes are promising candidates for photodynamic therapy (PDT). Thus, C70 and novel C84O2 fullerenes were functionalized with and without an additional deca-tertiary ethyleneamino-chain as an electron source, giving rise to two distinct pairs of photosensitizers, the monoadducts LC-17, LC-19 and the bisadducts LC18 and LC-20 to perform PDT in HeLa cells with UVA, blue, green, white and red light. Shorter wavelengths gave more phototoxicity with LC-20 while LC-19 was better at longer wavelengths; the ratio between killing obtained with LC-19 and LC-20 showed an almost perfect linear correlation (R = 0.975) with wavelength. The incorporation of a deca-tertiary amine chain in the C84O2 fullerene gave more PDT killing when excited with shorter wavelengths or in the presence of low ascorbate concentration through higher generation of hydroxyl radicals. Photoactivated C84O2 fullerenes induced apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage demonstrated by acridine orange and rhodamine 123 fluorescent probes. From the Clinical EditorPhotoactivated C70 and C84O2 fullerenes were demonstrated to induce apoptosis of HeLa cancer cells, together with mitochondrial and lysosomal damage, as a function of wavelength. The study is paving the way to future clinical uses of these agents in photodynamic therapy.