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

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 Editor: Photoactivated 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.