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.

Synthesis and photodynamic effect of new highly photostable decacationically armed [60]- and [70]fullerene decaiodide monoadducts to target pathogenic bacteria and cancer cells.

Novel water-soluble decacationically armed C(60) and C(70) decaiodide monoadducts, C(60)- and C(70)[>M(C(3)N(6)(+)C(3))(2)], were synthesized, characterized, and applied as photosensitizers and potential nano-PDT agents against pathogenic bacteria and cancer cells. A high number of cationic charges per fullerene cage and H-bonding moieties were designed for rapid binding to the anionic residues displayed on the outer parts of bacterial cell walls. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C(70)[>M(C(3)N(6)(+)C(3))(2)] produced more HO(•) than C(60)[>M(C(3)N(6)(+)C(3))(2)], in addition to (1)O(2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C(60)[>M(C(3)N(6)(+)C(3))(2)] and C(70)[>M(C(3)N(6)(+)C(3))(2)], respectively. The hypothesis is that (1)O(2) can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO(•) to cause real damage.