In vitro photodynamic effects of phthalocyaninatosilicon covalently linked to 2,2,6,6-tetramethyl-1-piperidinyloxy radicals on cancer cells.

In this paper, we have investigated the ability to sensitize the phototoxicity toward HeLa cells in vitro, of tetra-tert-butylphthalocyaninatosilicon (SiPc) covalently linked to one or two 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals (R1c or R2c), which are shown as photosensitizers efficiently producing singlet oxygen (1Delta(g)). Addition of R1c or R2c encapsulated in liposomes to cultures, followed by irradiation with a 680-nm dye laser, resulted in a highly significant phototoxicity toward HeLa cells, in contrast to negligible phototoxicity observed with (dihydroxy)SiPc (R0). EPR measurements indicate that R1c and R2c exist in some degree as nitroxide radicals even in HeLa cells. Electronic absorption spectra indicate that the degree of aggregation increases in the order R2c<R1c<R0. Thus, the high phototoxicity of R1c and R2c toward HeLa cells is reasonably interpreted by both the large singlet oxygen yield and the inhibition of aggregation due to the bulky TEMPO radicals. This increase in photodynamic effect on HeLa cells is an unusual and important example for increasing the photobiological reaction yields using paramagnetic radicals.