TY - JOUR
T1 - In vitro photodynamic effects of phthalocyaninatosilicon covalently linked to 2,2,6,6-tetramethyl-1-piperidinyloxy radicals on cancer cells
AU - Ishii, Kazuyuki
AU - Takayanagi, Atsushi
AU - Shimizu, Shinsuke
AU - Abe, Hisaku
AU - Sogawa, Kazuhiro
AU - Kobayashi, Nagao
N1 - Funding Information:
We thank Dr. Ken-ichi Yasumoto for his help with the DNA fragmentation assay. This work was supported by a Grant-in-Aid for Young Scientists (Category A No. 14703007), Scientific Research in Priority Areas “Diagnosis and Treatment of Cancer” (No. 15025212 and 16023213), and the COE project, Giant Molecules and Complex Systems, 2004 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - 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 ( 1Δg). 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.
AB - 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 ( 1Δg). 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.
KW - Free radicals
KW - Nitroxide radical
KW - Photodynamic therapy
KW - Phthalocyanine
KW - Porphyrin
KW - Singlet oxygen
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U2 - 10.1016/j.freeradbiomed.2004.12.017
DO - 10.1016/j.freeradbiomed.2004.12.017
M3 - Article
C2 - 15749388
AN - SCOPUS:14644402453
VL - 38
SP - 920
EP - 927
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 7
ER -