TY - JOUR
T1 - Cycloimide bacteriochlorin p derivatives: Photodynamic properties and cellular and tissue distribution
AU - Sharonov, George V.
AU - Karmakova, Tatyana A.
AU - Kassies, R.
AU - Pljutinskaya, Anna D.
AU - Otto, Cornelis
PY - 2006
Y1 - 2006
N2 - Reactive oxygen species generated by photosensitizers are efficacious remedy for tumor eradication. Eleven cycloimide derivatives of bacteriochlorin p (CIBCs) with different N-substituents at the fused imide ring and various substituents replacing the 3-acetyl group were evaluated as photosensitizers with special emphasis on structure–activity relationships. The studied CIBCs absorb light within a tissue transparency window (780–830 nm) and possess high photostability at prolonged light irradiation. The most active derivatives are 300-fold more phototoxic toward HeLa and A549 cells than the clinically used photosensitizer Photogem due to the substituents that improve intracellular accumulation (distribution ratio of 8–13) and provide efficient photoinduced singlet oxygen generation (quantum yields of 0.54–0.57). The substituents predefine selective CIBC targeting to lipid droplets, Golgi apparatus, and lysosomes or provide mixed lipid droplets and Golgi apparatus localization in cancer cells. Lipid droplets and Golgi apparatus are critically sensitive to photoinduced damage. The average lethal dose of CIBC-generated singlet oxygen per volume unit of cell was estimated to be 0.22 mM. Confocal fluorescence analysis of tissue sections of tumor-bearing mice revealed the features of tissue distribution of selected CIBCs and, in particular, their ability to accumulate in tumor nodules and surrounding connective tissues. Considering the short-range action of singlet oxygen, these properties of CIBCs are prerequisite to efficient antitumor photodynamic therapy.
AB - Reactive oxygen species generated by photosensitizers are efficacious remedy for tumor eradication. Eleven cycloimide derivatives of bacteriochlorin p (CIBCs) with different N-substituents at the fused imide ring and various substituents replacing the 3-acetyl group were evaluated as photosensitizers with special emphasis on structure–activity relationships. The studied CIBCs absorb light within a tissue transparency window (780–830 nm) and possess high photostability at prolonged light irradiation. The most active derivatives are 300-fold more phototoxic toward HeLa and A549 cells than the clinically used photosensitizer Photogem due to the substituents that improve intracellular accumulation (distribution ratio of 8–13) and provide efficient photoinduced singlet oxygen generation (quantum yields of 0.54–0.57). The substituents predefine selective CIBC targeting to lipid droplets, Golgi apparatus, and lysosomes or provide mixed lipid droplets and Golgi apparatus localization in cancer cells. Lipid droplets and Golgi apparatus are critically sensitive to photoinduced damage. The average lethal dose of CIBC-generated singlet oxygen per volume unit of cell was estimated to be 0.22 mM. Confocal fluorescence analysis of tissue sections of tumor-bearing mice revealed the features of tissue distribution of selected CIBCs and, in particular, their ability to accumulate in tumor nodules and surrounding connective tissues. Considering the short-range action of singlet oxygen, these properties of CIBCs are prerequisite to efficient antitumor photodynamic therapy.
KW - Free radicals
KW - Cycloimide bacteriochlorin p
KW - Confocal
KW - IR-78505
KW - Near-IR photosensitizer
KW - Photodynamic
KW - Singlet oxygen
U2 - 10.1016/j.freeradbiomed.2005.08.028
DO - 10.1016/j.freeradbiomed.2005.08.028
M3 - Article
SN - 0891-5849
VL - 40
SP - 407
EP - 419
JO - Free radical biology and medicine
JF - Free radical biology and medicine
IS - 3
ER -