TY - JOUR
T1 - Stable Synthetic Bacteriochlorins for Photodynamic Therapy
T2 - Role of Dicyano Peripheral Groups, Central Metal Substitution (2H, Zn, Pd), and CremophorEL Delivery
AU - Huang, Ying Ying
AU - Balasubramanian, Thiagarajan
AU - Yang, Eunkyung
AU - Luo, Dianzhong
AU - Diers, James R.
AU - Bocian, David F.
AU - Lindsey, Jonathan S.
AU - Holten, Dewey
AU - Hamblin, Michael R.
PY - 2012/12
Y1 - 2012/12
N2 - A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)2BC and corresponding zinc chelate (NC)2BC-Zn and palladium chelate (NC)2BC-Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N-dimethylacetamide) into serum-containing medium was compared with the dilution of bacteriochlorin in CremophorEL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24h incubation and illumination with 10Jcm-2 of near-infrared (NIR) light is (NC)2BC-Pd (LD50=25nM) > (NC)2BC > (NC)2BC-Zn ≈ BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)2BC-Pd showed PDT-mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers.
AB - A series of four stable synthetic bacteriochlorins was tested in vitro in HeLa cells for their potential in photodynamic therapy (PDT). The parent bacteriochlorin (BC), dicyano derivative (NC)2BC and corresponding zinc chelate (NC)2BC-Zn and palladium chelate (NC)2BC-Pd were studied. Direct dilution of a solution of bacteriochlorin in an organic solvent (N,N-dimethylacetamide) into serum-containing medium was compared with the dilution of bacteriochlorin in CremophorEL (CrEL; polyoxyethylene glycerol triricinoleate) micelles into the same medium. CrEL generally reduced aggregation (as indicated by absorption and fluorescence) and increased activity up to tenfold (depending on bacteriochlorin), although it decreased cellular uptake. The order of PDT activity against HeLa human cancer cells after 24h incubation and illumination with 10Jcm-2 of near-infrared (NIR) light is (NC)2BC-Pd (LD50=25nM) > (NC)2BC > (NC)2BC-Zn ≈ BC. Subcellular localization was determined to be in the endoplasmic reticulum, mitochondria and lysosomes, depending on the bacteriochlorin. (NC)2BC-Pd showed PDT-mediated damage to mitochondria and lysosomes, and the greatest production of hydroxyl radicals as determined using a hydroxyphenylfluorescein probe. The incorporation of cyano substituents provides an excellent motif for the enhancement of the photoactivity and photostability of bacteriochlorins as PDT photosensitizers.
KW - Antitumor agents
KW - CremophorEL micelles
KW - Photodynamic therapy
KW - Photostability
KW - Reactive oxygen species
KW - Synthetic bacteriochlorins
UR - https://www.scopus.com/pages/publications/84870273686
U2 - 10.1002/cmdc.201200351
DO - 10.1002/cmdc.201200351
M3 - Article
C2 - 23065820
AN - SCOPUS:84870273686
SN - 1860-7179
VL - 7
SP - 2155
EP - 2167
JO - ChemMedChem
JF - ChemMedChem
IS - 12
ER -