Stable synthetic bacteriochlorins for photodynamic therapy: role of dicyano peripheral groups, central metal substitution (2H, Zn, Pd), and Cremophor EL delivery.
Stable synthetic bacteriochlorins for photodynamic therapy: role of dicyano peripheral groups, central metal substitution (2H, Zn, Pd), and Cremophor EL delivery.
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稳定的用于光动力疗法的合成细菌蛋白：二氯外周组，中央金属取代（2H，Zn，PD）和Cremophor EL递送的作用。
DOI：
10.1002/cmdc.201200351
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发表时间：
2012-12
期刊：
影响因子：
3.4
通讯作者：
Hamblin, Michael R.
中科院分区：
文献类型：
--
作者：
Huang, Ying-Ying;Balasubramanian, Thiagarajan;Yang, Eunkyung;Luo, Dianzhong;Diers, James R.;Bocian, David F.;Lindsey, Jonathan S.;Holten, Dewey;Hamblin, Michael R.
关键词：
在体外HeLa细胞中对4种稳定的合成细菌氯进行了光动力治疗（PDT）的潜力测试。研究了母体细菌氯（BC）、二氰衍生物（NC）2BC及其相应的锌螯合物（NC）2BC - zn和钯螯合物（NC）2BC - pd。用有机溶剂（N，N-二甲基乙酰胺）将菌氯溶液直接稀释到含血清的培养基中，与用Cremophor EL （CrEL；聚氧乙烯甘油三羧酸酯）胶束将菌氯溶液稀释到相同的培养基中进行比较。CrEL通常会减少聚集（如吸收和荧光所示），并将活性提高10倍（取决于细菌氯），尽管它会降低细胞摄取。经10 J cm−2近红外光照24 h后，PDT对HeLa人癌细胞的活性顺序为（NC）2BC - pd (LD50 = 25 nm) > (NC)2BC > (NC)2BC - zn≈BC。亚细胞定位确定在内质网，线粒体和溶酶体，取决于细菌氯。（NC） 2BC-Pd显示pdt介导的线粒体和溶酶体损伤，并通过羟基苯基荧光素探针检测到羟基自由基的最大产生。氰基取代基的加入为提高细菌氯作为PDT光敏剂的光活性和光稳定性提供了一个很好的基序。
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 Cremophor EL (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 24 h incubation and illumination with 10 J cm−2 of near-infrared (NIR) light is (NC)2BC–Pd (LD50 = 25 nm) > (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.
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影响因子：
3.5
作者：
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