Synthesis and characterization of mono-, di-, and tri-poly(ethylene glycol) chlorin e6 conjugates for the photokilling of human ovarian cancer cells.
Synthesis and characterization of mono-, di-, and tri-poly(ethylene glycol) chlorin e6 conjugates for the photokilling of human ovarian cancer cells.
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DOI：
10.1021/jo301889s
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发表时间：
2012-12-07
期刊：
影响因子：
--
通讯作者：
Greer A
中科院分区：
文献类型：
--
作者：
Kimani S;Ghosh G;Ghogare A;Rudshteyn B;Bartusik D;Hasan T;Greer A
合成了聚乙二醇化二氢卟酚e6光敏剂，其中三甘醇在酯键处连接，用于在173-位的1：1缀合物、在152-和173-位的2：1缀合物以及在131-、152-和173-位的3：1缀合物。研究了这些二氢卟酚敏化剂的水解稳定性、溶解度以及卵巢OVCAR-5癌细胞摄取、定位和光毒性。增加单-、二-和三-PEG二氢卟酚缀合物中的PEG基团的数量增加了水溶性和对水解的敏感性以及卵巢癌细胞的摄取。PEG二氢卟酚结合物在细胞质和线粒体中积累，但不在溶酶体中积累。较高的光毒性大致与较高数量的PEG基团相关，其中三PEG二氢卟酚缀合物显示出该系列中最好的总体卵巢癌细胞光杀伤。单线态氧寿命，溶剂氘代，叠氮离子和D-甘露醇的添加剂的影响进行了检查，以帮助澄清的光杀伤机制。二-和三-PEG二氢卟酚共轭物的II型（单线态氧）光敏化机制被建议，然而，一个更复杂的过程，部分基于I型（自由基或自由基离子）的机制被建议为母体二氢卟酚e6和单-PEG二氢卟酚共轭物。
Pegylated chlorin e6 photosensitizers were synthesized with triethylene glycol attached at the ester bond(s) for a 1:1 conjugate at the 173-position, a 2:1 conjugate at the 152- and 173-positions, and a 3:1 conjugate at the 131-, 152-, and 173-positions. These chlorin sensitizers were studied for hydrolytic stability, solubility, as well as ovarian OVCAR-5 cancer cell uptake, localization, and phototoxicity. Increasing numbers of the PEG groups in the mono-, di-, and tri-PEG chlorin conjugates increased the water solubility and sensitivity to hydrolysis and uptake into the ovarian cancer cells. The PEG chlorin conjugates accumulated in the cytoplasm and mitrochondria, but not in lysosomes. Higher phototoxicity was roughly correlated with higher numbers of PEG groups, with the tri-PEG chlorin conjugate showing the best overall ovarian cancer cell photokilling of the series. Singlet oxygen lifetimes, solvent deuteration, and the effects of additives azide ion and D-mannitol were examined to help clarify the photokilling mechanisms. A Type-II (singlet oxygen) photosensitized mechanism is suggested for the di- and tri-PEG chlorin conjugates, however, a more complicated process based in part on a Type-I (radicals or radical ions) mechanism is suggested for the parent chlorin e6 and the mono-PEG chlorin conjugate.
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影响因子：
3.6
作者：
Bartusik, Dorota;Aebisher, David;Greer, Alexander
通讯作者：
Greer, Alexander
影响因子：
3.3
作者：
Hargus, Jodie A.;Fronczek, Frank R.;Smith, Kevin M.
通讯作者：
Smith, Kevin M.
影响因子：
4.7
作者：
Fleming, AB;Haverstick, K;Saltzman, WM
通讯作者：
Saltzman, WM
DOI：
10.1016/j.jphotobiol.2006.01.011
发表时间：
2006-07-03
影响因子：
5.4
作者：
Hirohara, Shiho;Obata, Makoto;Yano, Shigenobu
通讯作者：
Yano, Shigenobu
影响因子：
4
作者：
Lavis, Luke D.
通讯作者：
Lavis, Luke D.