Synthesis and evaluation of cationic bacteriochlorin amphiphiles with effective in vitro photodynamic activity against cancer cells at low nanomolar concentration.
Synthesis and evaluation of cationic bacteriochlorin amphiphiles with effective in vitro photodynamic activity against cancer cells at low nanomolar concentration.
复制标题
DOI：
10.1142/s108842461250126x
复制
发表时间：
2013-01
影响因子：
1.5
通讯作者：
Hamblin MR
中科院分区：
文献类型：
--
作者：
Sharma SK;Krayer M;Sperandio FF;Huang L;Huang YY;Holten D;Lindsey JS;Hamblin MR
由于细菌绿素在光谱的近红外（NIR）区域中的强烈吸收，细菌绿素是作为光动力疗法（PDT）的光敏剂的有吸引力的候选物，其中光透射通过组织是最大的。许多天然存在的细菌绿素由于偶然的大气氧化而固有地不稳定。从头合成提供了在每个还原的吡咯环中含有偕二甲基基团以增加抗氧化稳定性的菌绿素。在这里，三个新的合成菌绿素，每个轴承一个单一的侧链含有一个或两个正电荷，研究了它们在体外PDT活性对HeLa人类癌细胞。所有的菌绿素在低纳摩尔浓度下用近红外光激活时都是活性的;那些带有单个正电荷的菌绿素表现出更快的吸收和更高的活性。细胞器特异性荧光探针显示细菌绿素定位于线粒体、溶酶体和内质网。细胞形态学和核固缩显示细胞通过凋亡死亡。两者合计，结果显示了适当的外围组的光敏剂的有效PDT应用的重要性。
Bacteriochlorins are attractive candidates as photosensitizers for photodynamic therapy (PDT) due to their intense absorption in the near-infrared (NIR) region of the spectrum where light transmission through tissue is maximal. Many naturally occurring bacteriochlorins are inherently unstable due to adventitious atmospheric oxidation. A de novo synthesis affords bacteriochlorins that contain a geminal dimethyl group in each reduced pyrrole ring to increase stability against oxidation. Here, three new synthetic bacteriochlorins, each bearing a single side-chain containing one or two positive charges, were investigated for their in vitro PDT activity against HeLa human cancer cells. All bacteriochlorins were active at low nanomolar concentration when activated with NIR light; those bearing a single positive charge exhibited faster uptake and higher activity. The bacteriochlorins were localized in mitochondria, lysosomes and endoplasmic reticulum as shown by organelle specific fluorescent probes. Cell death was via apoptosis as shown by cell morphology and nuclear condensation. Taken together, the results show the importance of appropriate peripheral groups about a photosensitizer for effective PDT applications.