Department of Chemistry and ‡School of Life Sciences, The Chinese University of Hong Kong , Shatin, N.T., Hong Kong, China.
J Med Chem. 2013 Nov 14;56(21):8475-83. doi: 10.1021/jm4009168. Epub 2013 Oct 22.
Two folate-conjugated diiododistyryl boron dipyrromethenes have been prepared and characterized with various spectroscopic methods. These conjugates exhibit higher photocytotoxicity toward the KB human nasopharyngeal carcinoma cells, which have high expression of folate receptors when compared with the MCF-7 human breast adenocarcinoma cells, which have low expression of folate receptors. The difference in photocytotoxicity for these two cell lines is particularly large for the conjugate with a shorter oligoethylene glycol linker (compound 11a) as a result of its higher cellular uptake and slightly lower aggregation tendency. Its IC50 value toward KB cells (0.06 μM) is 43-fold lower than that for MCF-7 cells, while the difference is only 6-fold for the analogue with a longer linker (compound 11b). The length of the spacer also affects their subcellular localization. While compound 11a shows high affinity toward the endoplasmic reticulum of KB cells, conjugate 11b is mainly localized in the lysosomes.
两种叶酸偶联的二碘二苯乙烯硼二吡咯甲川染料已通过各种光谱方法进行了制备和表征。与叶酸受体低表达的 MCF-7 人乳腺癌细胞相比，这些化合物对高表达叶酸受体的 KB 人鼻咽癌细胞表现出更高的光细胞毒性。对于具有较短聚乙二醇接头（化合物 11a）的缀合物，两种细胞系的光细胞毒性差异特别大，这是由于其更高的细胞摄取率和稍低的聚集趋势所致。其对 KB 细胞的 IC50 值（0.06 μM）比 MCF-7 细胞低 43 倍，而对于具有较长接头的类似物（化合物 11b），差异仅为 6 倍。间隔物的长度也会影响它们的亚细胞定位。虽然化合物 11a 对 KB 细胞的内质网具有高亲和力，但缀合物 11b 主要定位于溶酶体中。
