Intracellular distribution and intracellular dynamics of a spin-labeled analogue of doxorubicin by fluorescence and EPR spectroscopy
Intracellular distribution and intracellular dynamics of a spin-labeled analogue of doxorubicin by fluorescence and EPR spectroscopy
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DOI：
10.1021/js970271g
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发表时间：
1998-03-01
影响因子：
3.8
通讯作者：
Pitina, L
中科院分区：
文献类型：
--
作者：
Rapoport, N;Pitina, L
荧光光谱显示阿霉素(DOX)及其顺磁性类似物Ruboxyl(Rb)在细胞内的分布有显著差异。荧光猝灭实验表明，通过在DOX分子第14位引入顺磁性标记来修饰蒽环素结构，可减少DNA结合并增强对磷脂膜的分配。Rb进入细胞膜的比例越高，其胞内荧光强度越强。此外，Rb分子上的顺磁性标记为EPR研究药物在细胞内的分布和动力学提供了独特的机会。观察到的含药细胞在其生命周期中的EPR谱的变化表明插层药物的逐渐释放，细胞膜的流态化，或两者兼而有之。
Fluorescence spectroscopy revealed a dramatic difference between the intracellular distributions of doxorubicin (DOX) and its paramagnetic analogue, ruboxyl (Rb). Modification of the anthracyclin structure by introduction of a paramagnetic label at position 14 in the DOX molecule resulted in reduced DNA binding and enhanced partitioning into phospholipid membranes, as evidenced by the fluorescence-quenching experiments. Higher partitioning into cell membranes resulted in stronger intracellular fluorescence of Rb. In addition, a paramagnetic label on the Rb molecule provided a unique opportunity for an EPR investigation of the drug's intracellular distribution and dynamics. The observed changes in the EPR spectra of drug-containing cells during their life cycle suggested either a progressive release of the intercalated drug, cell membrane fluidization, or both.