Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles.
Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles.
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DOI：
10.1039/c5nr00795j
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发表时间：
2015-08
期刊：
影响因子：
6.7
通讯作者：
A. Lavado;Veeren M. Chauhan;Amer Alhaj Zen;F. Giuntini;D. Rhodri E. Jones;R. Boyle;A. Beeby;Weng-Chyn Chan;J. Aylott
中科院分区：
文献类型：
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作者：
A. Lavado;Veeren M. Chauhan;Amer Alhaj Zen;F. Giuntini;D. Rhodri E. Jones;R. Boyle;A. Beeby;Weng-Chyn Chan;J. Aylott
通过用锌（II）卟啉光敏剂官能化聚丙烯酰胺纳米颗粒，合成了能够产生受控量的细胞内活性氧（ROS）的纳米颗粒，其推进了氧化应激和细胞通讯的研究。通过（1）产生用不同百分比的Zn（II）卟啉官能化的纳米颗粒和（2）调节激发光的剂量数以内化纳米颗粒，在人间充质干细胞（hMSC）中证明了受控的ROS产生。研究发现，用增加比例的锌（II）卟啉功能化的纳米颗粒和大量激发光照射来挑战hMSC会产生更大量的活性氧。一种新的染料，这是转化为荧光7-羟基-4-三氟甲基-香豆素在过氧化氢的存在下，提供了一个间接的指示累积ROS的生产。线粒体膜电位的监测，以研究增加细胞内的ROS产生的破坏性影响。纳米颗粒处理的hMSC的流式细胞术分析表明，用激发光照射发出受控凋亡细胞死亡的信号，而不是不受控制的坏死细胞死亡。增加细胞内活性氧的产生并没有诱导hMSC传代培养的表型变化。
Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(II) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(II) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(II) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.