Platinated porphyrin as a new organelle and nucleus dual-targeted photosensitizer for photodynamic therapy.
Platinated porphyrin as a new organelle and nucleus dual-targeted photosensitizer for photodynamic therapy.
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DOI：
10.1039/c7ob01003f
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发表时间：
2017-07
影响因子：
3.2
通讯作者：
Sizhe Zhu;Si Yao;Fengshou Wu;Lijun Jiang;Ka‐Leung Wong;Ji Zhou;Kai Wang
中科院分区：
文献类型：
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作者：
Sizhe Zhu;Si Yao;Fengshou Wu;Lijun Jiang;Ka‐Leung Wong;Ji Zhou;Kai Wang
细胞器和细胞核双靶向抗癌药物正越来越多地用于有效的癌症治疗，因为它们可以攻击肿瘤细胞的双重重要部位。本文合成并表征了两种新的卟啉化合物Pt-Por-RB和Me-Por-RB。光谱滴定结果表明，Pt-Por-RB和Me-Por-RB均以嵌入结合方式与DNA有效结合。在照射后，具有低暗细胞毒性的Pt-Por-RB可以通过光动力学治疗过程快速产生单线态氧来损伤肿瘤细胞。与Me-Por-RB相比，Pt-Por-RB不仅内化于细胞器中，而且还内化于HeLa细胞的细胞核中，可能是由于铂络合物的存在，如使用共聚焦激光扫描显微镜分析的。因此，Pt-Por-RB结合细胞器和细胞核的双重靶向特性和高效率的单线态氧产生，显示出对肿瘤细胞的显著治疗活性。
Organelle and nucleus dual-targeted anticancer drugs are being increasingly used for efficient cancer therapy as they can attack the double vital sites of tumor cells. In this work, we synthesized and characterized two new porphyrin compounds Pt-Por-RB and Me-Por-RB. The spectral titration results suggest that both Pt-Por-RB and Me-Por-RB bind to DNA efficiently in an intercalation binding mode. Upon irradiation, Pt-Por-RB with low dark-cytotoxicity can rapidly generate singlet oxygen to damage the tumor cells through the process of photodynamic therapy. Compared with Me-Por-RB, Pt-Por-RB was not only internalized in the organelles, but also in the nuclei of HeLa cells, probably due to the presence of platinum complexes, as analyzed using the confocal laser scanning microscope. Thus, with the combination of organelle and nucleus dual-targeting property and high efficiency of singlet oxygen generation, Pt-Por-RB showed a significant therapeutic activity against tumor cells.