Zhu Sizhe, Yao Si, Wu Fengshou, Jiang Lijun, Wong Ka-Leung, Zhou Ji, Wang Kai
Key Laboratory for Green Chemical Process of Ministry of Education, Wuhan Institute of Technology, Wuhan, P. R. China.
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, P. R. China.
Org Biomol Chem. 2017 Jul 21;15(27):5764-5771. doi: 10.1039/c7ob01003f. Epub 2017 Jun 29.
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.
细胞器和细胞核双靶向抗癌药物正越来越多地用于高效癌症治疗，因为它们可以攻击肿瘤细胞的两个重要位点。在这项工作中，我们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均以插入结合模式有效地与DNA结合。光照后，具有低暗细胞毒性的Pt-Por-RB可通过光动力疗法快速产生活性单线态氧以损伤肿瘤细胞。与Me-Por-RB相比，Pt-Por-RB不仅被内化到细胞器中，还被内化到HeLa细胞的细胞核中，这可能是由于铂配合物的存在，这是使用共聚焦激光扫描显微镜分析得出的。因此，结合细胞器和细胞核双靶向特性以及单线态氧的高效产生，Pt-Por-RB对肿瘤细胞显示出显著的治疗活性。
