Chen Juan-Juan, Huang Yi-Zhen, Song Mei-Ru, Zhang Zhi-Hong, Xue Jin-Ping
National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, and Fujian Engineering Research Center of Functional Materials, College of Chemistry, Fuzhou University, Fuzhou, 350116, China.
Fuzhou General Hospital of Nanjing Military Command, Fuzhou, 350005, China.
ChemMedChem. 2017 Sep 21;12(18):1504-1511. doi: 10.1002/cmdc.201700384. Epub 2017 Sep 6.
Small-molecular-target-based photodynamic therapy-a promising targeted anticancer strategy-was developed by conjugating zinc(II) phthalocyanine with a small-molecular-target-based anticancer drug. To prevent self-aggregation and avoid problems of phthalocyanine isomerization, two silicon phthalocyanines di-substituted axially with erlotinib have been synthesized and fully characterized. These conjugates are present in monomeric form in various solvents as well as culture media. Cell-based experiments showed that these conjugates localize in lysosomes and mitochondria, while maintaining high photodynamic activities (IC values as low as 8 nm under a light dose of 1.5 J cm ). With erlotinib as the targeting moiety, two conjugates were found to exhibit high specificity for EGFR-overexpressing cancer cells. Various poly(ethylene glycol) (PEG) linker lengths were shown to have an effect on the photophysical/photochemical properties and on in vitro phototoxicity.
基于小分子靶点的光动力疗法——一种有前景的靶向抗癌策略——是通过将锌（II）酞菁与一种基于小分子靶点的抗癌药物偶联而开发的。为了防止自聚集并避免酞菁异构化问题，已经合成并全面表征了两种轴向用厄洛替尼二取代的硅酞菁。这些共轭物在各种溶剂以及培养基中以单体形式存在。基于细胞的实验表明，这些共轭物定位于溶酶体和线粒体，同时保持高光动力活性（在1.5 J/cm²的光剂量下，IC值低至8 nM）。以厄洛替尼作为靶向部分，发现两种共轭物对表皮生长因子受体（EGFR）过表达的癌细胞具有高特异性。结果表明，各种聚乙二醇（PEG）连接子长度对光物理/光化学性质以及体外光毒性有影响。
