Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells.
Syntheses and Photodynamic Activity of Pegylated Cationic Zn(II)-Phthalocyanines in HEp2 Cells.
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DOI：
10.7150/thno.4547
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发表时间：
2012
期刊：
影响因子：
12.4
通讯作者：
Vicente MG
中科院分区：
文献类型：
--
作者：
Ongarora BG;Hu X;Verberne-Sutton SD;Garno JC;Vicente MG
双阳离子锌(II)-酞菁(ZnPcs)是一种很有前途的光敏剂，可用于癌症的光动力治疗(PDT)和病毒和细菌的光灭活。光敏剂的聚乙二醇化一般会增强它们的水溶性和肿瘤细胞的聚集。通过将低相对分子质量的聚乙二醇基连接到预制的聚乙二醇大环上，或通过与聚乙二醇化邻苯二甲腈的混合缩合反应，合成了一系列聚乙二醇化的双阳离子锌Pcs。所有聚乙二醇化的ZnPcs在极性有机溶剂中高度溶解，但不溶于水；它们在DMF中具有680 nm的强Q吸收，荧光量子产率约为0.2。非聚乙二醇化的双阳离子ZnPc 6a形成了大的聚集体，原子力显微镜观察到了聚集体的存在。在人肝癌HEp2细胞中研究了所有阳离子锌的细胞毒性、细胞摄取和亚细胞分布。最具光毒性的化合物是α取代的PC。其中，PC 4a和16a是最有效的(IC_(50)约10μM，1.5J/cm~2)，部分原因是在这些大环中存在聚乙二醇基和两个接近的正电荷(由一个乙烯基团隔开)。β取代的ZcPcs6b和4b在HEp2细胞内积累最多，但具有较低的光毒性(IC_(50)>；100μM，1.5J/cm~2)，这可能是因为与α取代的PC相比，它们的环电子密度更低，构象更广泛。结果表明，Pc大环的电荷分布和阳离子ZnPcs的胞内定位是决定其光动力学活性的主要因素。
Di-cationic Zn(II)-phthalocyanines (ZnPcs) are promising photosensitizers for the photodynamic therapy (PDT) of cancers and for photoinactivation of viruses and bacteria. Pegylation of photosensitizers in general enhances their water-solubility and tumor cell accumulation. A series of pegylated di-cationic ZnPcs were synthesized from conjugation of a low molecular weight PEG group to a pre-formed Pc macrocycle, or by mixed condensation involving a pegylated phthalonitrile. All pegylated ZnPcs were highly soluble in polar organic solvents but were insoluble in water; they have intense Q absorptions centered at 680 nm and fluorescence quantum yields of ca. 0.2 in DMF. The non-pegylated di-cationic ZnPc 6a formed large aggregates, which were visualized by atomic force microscopy. The cytotoxicity, cellular uptake and subcellular distribution of all cationic ZnPcs were investigated in human carcinoma HEp2 cells. The most phototoxic compounds were found to be the α-substituted Pcs. Among these, Pcs 4a and 16a were the most effective (IC50 ca. 10 μM at 1.5 J/cm2), in part due to the presence of a PEG group and the two positive charges in close proximity (separated by an ethylene group) in these macrocycles. The β-substituted ZcPcs 6b and 4b accumulated the most within HEp2 cells but had low photocytoxicity (IC50 > 100 μM at 1.5 J/cm2), possibly as a result of their lower electron density of the ring and more extended conformations compared with the α-substituted Pcs. The results show that the charge distribution about the Pc macrocycle and the intracellular localization of the cationic ZnPcs mainly determine their photodynamic activity.
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影响因子：
3.2
作者：
Bai, Ming;Lo, Pui-Chi;Ng, Dennis K. P.
通讯作者：
Ng, Dennis K. P.
影响因子：
3.9
作者：
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通讯作者：
Ahsen, Vefa
DOI：
10.2174/187152107780361652
发表时间：
2007-04-01
期刊：
Anti-Infective Agents in Medicinal Chemistry
影响因子：
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作者：
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通讯作者：
Coppellotti, Olimpia
影响因子：
2.4
作者：
Krueger, T;Altermatt, HJ;Ris, HB
通讯作者：
Ris, HB
DOI：
10.1016/s1011-1344(96)07416-7
发表时间：
1997-02-01
影响因子：
5.4
作者：
Dummin, H;Cernay, T;Zimmermann, HW
通讯作者：
Zimmermann, HW