Water-soluble polymer conjugates of ZnPP for photodynamic tumor therapy
Water-soluble polymer conjugates of ZnPP for photodynamic tumor therapy
复制标题
DOI：
10.1021/bc060158u
复制
发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Roeder, B.
中科院分区：
文献类型：
--
作者：
Regehly, M.;Greish, K.;Roeder, B.
锌原卟啉（ZnPP）是一种很有前途的癌症治疗药物。已知它能抑制血红素加氧酶-1 (HO-1)，从而抑制胆绿素/胆红素的产生，同时降低抗氧化能力。因此，据报道，体内肿瘤生长受到显著抑制。最近的研究结果还表明，ZnPP在可见光照射下可以有效地生成反应性单重态氧。在本报告中，我们描述了水溶性ZnPP聚合物偶联物作为光动力治疗实体肿瘤的新化合物的光敏能力。聚合物偶联使得ZnPP可溶于水，从而使其水溶液可以注射。ZnPP衍生物的细胞摄取和光生物活性已经在体外用人类t细胞白血病细胞系进行了测试，结果表明在有氧条件下，SMA-ZnPP的光毒性最强，其次是PEG-ZnPP。
Zn-protoporphyrin (ZnPP) is a promising candidate for cancer therapy. It is known to inhibit heme-oxygenase-1 (HO-1), resulting in suppressed biliverdin/bilirubin production accompanying lowered antioxidative capacity. As a consequence, a significant suppression of tumor growth in vivo was reported. Recent findings also showed that ZnPP efficiently generated reactive singlet oxygen under illumination of visible light. In the present report, we describe the photosensitizing capabilities of water-soluble polymer conjugates of ZnPP as novel compounds for photodynamic therapy against solid tumors. The polymer conjugation made ZnPP water-soluble, thus possible for injection for its aqueous solution. The cellular uptake and photobiological activity of ZnPP derivatives have been tested using a human T-cell leukemia cell line in vitro and demonstrated most potent phototoxic effects of SMA-ZnPP followed by PEG-ZnPP under aerobic conditions.