Michaelis Martin, Langer Klaus, Arnold Sonja, Doerr Hans-Wilhelm, Kreuter Jörg, Cinatl Jindrich
Institut für Medizinische Virologie, Zentrum der Hygiene, Klinikum der J.W. Goethe-Universität, Paul Ehrlich Str. 40, 60596 Frankfurt am Main, Germany.
Biochem Biophys Res Commun. 2004 Oct 29;323(4):1236-40. doi: 10.1016/j.bbrc.2004.08.223.
The chelating agent diethylenetriaminepentaacetic acid (DTPA) inhibits human cytomegalovirus replication. Since chelating agents are known to exhibit anti-cancer effects, DTPA-induced cytotoxicity was evaluated in breast cancer cells (MCF-7) and neuroblastoma cells (UKF-NB-3). DTPA inhibited cancer cell growth in threefold lower concentrations compared to human foreskin fibroblasts (HFF). Antiviral and anti-cancer activity of chelating agents is caused by intracellular complexation of metal ions. DTPA, an extracellular chelator, was covalently coupled to human serum albumin (HSA) molecules, HSA nanoparticles (HSA-NP), gelatin type B (GelB) molecules, and GelB nanoparticles (GelB-NP) to increase cellular uptake. Coupling of DTPA to drug carrier systems increased its cytotoxic and antiviral activity by 5- to 8-fold. Confocal laser scanning microscope examination revealed uptake of DTPA-HSA-NP in UKF-NB-3 cells and HFF. Therefore, coupling of DTPA to protein-based drug carrier systems increases its antiviral and anti-cancer activity probably by mediating cellular uptake.
螯合剂二乙烯三胺五乙酸（DTPA）可抑制人巨细胞病毒复制。由于已知螯合剂具有抗癌作用，因此在乳腺癌细胞（MCF-7）和神经母细胞瘤细胞（UKF-NB-3）中评估了DTPA诱导的细胞毒性。与人类包皮成纤维细胞（HFF）相比，DTPA在浓度低三倍的情况下就能抑制癌细胞生长。螯合剂的抗病毒和抗癌活性是由金属离子的细胞内络合作用引起的。DTPA是一种细胞外螯合剂，它与人类血清白蛋白（HSA）分子、HSA纳米颗粒（HSA-NP）、B型明胶（GelB）分子以及GelB纳米颗粒（GelB-NP）共价偶联，以增加细胞摄取。将DTPA与药物载体系统偶联可使其细胞毒性和抗病毒活性提高5至8倍。共聚焦激光扫描显微镜检查显示，UKF-NB-3细胞和HFF摄取了DTPA-HSA-NP。因此，将DTPA与基于蛋白质的药物载体系统偶联可能通过介导细胞摄取来提高其抗病毒和抗癌活性。
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