Herceptin–Platinum(II) Binding Complexes: Novel Cancer-Cell-Specific Agents

✍ Scribed by Jian Gao; Ya Guang Liu; Renbin Liu; Ralph A. Zingaro

• Book ID: 102804163
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 640 KB
• Volume: 3
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200700349

✦ Synopsis

Abstract

We report a new series of Herceptin–platinum(II) binding complexes, Her–__n__LPt^II^ (Her denotes Herceptin; L denotes diamino ligands and L=L1–L4; n=1, 5, or 10). Solution chemistry studies have shown that these complexes are stable under physiological conditions (pH 7.4 in PBS). The platinum(II) compound L1Pt^II^Cl~2~ inhibits the growth of a panel of human cancer cell lines at sub‐micromolar concentrations. Remarkable cancer‐cell‐specific cytotoxicity was observed with Her–__n__L1Pt^II^ (n=1, 5, 10) toward Her2/neu‐overexpressing cancer cells (SK‐BR‐3 and SK‐OV‐3) over normal fibroblast cells. Annexin V apoptosis assays in SK‐BR‐3 and low‐Her2/neu‐expressing MCF‐7 breast cancer cells further confirmed the critical role of Herceptin with this cancer‐cell‐specific agent. It was also found that the L1Pt^II^Cl~2~ complex is an efficient regulator of the apoptotic genes Bcl‐2 in the treated SK‐BR‐3 cells. Also, enhanced regulatory effects were observed in Her–10L1Pt^II^. Taken together, this study suggests a new approach for the development of mAb–platinum(II)‐based targeting agents for the treatment of human cancers.