铂类抗癌药物是少数几种对肝癌有效的药物之一，用于肝动脉灌注化疗和肝动脉介入栓塞化疗。然而，它们的临床应用还存在着两大缺陷，即毒副反应和耐药性，主要原因是药物对癌细胞/组织缺乏选择性。靶向给药是降低药物毒性和提高疗效的最有效方法之一，是抗癌药物发展的重要方向。胆酸为肝细胞合成胆汁酸的基本原料，主要被肝细胞摄取和利用，对肝组织具有很高的选择性，体内给药后大部分聚集在肝内，是一个理想的药物靶向肝的载体。. 本项目拟采用胆酸作为铂类药物的肝靶向载体，通过一种新的偶联方式和技术，将胆酸通过稳定的酰胺键连接在1,1-环丁二羧酸根的3位碳上，再与已批准上市的铂类药物的药效基团配位，合成出一类以胆酸为运转分子的肝靶向Pt(II)抗癌配合物，以期获得一种治疗肝癌的新型候选药物。项目的主要研究内容包括：目标铂配合物的合成、结构表征、靶向性研究、体内外抗肝癌的疗效评价和构效关系探讨。

Platinum-based drugs represented by cisplatin, carboplatin and oxaliplatin are among a few chemotherapeutic agents effective against the liver cancer. However, the efficacy and applicability of platinum drugs are heavily restricted by severe systemic toxicities and drug resistance, due to their poor tumor-specificity. Nowadays, Drug targeting is a highly active field of research for anticancer drugs, for it can deliver the drugs directly to tumour sites, resulting in the decrease of drug-related toxicity as well as the increase of chemotherapy efficiency. Cholic acid, as a fundamental component for synthesis of bolic acid in liver organ, is up-taken and used mainly by hepatocytes, leading to the suggestion that this steroid could be used as carrier molecules to shuttle drugs to the liver.. With a view to using cholic acid as shuttles for delivering platinum anti-drugs to the liver tumor site, the present research program is to adopt a new coupling way for attaching cholic acid to the pharmacophores of clinically approved platinum drugs via cyclobutane-1,1-dicarboxylate as the linker, and to develop new cholic acid-mediated platinum anticancer complexes for targeting the liver tumor. The work of the present program mainly involves synthesis, liver targeting profile and anticancer activity of the designed platinum complexes. In addition, possible structure-activity relationship will also be explored.