Enhanced antitumor efficacy of cisplatin for treating ovarian cancer in vitro and in vivo via transferrin binding

// Huifang Peng 1, * , Hongwei Jin 2, * , Huiqin Zhuo 3, 4 and Heqing Huang 1, 5, 6 1 State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, Xiamen, Fujian 361004, China 2 Xiamen Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China 3 Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China 4 Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen University, Xiamen, Fujian 361004, China 5 State Key Laboratory of Marine Environmental Science, College of Oceanography and Environmental Science, Xiamen University, Xiamen, Fujian 361004, China 6 The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry & Chemical Engineering, Xiamen University, Xiamen, Fujian 361004, China * These authors have contributed equally to this work Correspondence to: Heqing Huang, email: hqhuang@xmu.edu.cn Huiqin Zhuo, email: zhuohuiqin@xmu.edu.cn Keywords: cisplatin, transferrin, targeted drug delivery, ovarian cancer, antitumor treatment Received: May 12, 2016     Accepted: April 02, 2017     Published: April 21, 2017 ABSTRACT Cisplatin is a widely used anticancer drug, while non-targeted delivery, development of drug resistance, and serious side effects significantly limit its clinical use. In order to improve the tumor-targeting properties of cisplatin, transferrin (Tf) was employed as a carrier to transfer cisplatin into cancer cells via transferrin receptor 1 (TfR1) mediated endocytosis. The binding ability of cisplatin and Tf could be improved by pretreating Tf with 10% ethanol, and the binding number of cisplatin for each Tf molecule could reach to 40 without structural or functional impairment of Tf. The Tf-cisplatin complex could be delivered into human ovarian carcinoma cells high efficiently. In tumor-bearing nude-mice model, the Tf-cisplatin complex inhibited tumor growth in vivo more effectively than free cisplatin, with less toxicity in other tissues. Tumor targeting efficiency of the Tf-cisplatin complex was supported by in vivo and ex vivo imaging and platinum residues detected in each ex vivo organ. These data suggested that Tf-cisplatin  was more effective and less drug-resistance than cisplatin, with targeting to tumor cells. Therefore, Tf-mediated delivery of cisplatin is a potential strategy for targeted delivery into tumor cells.