Enhanced antitumor efficacy of cisplatin for treating ovarian cancer in vitro and in vivo via transferrin binding
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Huifang Peng1,*, Hongwei Jin2,*, Huiqin Zhuo3,4 and Heqing Huang1,5,6
1State Key Laboratory of Stress Cell Biology, School of Life Science, Xiamen University, Xiamen, Fujian 361004, China
2Xiamen Center of Clinical Laboratory, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China
3Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China
4Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen University, Xiamen, Fujian 361004, China
5State Key Laboratory of Marine Environmental Science, College of Oceanography and Environmental Science, Xiamen University, Xiamen, Fujian 361004, China
6The 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
Heqing Huang, email: [email protected]
Huiqin Zhuo, email: [email protected]
Keywords: cisplatin, transferrin, targeted drug delivery, ovarian cancer, antitumor treatment
Received: May 12, 2016 Accepted: April 02, 2017 Published: April 21, 2017
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.
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