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

• Published in: Oncotarget Vol. 8; no. 28; pp. 45597 - 45611
• Main Authors: Peng, Huifang, Jin, Hongwei, Zhuo, Huiqin, Huang, Heqing
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 11.07.2017
• Subjects: Animals; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cell Line, Tumor; Cisplatin - metabolism; Cisplatin - pharmacology; Cisplatin - therapeutic use; Disease Models, Animal; Female; Humans; Mice; Native Polyacrylamide Gel Electrophoresis; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Protein Binding; Research Paper; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transferrin - chemistry; Transferrin - metabolism; Xenograft Model Antitumor Assays; transferrin; targeted drug delivery; cisplatin; ovarian cancer; antitumor treatment
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.17316

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.