Journal
ONCOTARGET
Volume 8, Issue 28, Pages 45597-45611Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.17316
Keywords
cisplatin; transferrin; targeted drug delivery; ovarian cancer; antitumor treatment
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Funding
- National Natural Scientific Foundation of China [81370048, 30870515]
- Natural Science Foundation of Fujian Province [2016J01631, 2016-ZQN-88]
- Key Projects for Technology Plan of Xiamen Province in China [3502Z20100002, 3502Z201262]
- PCSIRT Project, China [IRT0941]
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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 nudemice 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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