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.
Highlights
Ovarian cancer is the leading cause of death from gynaecologic cancer, and it is estimated that 22,280 new diagnoses and 14,240 deaths from this neoplasm will occur in United States in 2016 [1]
Identification and purity of isolated proteins were determined by native polyacrylamide gel electrophoresis (PAGE) and MALDI-TOF-MS analysis
Proteins were extracted a second time with native gradient PAGE, resulting in detection of a single, pure band, which was removed for preparation of peptide mass fingerprinting
Summary
Ovarian cancer is the leading cause of death from gynaecologic cancer, and it is estimated that 22,280 new diagnoses and 14,240 deaths from this neoplasm will occur in United States in 2016 [1]. Standard treatment is platinum (Pt)-based chemotherapy and surgical debulking of the tumor. There is a high proportion (~ 70%) of advanced stage cases at diagnosis, and the overall 5-year survival rate is less than 40% across all stages [2]. Ovarian cancers overall are comprised of a variety of tumor types with different histopathological features and biological behaviour. Most ovarian cancer patients present with advanced-stage disease, response to front-line Ptbased chemotherapy is high, of the order of 75% [3]. Cisplatin is one of the most actively used drugs for the treatment of ovarian cancer, and the resistance is seen in patients during treatment [5]. Strategies for altering the entry of cisplatin into cancer cells may be helpful for reducing side effects and resistance while increasing therapeutic efficacy
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