Human Chorionic Gonadotropin Polypeptide Nanoparticle Drug Delivery System Improves Methotrexate Efficacy in Gestational Trophoblastic Neoplasia in vitro

Abstract

Qing Cong,1,2,* Ling Lin,1,3,* Biao Qi,4 Congjian Xu,1,2 Xiaoyan Zhang1,2 1Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China; 3Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, People’s Republic of China; 4Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Congjian Xu; Xiaoyan ZhangDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of ChinaEmail [email protected]; [email protected]: To alleviate the sufferings of the chemotherapy patients, we developed a novel active targeted therapeutic system and showed its potential as a promising drug delivery strategy.Methods: We utilized the human chorionic gonadotropin (HCG) ligand-receptor mediation to make an actively targeted drug delivery system with optimal HCG polypeptide fragment as target head base, polyethylene glycol–polylactic acid copolymers as nanometer materials to load chemotherapy drug methotrexate (MTX), to highly selectively deliver MTX into choriocarcinoma lesions, and to investigate the efficacy, targeting and tolerability of the complex in vitro experiments.Results: Our data show that choriocarcinoma cell lines JEG-3 and JAR exhibited high expression levels of HCG receptor, peptide HCGβ 81-95 specifically bonded to HCG receptor-positive cells and HCG81-NP efficiently delivered MTX to choriocarcinoma cells. HCG81-NP-MTX inhibited cell proliferation and reduced G0/G1 to S phase transition in JEG-3 and JAR cells.Conclusion: We designed an active targeting therapy system of choriocarcinoma, significantly improved chemotherapy efficacy in vitro, and provided a theoretical basis for the treatment of malignant trophoblastic tumors.Keywords: choriocarcinoma, human chorionic gonadotropin, nanoparticle, methotrexate, cell proliferation

Keywords

• choriocarcinoma
• human chorionic gonadotropin
• nanoparticle
• methotrexate
• cell proliferation