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

Qing Cong; Ling Lin; Biao Qi; Congjian Xu; Xiaoyan Zhang

doi:10.2147/CMAR.S279831

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

Cancer Manag Res. 2021 Feb 18:13:1699-1708. doi: 10.2147/CMAR.S279831. eCollection 2021.

Authors

Qing Cong^#^{1

2}, Ling Lin^#^{1

3}, Biao Qi⁴, Congjian Xu^{1

2}, Xiaoyan Zhang^{1

2}

Affiliations

¹ Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.
² Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People's Republic of China.
³ Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, People's Republic of China.
⁴ Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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 HCGβ81-95 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: cell proliferation; choriocarcinoma; human chorionic gonadotropin; methotrexate; nanoparticle.

Grants and funding

This work was supported by Health Commission Project of Shanghai Municipality (201344095) and Clinical Research Project of Shanghai Municipal Health Commission (20204Y0115).