GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer

Bing Yang; Wenxu Liu; Meiying Li; Jingxin Mo

doi:10.3389/fphar.2022.1023719

GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer

Front Pharmacol. 2022 Nov 7:13:1023719. doi: 10.3389/fphar.2022.1023719. eCollection 2022.

Authors

Bing Yang¹, Wenxu Liu², Meiying Li², Jingxin Mo^{3

4}

Affiliations

¹ Department of Gynecology, The Affiliated Hospital of Guilin Medical University, Guilin, China.
² School of Pharmacy, Guilin Medical University, Guilin, China.
³ Lab of Neurology, The Affiliated Hospital of Guilin Medical University, Guilin, China.
⁴ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia.

Abstract

Despite intensive research, ovarian cancer has the highest mortality rates among gynecological malignancies, partly because of its rapid acquisition of chemoresistance to platinum therapy. Hence, strategies are needed to effectively treat carboplatin-resistant ovarian cancer. In this study, we designed and prepared hyaluronic acid-decorated metal-organic frameworks for the targeted delivery of GSK-J1, a JMJD3 demethylase inhibitor (HA@MOF@GSK-J1) for the synergistic treatment of carboplatin-resistant ovarian cancer. HA@MOF@GSK-J1 showed outstanding effectiveness in the inhibition of ovarian cancer in vitro. Furthermore, HA@MOF@GSK-J1 demonstrated higher induction of apoptosis, reduced cell motility, and diminished cell spheroids by attenuating HER2 activity through the effectual activation of H3K27 methylation in its promoter area. Finally, our in vivo results confirmed that HA@MOF@GSK-J1 had better treatment efficacy for carboplatin-resistant ovarian tumor xenografts. Our results highlight the potential of HA@MOF@GSK-J1 as an effective strategy to improve the treatment of carboplatin-resistant ovarian cancer.

Keywords: HER2; MOF; epigenetic modification; hyaluronic acid; ovarian cancer.