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

by Selleckchem | Jun 17 2023

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.

Comments:

The study focuses on addressing the challenge of treating carboplatin-resistant ovarian cancer, which has high mortality rates. The researchers designed and prepared a targeted drug delivery system using hyaluronic acid-decorated metal-organic frameworks (HA@MOF) to deliver a specific inhibitor called GSK-J1, which targets the JMJD3 demethylase enzyme. This drug delivery system is referred to as HA@MOF@GSK-J1.

The researchers evaluated the effectiveness of HA@MOF@GSK-J1 in inhibiting ovarian cancer cells in laboratory experiments (in vitro). The results showed that the treatment was highly effective in inhibiting ovarian cancer cell growth.

Additionally, HA@MOF@GSK-J1 was found to induce apoptosis (programmed cell death), reduce cell motility, and decrease the formation of cell spheroids. These effects were attributed to the attenuation of HER2 activity through the activation of H3K27 methylation in the promoter region of the HER2 gene.

Furthermore, the researchers conducted in vivo experiments using carboplatin-resistant ovarian tumor xenografts (implanted tumors in mice). The results of these experiments confirmed that HA@MOF@GSK-J1 had superior treatment efficacy compared to other treatments for carboplatin-resistant ovarian cancer.

Overall, the study highlights the potential of HA@MOF@GSK-J1 as an effective strategy for improving the treatment of carboplatin-resistant ovarian cancer. The targeted drug delivery system using hyaluronic acid-decorated metal-organic frameworks, combined with the specific JMJD3 demethylase inhibitor GSK-J1, demonstrated promising results in inhibiting ovarian cancer cells, inducing apoptosis, and reducing tumor growth in animal models. These findings suggest that HA@MOF@GSK-J1 could be a valuable approach in overcoming chemoresistance and improving outcomes in patients with carboplatin-resistant ovarian cancer.