GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer
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 desig...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1023719/full |
| _version_ | 1797984374887546880 |
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| author | Bing Yang Wenxu Liu Meiying Li Jingxin Mo Jingxin Mo |
| author_facet | Bing Yang Wenxu Liu Meiying Li Jingxin Mo Jingxin Mo |
| author_sort | Bing Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T07:01:44Z |
| format | Article |
| id | doaj.art-ea311bba28b04fd8b62339715c8ed641 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T07:01:44Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ea311bba28b04fd8b62339715c8ed6412022-12-22T04:38:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10237191023719GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancerBing Yang0Wenxu Liu1Meiying Li2Jingxin Mo3Jingxin Mo4Department of Gynecology, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaSchool of Pharmacy, Guilin Medical University, Guilin, ChinaSchool of Pharmacy, Guilin Medical University, Guilin, ChinaLab of Neurology, The Affiliated Hospital of Guilin Medical University, Guilin, ChinaGraduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, AustraliaDespite 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.1023719/fullovarian cancerhyaluronic acidMOFHER2epigenetic modification |
| spellingShingle | Bing Yang Wenxu Liu Meiying Li Jingxin Mo Jingxin Mo GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer Frontiers in Pharmacology ovarian cancer hyaluronic acid MOF HER2 epigenetic modification |
| title | GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer |
| title_full | GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer |
| title_fullStr | GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer |
| title_full_unstemmed | GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer |
| title_short | GSK-J1-loaded, hyaluronic acid-decorated metal-organic frameworks for the treatment of ovarian cancer |
| title_sort | gsk j1 loaded hyaluronic acid decorated metal organic frameworks for the treatment of ovarian cancer |
| topic | ovarian cancer hyaluronic acid MOF HER2 epigenetic modification |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1023719/full |
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