Clinical insight-driven micron-sized cholesterol oxidation platform for membrane lipid therapy of advanced ovarian cancer
- Weidong Fei 1, Yu Xin 1, Wenqiang Qian 1, Mingqi Liu 1, Caihong Zheng 1, Yunxi Liu 1, Danfei Chen 2, Ying Zhou 3, Shanshan Xu 1, Xiaodong Wu 4, Mengdan Zhao 5
- Weidong Fei 1, Yu Xin 1, Wenqiang Qian 1
- 1Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
- 2Department of Pediatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310006, China.
- 3Department of Clinical Pharmacology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, 310003, China.
- 4Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. wuxiaodong@zju.edu.cn.
- 5Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. dreamdan@zju.edu.cn.
- 0Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
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View abstract on PubMed
Summary
This summary is machine-generated.This study introduces a novel cholesterol oxidation therapy using PLGA microspheres to treat drug-resistant ovarian cancer. The treatment enhanced chemosensitivity and reduced tumor progression with fewer side effects.
Area Of Science
- Oncology
- Biomedical Engineering
- Nanotechnology
Background
- Ovarian cancer is often diagnosed at advanced stages with drug resistance, limiting survival rates.
- Cholesterol levels correlate with ovarian cancer progression, suggesting targeting cell membranes is a viable therapeutic strategy.
Purpose Of The Study
- To develop and evaluate a novel cholesterol oxidation-mediated membrane lipid therapy for drug-resistant advanced ovarian cancer.
- To investigate the efficacy of PLGA microspheres co-loaded with miriplatin and cholesterol oxidase in vitro and in vivo.
Main Methods
- PLGA microspheres co-encapsulating miriplatin (MiR) and cholesterol oxidase (COD) were prepared and characterized.
- In vitro studies assessed cholesterol oxidation effects on cell membrane properties, mitochondrial function, and chemosensitivity in SKOV3-TR cells.
- In vivo studies evaluated the therapeutic efficacy and safety of the formulation in a drug-resistant metastatic ovarian cancer model.
Main Results
- COD-induced cholesterol oxidation altered membrane rigidity/fluidity, reduced tumor cell migration, and disrupted mitochondrial function.
- The therapy enhanced chemosensitivity by reducing drug resistance proteins and induced apoptosis in resistant cells.
- In vivo studies showed significant reduction in metastasis, tumor destruction, prolonged survival, and decreased chemotherapy side effects.
Conclusions
- Cholesterol oxidation-mediated membrane lipid therapy using PLGA microspheres is a promising strategy for treating advanced, drug-resistant ovarian cancer.
- This approach offers a potential way to overcome platinum resistance and reduce treatment toxicity.
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