Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition
Abstract The dysregulated cholesterol metabolism in breast cancer cells drives malignancy, invasion, and metastasis, emphasizing the significance of reducing abnormal cholesterol accumulation for effective cancer treatment and metastasis inhibition. Despite its promise, cholesterol oxidase (ChOx) en...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409967 |
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| author | Shuangqian Yan Panpan Xue Ying Sun Tingjie Bai Sijie Shao Xuemei Zeng |
| author_facet | Shuangqian Yan Panpan Xue Ying Sun Tingjie Bai Sijie Shao Xuemei Zeng |
| author_sort | Shuangqian Yan |
| collection | DOAJ |
| description | Abstract The dysregulated cholesterol metabolism in breast cancer cells drives malignancy, invasion, and metastasis, emphasizing the significance of reducing abnormal cholesterol accumulation for effective cancer treatment and metastasis inhibition. Despite its promise, cholesterol oxidase (ChOx) encounters challenge due to limited catalytic efficiency and susceptibility to harsh conditions. To overcome these hurdles, biocompatible nanoplatforms (Cu‐HPB/C) tailored for efficient cholesterol depletion are introduced. Cu2+‐doped hollow Prussian blue (Cu‐HPB) acts as a carrier, shelter, and enhancer for ChOx, bolstering tumor‐targeting ability, stability, and enzymatic activity. Tumor‐responsive released Cu2+ notably augments ChOx activity, facilitating cholesterol depletion and disrupting lipid rafts, thereby impeding cell invasion and migration. Additionally, H2O2 generated from the oxidase reaction enhances Cu‐HPB's chemo dynamic therapeutic efficacy. Transcriptomic analysis validates Cu‐HPB/C's impact on cholesterol homeostasis and reveals cell death mechanisms including oxidative stress, ferroptosis, cuproptosis, and apoptosis. Demonstrating therapeutic efficacy in both 4T1 tumor subcutaneous and metastasis mouse models, the study presents a direct and effective strategy for tumor therapy and metastasis inhibition through enhanced cholesterol depletion. |
| format | Article |
| id | doaj-art-af56c17880d7416892a360492b8feaba |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-af56c17880d7416892a360492b8feaba2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202409967Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis InhibitionShuangqian Yan0Panpan Xue1Ying Sun2Tingjie Bai3Sijie Shao4Xuemei Zeng5Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University Biomedical Research Center of South China College of Life Sciences Fujian Normal University 1 Keji Road Fuzhou 350117 P. R. ChinaThe Straits Institute of Flexible Electronics (SIFE, Future Technologies) Straits Laboratory of Flexible Electronics (SLoFE) Fujian Normal University Fuzhou Fujian 350117 P. R. ChinaDepartment of Gastroenterology Fuzhou No. 1 Hospital Affiliated with Fujian Medical University Fuzhou Fujian 350009 P. R. ChinaKey Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University Biomedical Research Center of South China College of Life Sciences Fujian Normal University 1 Keji Road Fuzhou 350117 P. R. ChinaThe Straits Institute of Flexible Electronics (SIFE, Future Technologies) Straits Laboratory of Flexible Electronics (SLoFE) Fujian Normal University Fuzhou Fujian 350117 P. R. ChinaKey Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University Biomedical Research Center of South China College of Life Sciences Fujian Normal University 1 Keji Road Fuzhou 350117 P. R. ChinaAbstract The dysregulated cholesterol metabolism in breast cancer cells drives malignancy, invasion, and metastasis, emphasizing the significance of reducing abnormal cholesterol accumulation for effective cancer treatment and metastasis inhibition. Despite its promise, cholesterol oxidase (ChOx) encounters challenge due to limited catalytic efficiency and susceptibility to harsh conditions. To overcome these hurdles, biocompatible nanoplatforms (Cu‐HPB/C) tailored for efficient cholesterol depletion are introduced. Cu2+‐doped hollow Prussian blue (Cu‐HPB) acts as a carrier, shelter, and enhancer for ChOx, bolstering tumor‐targeting ability, stability, and enzymatic activity. Tumor‐responsive released Cu2+ notably augments ChOx activity, facilitating cholesterol depletion and disrupting lipid rafts, thereby impeding cell invasion and migration. Additionally, H2O2 generated from the oxidase reaction enhances Cu‐HPB's chemo dynamic therapeutic efficacy. Transcriptomic analysis validates Cu‐HPB/C's impact on cholesterol homeostasis and reveals cell death mechanisms including oxidative stress, ferroptosis, cuproptosis, and apoptosis. Demonstrating therapeutic efficacy in both 4T1 tumor subcutaneous and metastasis mouse models, the study presents a direct and effective strategy for tumor therapy and metastasis inhibition through enhanced cholesterol depletion.https://doi.org/10.1002/advs.202409967cholesterol metabolism regulationcholesterol oxidasemetal organic frameworkstumor metabolism therapytumor metastasis inhibition |
| spellingShingle | Shuangqian Yan Panpan Xue Ying Sun Tingjie Bai Sijie Shao Xuemei Zeng Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition Advanced Science cholesterol metabolism regulation cholesterol oxidase metal organic frameworks tumor metabolism therapy tumor metastasis inhibition |
| title | Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition |
| title_full | Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition |
| title_fullStr | Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition |
| title_full_unstemmed | Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition |
| title_short | Cupric Doping Hollow Prussian Blue Nanoplatform for Enhanced Cholesterol Depletion: a Promising Strategy for Breast Cancer Therapy and Metastasis Inhibition |
| title_sort | cupric doping hollow prussian blue nanoplatform for enhanced cholesterol depletion a promising strategy for breast cancer therapy and metastasis inhibition |
| topic | cholesterol metabolism regulation cholesterol oxidase metal organic frameworks tumor metabolism therapy tumor metastasis inhibition |
| url | https://doi.org/10.1002/advs.202409967 |
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