CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma
Abstract: BRD4 is a member of the BET protein family involved in chromatin remodeling and transcriptional regulation. Several BET inhibitors (BETi) have entered clinical trials, demonstrating potential in inducing cancer cell apoptosis and tumor regression. However, resistance to BETi is common in solid tumors. In pancreatic cancer, it is found that cancer‐associated fibroblasts (CAFs) in the tumor microenvironment reduce the BET inhibitor JQ1 sensitivity by inducing BRD4 expression. Moreover, CAFs play a crucial role in the formation of a dense stromal barrier. Therefore, targeting CAFs in the tumor microenvironment of pancreatic cancer not only enhances cancer cells sensitivity to JQ1 but also increases drug perfusion and improves oxygen supply, thus reducing glycolysis and limiting energy supply. To address this challenge, a homologous targeting mechanism utilizing activated fibroblast membrane‐coated liposomes is proposed for specific drug precise target to CAFs‐rich pancreatic cancer. Additionally, TAT peptides enable liposomes penetration, delivering PFD for targeted anti‐fibrotic therapy, reducing extracellular matrix generation and glycolysis, and enhancing JQ1 delivery and sensitivity. In conclusion, the findings indicate the tremendous potential of this CAFs‐targeting liposomal delivery system in pancreatic cancer.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma ; day:15 ; month:11 ; year:2023 ; extent:17
Advanced science ; (15.11.2023) (gesamt 17)
- Creator
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Zhang, Yin
Yu, Ranran
Zhao, Cheng
Liang, Jiawei
Zhang, Yixuan
Su, Haochen
Zhao, Jing
Wu, Hao
Xu, Shijin
Zhang, Ziying
Wang, Lei
Zou, Xiaoping
Zhu, Yun
Zhang, Shu
Lv, Ying
- DOI
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10.1002/advs.202305279
- URN
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urn:nbn:de:101:1-2023111614233523089128
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:20 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Zhang, Yin
- Yu, Ranran
- Zhao, Cheng
- Liang, Jiawei
- Zhang, Yixuan
- Su, Haochen
- Zhao, Jing
- Wu, Hao
- Xu, Shijin
- Zhang, Ziying
- Wang, Lei
- Zou, Xiaoping
- Zhu, Yun
- Zhang, Shu
- Lv, Ying
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