Abstract |
Multidrug resistance remains a great challenge for cancer chemotherapy. Herein, a biomimetic drug delivery system based on lemon-derived extracellular vesicles (EVs) nanodrugs (marked with heparin-cRGD-EVs- doxorubicin (HRED)) is demonstrated, achieving highly efficient overcoming cancer multidrug resistance. The HRED is fabricated by modifying functional heparin-cRGD (HR) onto the surface of EVs and then by loading with doxorubicin (DOX). The obtained HRED enable to effectively enter DOX-resistant cancer cells by caveolin-mediated endocytosis (main), macropinocytosis (secondary), and clathrin-mediated endocytosis (last), exhibiting excellent cellular uptake capacity. The diversified endocytosis capacity of HRED can efficiently dissipate intracellular energy and meanwhile trigger downstream production reduction of adenosine triphosphate ( ATP), leading to a significant reduction of drug efflux. Consequently, they show excellent anti-proliferation capacities to DOX-resistant ovarian cancer, ensuring the efficiently overcoming ovarian cancer multidrug resistance in vivo. The authors believe this strategy provides a new strategy by endocytosis triggered-energy dissipation and ATP production reduction to design drug delivery system for overcoming cancer multidrug resistance.
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Authors | Qian Xiao, Wei Zhao, Chentian Wu, Xuejiao Wang, Jianping Chen, Xiubo Shi, Suinan Sha, Jinheng Li, Xiaomei Liang, Yulu Yang, Haoyan Guo, Ying Wang, Jun-Bing Fan |
Journal | Advanced science (Weinheim, Baden-Wurttemberg, Germany)
(Adv Sci (Weinh))
Vol. 9
Issue 20
Pg. e2105274
(07 2022)
ISSN: 2198-3844 [Electronic] Germany |
PMID | 35187842
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH. |
Chemical References |
- Doxorubicin
- Adenosine Triphosphate
- Heparin
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Topics |
- Adenosine Triphosphate
(pharmacology)
- Doxorubicin
(pharmacology, therapeutic use)
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Endocytosis
- Extracellular Vesicles
- Female
- Heparin
(pharmacology)
- Humans
- Nanoparticles
(therapeutic use)
- Ovarian Neoplasms
(drug therapy)
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