Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction
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 mul...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-07-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202105274 |
| _version_ | 1828747428049715200 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Qian Xiao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T04:41:38Z |
| format | Article |
| id | doaj.art-4027d2766314488aa82900050ae50be9 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-14T04:41:38Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-4027d2766314488aa82900050ae50be92022-12-22T02:11:38ZengWileyAdvanced Science2198-38442022-07-01920n/an/a10.1002/advs.202105274Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production ReductionQian Xiao0Wei Zhao1Chentian Wu2Xuejiao Wang3Jianping Chen4Xiubo Shi5Suinan Sha6Jinheng Li7Xiaomei Liang8Yulu Yang9Haoyan Guo10Ying Wang11Jun‐Bing Fan12Cancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaDivision of Vascular and Interventional Radiology Department of General Surgery, Nanfang Hospital Southern Medical University Guangzhou Guangdong 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaCancer Research Institute Experimental Education/Administration Center School of Basic Medical Sciences Southern Medical University Guangzhou 510515 P. R. ChinaAbstract 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.https://doi.org/10.1002/advs.202105274biomimetic nanodrugsendocytosisenergy dissipationlemon‐derived extracellular vesiclesmultidrug resistance |
| spellingShingle | 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 Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction Advanced Science biomimetic nanodrugs endocytosis energy dissipation lemon‐derived extracellular vesicles multidrug resistance |
| title | Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction |
| title_full | Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction |
| title_fullStr | Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction |
| title_full_unstemmed | Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction |
| title_short | Lemon‐Derived Extracellular Vesicles Nanodrugs Enable to Efficiently Overcome Cancer Multidrug Resistance by Endocytosis‐Triggered Energy Dissipation and Energy Production Reduction |
| title_sort | lemon derived extracellular vesicles nanodrugs enable to efficiently overcome cancer multidrug resistance by endocytosis triggered energy dissipation and energy production reduction |
| topic | biomimetic nanodrugs endocytosis energy dissipation lemon‐derived extracellular vesicles multidrug resistance |
| url | https://doi.org/10.1002/advs.202105274 |
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