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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 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.
AuthorsQian 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
JournalAdvanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 9 Issue 20 Pg. e2105274 (07 2022) ISSN: 2198-3844 [Electronic] Germany
PMID35187842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
Chemical References
  • Doxorubicin
  • Adenosine Triphosphate
  • Heparin
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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