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Tumour-derived small extracellular vesicles act as a barrier to therapeutic nanoparticle delivery.
Gong, Ningqiang; Zhong, Wenqun; Alameh, Mohamad-Gabriel; Han, Xuexiang; Xue, Lulu; El-Mayta, Rakan; Zhao, Gan; Vaughan, Andrew E; Qin, Zhiyuan; Xu, Fengyuan; Hamilton, Alex G; Kim, Dongyoon; Xu, Junchao; Kim, Junhyong; Teng, Xucong; Li, Jinghong; Liang, Xing-Jie; Weissman, Drew; Guo, Wei; Mitchell, Michael J.
Afiliación
  • Gong N; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Zhong W; Division of Life Sciences and Medicine, Center for BioAnalytical Chemistry, Hefei National Research Center for Physical Science at the Microscale, University of Science and Technology of China, Hefei, China.
  • Alameh MG; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
  • Han X; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Xue L; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • El-Mayta R; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Zhao G; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Vaughan AE; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Qin Z; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Xu F; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
  • Hamilton AG; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
  • Kim D; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Xu J; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Kim J; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Teng X; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA.
  • Li J; Department of Chemistry, Tsinghua University, Beijing, China.
  • Liang XJ; Department of Chemistry, Tsinghua University, Beijing, China.
  • Weissman D; Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.
  • Guo W; Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. dreww@upenn.edu.
  • Mitchell MJ; Penn institute for RNA innovation, University of Pennsylvania, Philadelphia, PA, USA. dreww@upenn.edu.
Nat Mater ; 2024 Sep 02.
Article en En | MEDLINE | ID: mdl-39223270
ABSTRACT
Nanoparticles are promising for drug delivery applications, with several clinically approved products. However, attaining high nanoparticle accumulation in solid tumours remains challenging. Here we show that tumour cell-derived small extracellular vesicles (sEVs) block nanoparticle delivery to tumours, unveiling another barrier to nanoparticle-based tumour therapy. Tumour cells secrete large amounts of sEVs in the tumour microenvironment, which then bind to nanoparticles entering tumour tissue and traffic them to liver Kupffer cells for degradation. Knockdown of Rab27a, a gene that controls sEV secretion, decreases sEV levels and improves nanoparticle accumulation in tumour tissue. The therapeutic efficacy of messenger RNAs encoding tumour suppressing and proinflammatory proteins is greatly improved when co-encapsulated with Rab27a small interfering RNA in lipid nanoparticles. Together, our results demonstrate that tumour cell-derived sEVs act as a defence system against nanoparticle tumour delivery and that this system may be a potential target for improving nanoparticle-based tumour therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nat Mater Asunto de la revista: CIENCIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nat Mater Asunto de la revista: CIENCIA / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido