Selective Intracellular Delivery of Antibodies in Cancer Cells with Nanocarriers Sensing Endo/Lysosomal Enzymatic Activity

Abstract: The differential enzymatic activity in the endo/lysosomes of particular cells could trigger targeted endosomal escape functions, enabling selective intracellular protein delivery. However, this strategy may be jeopardized due to protein degradation during endosomal trafficking. Herein, using custom made fluorescent probes to assess the endosomal activity of cathepsin B (CTSB) and protein degradation, we found that certain cancer cells with hyperacidified endosomes grant a spatiotemporal window where CTSB activity surpass protein digestion. This inspired the engineering of antibody‐loaded polymeric nanocarriers having CTSB‐activatable endosomal escape ability. The nanocarriers selectively escaped from the endo/lysosomes in the cells with high endosomal CTSB activity and delivered active antibodies to intracellular targets. This study provides a viable strategy for cell‐specific protein delivery using stimuli‐responsive nanocarriers with controlled endosomal escape.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Selective Intracellular Delivery of Antibodies in Cancer Cells with Nanocarriers Sensing Endo/Lysosomal Enzymatic Activity ; day:27 ; month:02 ; year:2024 ; extent:9
Angewandte Chemie / International edition. International edition ; (27.02.2024) (gesamt 9)

Urheber
Chen, Pengwen
Yang, Wenqian
Mochida, Yuki
Li, Shangwei
Hong, Taehun
Kinoh, Hiroaki
Kataoka, Kazunori
Cabral, Horacio

DOI
10.1002/anie.202317817
URN
urn:nbn:de:101:1-2024022714250979465699
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:58 MESZ

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Beteiligte

  • Chen, Pengwen
  • Yang, Wenqian
  • Mochida, Yuki
  • Li, Shangwei
  • Hong, Taehun
  • Kinoh, Hiroaki
  • Kataoka, Kazunori
  • Cabral, Horacio

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