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

  • 0Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Angewandte Chemie +

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February 11, 2024

|

February 11, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

This study developed smart nanocarriers that release therapeutic antibodies inside cancer cells. These nanocarriers exploit cancer cells' unique endosomal environment for targeted delivery and avoid protein degradation, enhancing treatment efficacy.

Area Of Science

  • Biomedical Engineering
  • Nanotechnology
  • Cell Biology

Background

  • Intracellular protein delivery faces challenges like premature protein degradation within endosomes.
  • Targeted endosomal escape strategies are hindered by the complex endosomal trafficking pathway.
  • Cancer cells exhibit distinct endosomal characteristics, including hyperacidification.

Purpose Of The Study

  • To engineer stimuli-responsive nanocarriers for selective intracellular protein delivery.
  • To overcome protein degradation during endosomal trafficking.
  • To leverage cancer cell-specific endosomal activity for targeted drug release.

Main Methods

  • Development of custom fluorescent probes to monitor cathepsin B (CTSB) activity and protein degradation.
  • Characterization of endosomal acidification and CTSB activity in cancer cells.
  • Design and synthesis of antibody-loaded polymeric nanocarriers with CTSB-activatable endosomal escape.

Main Results

  • Identified a spatiotemporal window in hyperacidified endosomes where CTSB activity exceeds protein digestion.
  • Demonstrated selective endosomal escape of nanocarriers in cancer cells with high CTSB activity.
  • Confirmed successful delivery of active antibodies to intracellular targets, bypassing degradation.

Conclusions

  • Engineered nanocarriers provide a viable strategy for cell-specific protein delivery.
  • CTSB-activatable endosomal escape mechanism enhances therapeutic efficacy by controlling drug release.
  • Stimuli-responsive nanocarriers offer a promising approach for targeted cancer therapy.

Keywords:

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