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

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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.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: 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)

Creator: 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

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 14.08.2025, 10:58 AM CEST

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

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

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Other Objects (12)

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

Uptake mechanism, intracellular trafficking and endo-lysosomal pH monitoring of polystyrene nanoparticles

Nanomechanical action opens endo-lysosomal compartments

Autophagic and endo-lysosomal dysfunction in neurodegenerative disease

Inhibition of endo-lysosomal function exacerbates vascular calcification

Pathways of integrins in the endo-lysosomal system

Pseudobacterial nanocarriers for intracellular delivery of anti-infectives

Enhanced enzymatic production of cholesteryl 6ʹ-acylglucoside impairs lysosomal degradation for the intracellular survival of Helicobacter pylori

Correction to: Pathways of integrins in the endo-lysosomal system

Bioresponsive nanocarriers for targeted intracellular delivery of proteins and peptides

Presenilin deficiency leads to altered protein N-glycosylation and endo-lysosomal cholesterol accumulation

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

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

Uptake mechanism, intracellular trafficking and endo-lysosomal pH monitoring of polystyrene nanoparticles

Nanomechanical action opens endo-lysosomal compartments

Autophagic and endo-lysosomal dysfunction in neurodegenerative disease

Inhibition of endo-lysosomal function exacerbates vascular calcification

Pathways of integrins in the endo-lysosomal system

Pseudobacterial nanocarriers for intracellular delivery of anti-infectives

Enhanced enzymatic production of cholesteryl 6ʹ-acylglucoside impairs lysosomal degradation for the intracellular survival of Helicobacter pylori

Correction to: Pathways of integrins in the endo-lysosomal system

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RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

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

Uptake mechanism, intracellular trafficking and endo-lysosomal pH monitoring of polystyrene nanoparticles

Nanomechanical action opens endo-lysosomal compartments

Autophagic and endo-lysosomal dysfunction in neurodegenerative disease

Inhibition of endo-lysosomal function exacerbates vascular calcification

Pathways of integrins in the endo-lysosomal system

Pseudobacterial nanocarriers for intracellular delivery of anti-infectives

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Presenilin deficiency leads to altered protein N-glycosylation and endo-lysosomal cholesterol accumulation

RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

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