What question did this study set out to answer?

This study aims to develop a novel platform for targeted protein degradation using macropinocytosis to enhance the degradation of extracellular proteins.

June 19, 2026ACS Nano

Engineered Lysosome-Targeted Protein Degradation via Hijacking Macropinocytosis

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Authors

WXWen Xu HPHenggong Pan YHYalan Han

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Overview

Randomized trial demonstrates effective protein degradation in various cell types, suggesting new solutions for protein-related diseases.

Key Points

This study aims to develop a novel platform for targeted protein degradation using macropinocytosis to enhance the degradation of extracellular proteins.
Introduced Macropinocytosis-Targeting Chimeras (MapTACs) using a dextran scaffold conjugated with protein-binding aptamers or antibodies.
Evaluated degradation efficacy on monocyte chemotactic protein-1 (MCP-1) in a dose-, time-, and macropinocytosis-dependent manner.
Tested TNF-α-targeting MapTACs in an LPS-induced acute inflammation model in vivo.
MapTACs effectively degrade MCP-1 in a time- and dose-dependent manner with broad applicability to various cell types.
In vivo, TNF-α-targeting MapTACs reduced TNF-α levels with a half-life of approximately 0.72 hours, primarily accumulating in the liver and lung.
Attenuated lung injury in an LPS-induced acute inflammation model was observed with MapTAC application.

Cite This Study

Xu et al. (2026) studied this question.

synapsesocial.com/papers/6a34dd8765a5b0777af2d40a https://doi.org/10.1021/acsnano.6c07737

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June 19, 2026ACS Nano

Engineered Lysosome-Targeted Protein Degradation via Hijacking Macropinocytosis

View Full Paper

Ask AI

Bookmark

Authors

WXWen Xu HPHenggong Pan YHYalan Han

Discussion

Member takes

Overview

Randomized trial demonstrates effective protein degradation in various cell types, suggesting new solutions for protein-related diseases.

Key Points

This study aims to develop a novel platform for targeted protein degradation using macropinocytosis to enhance the degradation of extracellular proteins.
Introduced Macropinocytosis-Targeting Chimeras (MapTACs) using a dextran scaffold conjugated with protein-binding aptamers or antibodies.
Evaluated degradation efficacy on monocyte chemotactic protein-1 (MCP-1) in a dose-, time-, and macropinocytosis-dependent manner.
Tested TNF-α-targeting MapTACs in an LPS-induced acute inflammation model in vivo.
MapTACs effectively degrade MCP-1 in a time- and dose-dependent manner with broad applicability to various cell types.
In vivo, TNF-α-targeting MapTACs reduced TNF-α levels with a half-life of approximately 0.72 hours, primarily accumulating in the liver and lung.
Attenuated lung injury in an LPS-induced acute inflammation model was observed with MapTAC application.

Cite This Study

Xu et al. (2026) studied this question.

synapsesocial.com/papers/6a34dd8765a5b0777af2d40a https://doi.org/10.1021/acsnano.6c07737

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