A nature-inspired nanoplatform for multi-protein targeted degradation via the autophagy-lysosome pathway

Apr 3, 2026Cell chemical biology

A nature-inspired nanoparticle system for breaking down multiple proteins using the cell's recycling pathway

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Abstract

Extracellular vesicles (EVs) are predominantly degraded via the lysosomal pathway.

  • MAP1LC3B recognizes SNX18 on endosome-escaped EVs to facilitate their sorting into the autolysosomal pathway.
  • Surface display of LIR motifs optimized lysosomal sorting efficiency of EVs.
  • An EV-based targeted protein degradation nanoplatform was constructed that is modular and can integrate with monoclonal antibodies.
  • The nanoplatform demonstrated efficiency and selectivity in degrading proteins such as EGFR, PD-L1, and VEGF.
  • It also exhibited multi-targeting capability by simultaneously degrading both EGFR and VEGF.

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