Engineered Patelets as Targeted Protein Degraders and Application to Breast Cancer Models

This study develops a method to engineer platelets

for the degradation of either intracellular or

extracellular proteins of interest (POIs) in vivo by

covalently labeling heat shock protein 90 (HSP90)

in platelets with a POI ligand to build the degrader

platelets (DePLTs). DePLTs target wound areas and

undergo activation. Once activated, DePLTs initiate

two protein degradation mechanisms: First, the

labeled HSP90 enters target cells through membrane

fusion, using the ubiquitin-proteasome system (UPS)

to degrade intracellular POIs. Second, the free HSP90

released by DePLTs guides extracellular POIs to the

lysosome for lysosome-mediated protein degradation. 

The platelet-templated strategy overcomes the

limitations of the commonly used chimeras, advancing

in vivo applications of targeted protein degradation.