Condensate corona–nanoparticle complexes transfer functional biomolecules between cells

Abstract Biological nanoscale assemblies transfer proteins and RNAs between cells and cellular compartments. Nonetheless, it is unclear if exogenous and synthetic nanostructures affect these molecular assemblies and processes. Here we report nanostructure–biological hybrid complexes that are formed by synthetic nanoparticles after being internalized by cells. These nanoparticles, in rare events, acquire an overlaid cell-derived biomolecular condensate corona, afterwards being exported to the extracellular space to be internalized by other cells. The condensate corona is compositionally distinct from extracellular vesicles, containing intact proteins, mRNAs and long RNAs. The condensate corona is mechanically robust in extracellular conditions, becoming fluid within endosomes, where it detaches from the particle core and escapes the endo-lysosomal pathway, redistributing its protein and RNA components to cytosolic and nuclear compartments. Grafting short peptides onto the surface of purified corona–nanoparticle complexes prevents detachment and endo-lysosomal escape, suggesting that recognition interactions at the condensate–endosome lumen interface control intracellular access. Overall, these findings reveal a natural, condensate-mediated route for the transfer of biomolecular machinery including RNA between cells, which could inspire design principles for future delivery systems.