Condensate corona–nanoparticle complexes transfer functional biomolecules between cells

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.

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Publication Details

Journal
Nature Materials
Published
2026-04-16
DOI
https://doi.org/10.1038/s41563-026-02534-5
Primary Topic
Nanoparticle-Based Drug Delivery
Type
article
Field-Weighted Citation Impact
0.00

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article

Condensate corona–nanoparticle complexes transfer functional biomolecules between cells

Aisling Fleming, Silvia Vercellino, Lorenzo Cursi, Laurent Adumeau et al.
Nature Materials
Nanoparticle-Based Drug Delivery
article

Condensate corona–nanoparticle complexes transfer functional biomolecules between cells

Aisling Fleming, Silvia Vercellino, Lorenzo Cursi, Laurent Adumeau, Marta Saccomanno, Kenneth A. Dawson, David Garry, E. Sheridan, Mura M. McCafferty, Ester Canepa, Zixu Zhao, Vanya Petseva, Filippo Bertoli, Yanqiu Ye, Koen Evers, Kai Liu, Zengchun Xie, Yan Yan, Wei Zhang, Ying Ling Dee, Cara Gaffney, Liufang Liao, Qiwei Wang, Linlin Song, Andrea Marcantognini, Guohui Huang, Yingxin Li, Yuchen Lin, Xia Xiao, Ingrid Morera
article en

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.

Nature Materials
University College Dublin (IE)
European Commission, Science Foundation Ireland, University College Dublin, National Natural Science Foundation of China, Irish Research Council, HORIZON EUROPE Framework Programme, European Regional Development Fund, Interreg
Openalex Percentile: Top 20%
Nanoparticle-Based Drug Delivery
DOIOpen Access PDFOpenAlex
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