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Precision Oligo(ethylene glycol) Interfaces Shape Nanoparticle Biodistribution through In Vivo Protein Corona
Mingxuan Hou1, Minglong Chen1, Jie Cen1
1State Key Laboratory of Precision and Intelligent Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
Journal of the American Chemical Society
|June 18, 2026
Summary
A limited set of key proteins in nanoparticle coronas can predict organ distribution in vivo. This finding helps explain how nanoparticle surface chemistry and disease influence where nanoparticles go in the body.
Area of Science:
- Nanomedicine
- Biomaterials Science
- Proteomics
Background:
- Nanoparticle surface chemistry influences biological interactions and in vivo fate.
- Protein corona formation is a key mediator of nanoparticle-host interactions, but specific component roles in biodistribution are unclear.
- Existing methods for in vivo corona analysis are confounded by factors like PEG dispersity.
Purpose of the Study:
- To establish a framework linking nanoparticle corona composition to organ-level biodistribution.
- To investigate the influence of specific corona proteins on nanoparticle uptake patterns.
- To understand how nanoparticle fate is affected by both interface chemistry and pathological conditions.
Main Methods:
- Chemically uniform nanoparticle interfaces were created using precision oligo(ethylene glycol) ligands.
- Co-doped Fe3O4 nanoparticles and magnetic-assisted sorting were used for improved in vivo corona recovery and analysis.
- An integrated approach combining pathological models, quantitative proteomics, reconstructed coronas, genetic ablation, and pharmacological inhibition was employed.
Main Results:
- A simplified four-protein corona (ApoE, ApoA-I, C3, C1qA) partly explained organ-associated nanoparticle uptake.
- Corona signatures correlated with in vivo organ-level biodistribution.
- These signatures helped explain shifts in nanoparticle distribution under pathological conditions.
Conclusions:
- A limited set of key corona proteins, rather than overall corona complexity, can predict nanoparticle organ distribution.
- The findings support a corona-based framework for understanding nanoparticle behavior in vivo.
- This framework links nanoparticle interface chemistry and biological state to organ distribution under both physiological and pathological conditions.
