Nanoparticle-Protein Interactions in Biomedical Systems

When nanoparticles enter a biological milieu they are rapidly cloaked by a layer of plasma and interstitial proteins, collectively termed the protein corona. This dynamic interface endows nanoparticles with a new biological identity that governs their circulation, cellular uptake, biodistribution and immunogenic profile. The composition and structure of the corona are influenced by nanoparticle size, surface charge, hydrophilicity and the nature of any surface ligands or coatings. In turn, these parameters dictate the kinetics of adsorption and desorption, leading to a distinction between a tightly bound “hard” corona and a more loosely associated “soft” corona. Understanding the factors that govern corona formation is essential for predicting nanoparticle fate in vivo and for rational design of nanocarriers that evade rapid clearance, selectively target diseased tissues and minimise off-target toxicity. Advances in analytical methods now enable in situ characterisation of corona composition and morphology, while computational models are shedding light on the temporal evolution of the protein layer. Insights gained from these studies are driving the development of next-generation nanomedicines for imaging, drug delivery and immunomodulation, with global implications for personalised therapies and diagnostic platforms.

Research from Nature Portfolio

Recent work has demonstrated that glycosylated polyhydroxy polymer modifications on nanovesicles can be fine-tuned to suppress adsorption of immunoglobulins, prolonging systemic circulation and reducing clearance by the liver. By adjusting the ratio of amino to hydroxyl groups on the vesicle surface, this approach selectively enriches tumour-distinctive proteins in the corona and enhances uptake by malignant cells, yielding superior antitumour efficacy compared with conventional PEGylated liposomes. Complementing this, foundational studies on polymeric nanoparticles have revealed that a critical density of poly(ethylene glycol) chains on the nanoparticle surface minimises non-specific protein binding, independent of particle size, and prolongs circulation. These investigations have further shown that adsorption of specific apolipoproteins can extend half-life in the bloodstream and that complement activation does not fully account for clearance, highlighting roles for lipoprotein receptors in nanoparticle pharmacokinetics.

Nanoparticle-Protein Interactions in Biomedical Systems publication trend

The graph below shows the total number of articles in nanoparticle-protein interactions in biomedical systems across all publications each year (not limited to Nature Index journals).

Technical terms

Protein corona: The layer of proteins and biomolecules that spontaneously adsorbs onto nanoparticles upon exposure to biological fluids, defining their biological identity.

Hard corona: The subset of the protein corona composed of tightly bound proteins with low exchange rates and long residence times on the nanoparticle surface.

Soft corona: The outer region of the protein corona consisting of loosely associated proteins in rapid dynamic exchange with the surrounding medium.

PEGylation: The modification of nanoparticle surfaces with poly(ethylene glycol) chains to resist protein adsorption, reduce immunogenicity and prolong circulation.

Nanovesicle: A lipid-based nanoscale carrier engineered to encapsulate and deliver therapeutic agents with controlled release and targeting capabilities.

References

1. In situ characterization techniques of protein corona around nanomaterials. Chemical Society Reviews (2024).
2. Local Environments Created by the Ligand Coating of Nanoparticles and Their Implications for Sensing and Surface Reactions. Accounts of Chemical Research (2023).
3. Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery. Nature Communications (2024).
4. Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nature Communications (2017).
5. Complementary analysis of the hard and soft protein corona: sample preparation critically effects corona composition. Nanoscale (2015).
6. Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid. PLOS ONE (2010).