Protein corona: a new approach for nanomedicine design

Abstract

After administration of nanoparticle (NP) into biological fluids, an NP-protein complex is formed, which represents the "true identity" of NP in our body. Hence, protein-NP interaction should be carefully investigated to predict and control the fate of NPs or drug-loaded NPs, including systemic circulation, biodistribution, and bioavailability. In this review, we mainly focus on the formation of protein corona and its potential applications in pharmaceutical sciences such as prediction modeling based on NP-adsorbed proteins, usage of active proteins for modifying NP to achieve toxicity reduction, circulation time enhancement, and targeting effect. Validated correlative models for NP biological responses mainly based on protein corona fingerprints of NPs are more highly accurate than the models solely set up from NP properties. Based on these models, effectiveness as well as the toxicity of NPs can be predicted without in vivo tests, while novel cell receptors could be identified from prominent proteins which play important key roles in the models. The ungoverned protein adsorption onto NPs may have generally negative effects such as rapid clearance from the bloodstream, hindrance of targeting capacity, and induction of toxicity. In contrast, controlling protein adsorption by modifying NPs with diverse functional proteins or tailoring appropriate NPs which favor selective endogenous peptides and proteins will bring promising therapeutic benefits in drug delivery and targeted cancer treatment.

Keywords: exchange of adsorbed protein; predictive modeling; protein corona; protein-nanoparticle interaction; targeting drug delivery; toxicity reduction.

Figure 1

The formation of protein corona and exchange of adsorbed proteins over time in biological conditions. Notes: (A) Immediately upon exposure. (B) After a longer exposure time, with displacement of proteins among the hard corona, soft corona, and cellular environment. (C) Major factors affecting protein corona pattern divided into two categorized properties: nanoparticle and environment. Abbreviation: NP, nanoparticle.

Figure 2

A scheme for the establishment of predictive model. Note: From the model, biological responses can be predicted without further experiments, and highly expressed receptors can be identified from the most influencing proteins, providing data for NP design. Abbreviation: NP, nanoparticle.

Figure 3

New targeting strategy for NP design to cells using different surface-modified ligands. Notes: Left: Adsorbed proteins hinder targeting ligands conjugated on the NP surface. Right: Surface-modified NPs favor functional proteins, which direct NPs to the desired cell. Abbreviation: NP, nanoparticle.