Biological Recognition of Biomolecular Corona

Introduction When the nanoparticle surface comes in contact with a biological milieu, adsorption processes may lead to a well-defined surface-assembly of biomolecules derived from the environment. Appropriately presented, and... [ view full abstract ]

Introduction
When the nanoparticle surface comes in contact with a biological milieu, adsorption processes may lead to a well-defined surface-assembly of biomolecules derived from the environment. Appropriately presented, and sufficiently long-lived (‘hard corona’) biomolecular motifs presented at the surface would define how a nanoparticle first interacts with and is recognised by cells. Besides their fundamental importance, such questions likely define many key impacts on efficacy of nanoparticle-based therapies, including their bio-distribution and nanomedicine targeting. For instance, well-defined active processes driven by receptors on the specialized cells of the liver could drive nanoparticle accumulation. However, little is known of the molecular organisation of various proteins in the corona. Hence, the detailed molecular interactions between the presented protein motifs and receptors are yet to be elucidated.
Methods
Here we present a systematic method to advance such hypotheses, by direct investigation of nanoparticle-receptor interactions in biological milieu. Firstly, we have built a cell receptor library by transfection receptor of interest to host cells. This system allows us to examine the dependence of nanoparticle uptake to a given receptor in appropriate biological milieu. In addition, this approach overcomes the limitations that some receptors cannot be isolated in a functionally relevant form, as their expression levels are interdependent in endogenously expressed cells. In parallel, we also have developed tools by using monoclonal antibodies to detect epitope presentation on the nanoparticle surface. Altogether, we have been able to characterise the biomolecular corona with molecular details and their interactions with different receptors.
Results and Discussion
In this presentation, we will illustrate the recognition of biomolecular corona by a couple of key receptors, low-density-lipoprotein receptor (LDLR) and Fc-gamma receptor I (FcγRI), which are abundant in the liver. By using both flow cytometry and microscopy, we have shown that the ‘labelling’ of nanoparticles by biomolecular adsorption processes allows for ubiquitous nanoparticle multi-pathway involvement in biological processes, which governs the liver accumulation of nanoparticles.