How Corona Formation Impacts Nanomaterials as Drug Carriers

Abstract

As drugs/drug carriers, upon encountering physiological fluids, nanoparticles adsorb biological molecules almost immediately to form a biocorona, which is often simply called a corona. Once the corona is formed, it dictates the subsequent fate of the drug nanoparticle as a therapeutic agent. Protein adsorption on micron-size or even bigger particles was originally described by the Vroman effect. It has served as a useful framework to understand the corona formation. Proteins that are irreversibly adsorbed on nanoparticles form what is called a hard corona. Beyond that is the exchangeable population of proteins, which constitute the dynamic structure called a soft corona. More than the abundance, the affinity of the proteins toward the nanoparticles decides which ones end up in the corona. For example, the more common serum albumin, which is deposited initially, is displaced by fibrinogen, which has a higher affinity for gold nanoparticles. The curvature of the particle is a crucial parameter with bigger particles generally able to bind a more diverse population of proteins from the physiological milieu. The earlier perception of the corona formation being a challenge for drug targeting, etc. has been turned into an opportunity by engineering corona to manipulate properties like circulating half-lives, capacity to evade the immune system, and targeting or even overcoming the blood−brain barrier. The most commonly used techniques for particle characterization, including dynamic light scattering (DLS), differential sedimentation centrifugation, transmission electron microscopy (TEM), and SDS-PAGE, have been adopted to study corona formation in the past. Many newer tools, for example, a combination of capillary electrophoresis with mass spectrometry, are being used to study the corona composition. The comparison of interlaboratory results is a problem because of the lack of standard protocols. This has hindered the ability to obtain more precise information about the corona composition. That, in turn, affects our prospects to use nanoparticles as drugs/drug carriers. This overview is an attempt to assess our understanding of corona formation critically and to outline the complexities involved in gaining precise information. The discussion is largely focused on findings of the last year or so.

Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles

“…REPES analysis of the PMPC-PVBTMA system shows the growth of~200 nm aggregates over 1 to 10 h. This slight stability issue may be mitigated by increasing the degree of polymerization of PMPC, as the total length of the zwitterionic corona in micelles were previously shown to affect nanoparticle stabilization and delivery efficacy [33]. Nevertheless, because protein adsorption onto nanoparticle carriers in biological settings is a known design consideration for micelle assemblies [65,66], the prepared PCMs and zPCM show good overall resistance to destabilization by serum.…”

Insights into Characterization Methods and Biomedical Applications of Nanoparticle–Protein Corona

“…DCS is capable of separating the components of a mixture based on their densities and sizes, as larger and denser components require lower centrifugal forces to sediment. It is capable of analyzing the sizes of particles in the range of 0.01–40 μm and has been widely applied in measuring the sizes of NP-PC complexes [ 21 , 41 ]. For NPs with homogenous density and a simple shape, the particle size can be obtained directly, via the time taken by the NPs to travel from the center of a DCS disk through a defined viscous sucrose gradient under a strong centrifugal force to a detector placed at the outer rim of the disk [ 26 ].…”

Open questions: how do engineered nanomaterials affect our cells?

“…The biological identity is largely dictated by the protein corona, a protein coat on the surface of nanomaterials that forms through the adsorption of proteins from the blood or cell culture media. As the protein corona is the first to interface with the cell membrane, the biological identity can greatly impact the cellular uptake of nanomaterials [3].…”