An Overview of Nanoparticle Protein Corona Literature

Abstract

The protein corona forms spontaneously on nanoparticle surfaces when nanomaterials are introduced into any biological system/fluid. Reliable characterization of the protein corona is, therefore, a vital step in the development of safe and efficient diagnostic and therapeutic nanomedicine products. 2134 published manuscripts on the protein corona are reviewed and a down‐selection of 470 papers spanning 2000–2021, comprising 1702 nanoparticle (NP) systems is analyzed. This analysis reveals: i) most corona studies have been conducted on metal and metal oxide nanoparticles; ii) despite their overwhelming presence in clinical practice, lipid‐based NPs are underrepresented in protein corona research, iii) studies use new methods to improve reliability and reproducibility in protein corona research; iv) studies use more specific protein sources toward personalized medicine; and v) careful characterization of nanoparticles after corona formation is imperative to minimize the role of aggregation and protein contamination on corona outcomes. As nanoparticles used in biomedicine become increasingly prevalent and biochemically complex, the field of protein corona research will need to focus on developing analytical approaches and characterization techniques appropriate for each unique nanoparticle formulation. Achieving such characterization of the nano‐bio interface of nanobiotechnologies will enable more seamless development and safe implementation of nanoparticles in medicine.

Identification of the Proteins Determining the Blood Circulation Time of Nanoparticles

“…NP Circulation Time. To determine the systemic circulation time of SPIONs−PVA with different molecular weights and surface chemistry, the NPs were administered to rats by tail− vein injection, and then, blood samples were collected at different times (5,10,20,30,45,60,90, or 120 and 120 or 240 min) depending on the SPION concentrations over time (more details of the protocols are in the SI). As different routes of injection can affect the blood circulation time, biodistribution, and corona decoration, all the NPs were injected by the tail vein and in a similar manner.…”

“…However, the application of NPs in medicine is often challenged by the biomolecular corona . NP surfaces are immediately covered by layers of biomolecules called the biomolecular/protein corona when they enter the human/animal body and are exposed to biological media (e.g., blood, lymphatic fluid). − The biomolecules adsorbed onto the NPs change their physicochemical properties and give them a new biological identity that is different from their synthetic identity. − Depending on the individual corona composition and its composition, the corona-coated NPs show different behaviors. − For example, the biomolecular corona may affect the pharmacokinetics of NPs such as plasma half-life and distribution . Among the biomolecules adsorbed on NPs, opsonins, such as complement factors and/or immunoglobulins (IgG), mediate NP binding to macrophages and phagocytes, and therefore, NP clearance is increased.…”

In Vitro and In Vivo Evaluation of the Pathology and Safety Aspects of Three- and Four-Way Junction RNA Nanoparticles

“…To summarize, the protein corona formation may have both positive and negative effects on RNA nanoparticles. The application of artificial intelligence in understanding protein corona formation on RNA nanoparticles has also been reported, ,, and a more detailed investigation of the relationship between RNA nanoparticles and protein corona is important. Our preliminary studies indicated that serum albumin binding is RNA shape, size, and stoichiometry dependent, and the corona formation of 4WJ might not be a major concern (Archie Bhullar and Peixuan Guo, unpublished results).…”

Stabilizing Polymer Coatings Alter the Protein Corona of DNA Origami and Can Be Engineered to Bias the Cellular Uptake

“…The use of nanomaterials at biological interfaces typically implies their exposure to complex milieus of extracellular proteins, which quickly adsorb onto the material surface and form a corona. , Such corona is known to have a multi-layered structure, commonly differentiating an inner “hard corona”, composed of proteins tightly bound to the nanoparticle surface, and an outer “soft corona” of highly dynamic nature, constituted by loosely bound, lower affinity proteins . These non-specific protein coatings may alter the shape, size, and surface characteristics of nanomaterials, endowing them with a completely new biological identity that impacts their interface interactions and resulting biological response .…”