Recent advances in the analysis of nanoparticle-protein coronas (original) (raw)

Protein Corona-Enabled Systemic Delivery and Targeting of Nanoparticles

The AAPS Journal, 2020

Upon systemic administration, nanoparticles encounter serum proteins in the biological system resulting in the formation of "protein corona" on the surface. Increased understanding of the relationship between nanoparticles' "chemical identity" and "biological identity" can contribute to improved clinical translation. Recent studies of protein corona composition on nanoparticles, including from our group, suggest that a strategic choice of materials can influence the types of protein adsorbed from plasma and lead to improved delivery efficiency. This mini-review reflects on the fundamental knowledge of nanoparticle protein corona and highlights the recent applications of protein corona on nanoparticles' systemic circulation, cell, and tissue-specific delivery. Important considerations on the safety and efficacy aspects pertaining to the exploration of nanoparticle protein corona's targeting effect are also summarized. Finally, the future perspectives of protein corona research are discussed.

How protein coronas determine the fate of engineered nanoparticles in biological environment

Arhiv za higijenu rada i toksikologiju, 2017

Nanomedicine is a booming medical field that utilises nanoparticles (NPs) for the development of medicines, medical devices, and diagnostic tools. The behaviour of NPs in vivo may be quite complex due to their interactions with biological molecules. These interactions in biological fluids result in NPs being enveloped by dynamic protein coronas, which serve as an interface between NPs and their environment (blood, cell, tissue). How will the corona interact with this environment will depend on the biological, chemical, and physical properties of NPs, the properties of the proteins that make the corona, as well as the biological environment. This review summarises the main characteristics of protein corona and describes its dynamic nature. It also presents the most common analytical methods to study the corona, including examples of protein corona composition for the most common NPs used in biomedicine. This knowledge is necessary to design NPs that will create a corona with a desire...

Physical−Chemical Aspects of Protein Corona: Relevance to in Vitro and in Vivo Biological Impacts of Nanoparticles

Journal of the American Chemical Society, 2011

It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.

The impact of nanoparticle protein corona on cytotoxicity, immunotoxicity and target drug delivery

Nanomedicine (London, England), 2016

In a perfect sequence of events, nanoparticles (NPs) are injected into the bloodstream where they circulate until they reach the target tissue. The ligand on the NP surface recognizes its specific receptor expressed on the target tissue and the drug is released in a controlled manner. However, once injected in a physiological environment, NPs interact with biological components and are surrounded by a protein corona (PC). This can trigger an immune response and affect NP toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the NP-PC interactions and discuss how the PC can be used to modulate both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.

Quantitative comparison of the protein corona of nanoparticles with different matrices

International Journal of Pharmaceutics: X

Nanoparticles (NPs) are paving the way for improved treatments for difficult to treat diseases diseases; however, much is unknown about their fate in the body. One important factor is the interaction between NPs and blood proteins leading to the formation known as the "protein corona" (PC). The PC, consisting of the Hard (HC) and Soft Corona (SC), varies greatly based on the NP composition, size, and surface properties. This highlights the need for specific studies to differentiate the PC formation for each individual NP system. This work focused on comparing the HC and SC of three NPs with different matrix compositions: a) polymeric NPs based on poly(lacticco-glycolic) acid (PLGA), b) hybrid NPs consisting of PLGA and Cholesterol, and c) lipidic NPs made only of Cholesterol. NPs were formulated and characterized for their physico-chemical characteristics and composition, and then were incubated in human plasma. In-depth purification, identification, and statistical analysis were then performed to identify the HC and SC components. Finally, similar investigations demonstrated whether the presence of a targeting ligand on the NP surface would affect the PC makeup. These results highlighted the different PC fingerprints of these NPs, which will be critical to better understand the biological influences of the PC and improve future NP designs.

A review of the current understanding of nanoparticles protein corona composition

Medicine and Pharmacy Reports, 2020

Upon entering into the biological environments, the surface of the nanoparticles is immediately coated with proteins and form the so-called a protein corona due to which a nanoparticle changes its "synthetic" identity to a new "biological" identity. Different types of nanoparticles have different protein binding profiles, which is why they have different protein corona composition and therefore it cannot be said that there is a universal protein corona. The composition and amount of protein in the corona depends on the physical and chemical characteristics of the nanoparticles, the type of biological medium and the exposure time. Protein corona increases the diameter but also changes the composition of the surface of the nanoparticles and these changes affect biodistribution, efficacy, and toxicity of the nanoparticles.

Merging Worlds of Nanomaterials and Biological Environment: Factors Governing Protein Corona Formation on Nanoparticles and Its Biological Consequences

Nanoscale Research Letters, 2015

Protein corona has became a prevalent subject in the field of nanomedicine owing to its diverse role in determining the efficiency, efficacy, and the ultimate biological fate of the nanomaterials used as a tool to treat and diagnose various diseases. For instance, protein corona formation on the surface of nanoparticles can modify its physicochemical properties and interfere with its intended functionalities in the biological microenvironments. As such, much emphasis should be placed in understanding these complex phenomena that occur at the bio-nano interface. The main aim of this review is to present different factors that are influencing protein-nanoparticle interaction such as physicochemical properties of nanoparticle (i.e., size and size distribution, shape, composition, surface chemistry, and coatings) and the effect of biological microenvironments. Apart from that, the effect of ignored factors at the bio-nano interface such as temperature, plasma concentration, plasma gradient effect, administration route, and cell observer were also addressed.

Modification of the protein corona–nanoparticle complex by physiological factors

Materials Science and Engineering: C, 2016

Nanoparticle (NP) effects in a biological system are driven through the formation and structure of the protein corona-NP complex, which is dynamic by nature and dependent upon factors from both the local environment and NP physicochemical parameters. To date, considerable data has been gathered regarding the structure and behavior of the protein corona in blood, plasma, and traditional cell culture medium. However, there exists a knowledge gap pertaining to the protein corona in additional biological fluids and following incubation in a dynamic environment. Using 13 nm gold NPs (AuNPs), functionalized with either polyethylene glycol or tannic acid, we demonstrated that both particle characteristics and the associated protein corona were altered when exposed to artificial physiological fluids and under dynamic flow. Furthermore, the magnitude of observed behavioral shifts were dependent upon AuNP surface chemistry. Lastly, we revealed that exposure to interstitial fluid produced protein corona modifications, reshaping of the nano-cellular interface, modified AuNP dosimetry, and induction of previously unseen cytotoxicity. This study highlights the need to elucidate both NP and protein corona behavior in biologically representative environments in an effort to increase accurate interpretation of data and transfer of this knowledge to efficacy, behavior, and safety of nano-based applications.

Impact of Protein Corona on the Biological Identity of Nanomedicine: Understanding the Fate of Nanomaterials in the Biological Milieu

Biomedicines

Nanoparticles (NPs) in contact with a biological medium are rapidly comprehended by a number of protein molecules resulting in the formation of an NP–protein complex called protein corona (PC). The cell sees the protein-coated NPs as the synthetic identity is masked by protein surfacing. The PC formation ultimately has a substantial impact on various biological processes including drug release, drug targeting, cell recognition, biodistribution, cellular uptake, and therapeutic efficacy. Further, the composition of PC is largely influenced by the physico-chemical properties of NPs viz. the size, shape, surface charge, and surface chemistry in the biological milieu. However, the change in the biological responses of the new substrate depends on the quantity of protein access by the NPs. The PC-layered NPs act as new biological entities and are recognized as different targeting agents for the receptor-mediated ingress of therapeutics in the biological cells. The corona-enveloped NPs ha...

Surface chemistry and serum type both determine the nanoparticle-protein corona

Journal of Proteomics, 2015

The protein corona that forms around nanoparticles in vivo is a critical factor that affects their physiological response. The potential to manipulate nanoparticle characteristics such that either proteins advantageous for delivery are recruited and/or detrimental proteins are avoided offers exciting possibilities for improving drug delivery. In this work, we used nanoliquid chromatography tandem mass spectrometry to characterize the corona of five lipid formulations after incubation in mouse and human plasma with the hope of providing data that may contribute to a better understanding of the role played by both the nanoparticle properties and the physiological environment in recruiting specific proteins to the corona. Notably, we showed that minor changes in the lipid composition might critically affect the protein corona composition demonstrating that the surface chemistry and arrangement of lipid functional groups are key players that regulate the liposome-protein interactions. Notably, we provided evidence that the protein corona that forms around liposomes is strongly affected by the physiological environment, i.e., the serum type. These results are likely to suggest that the translation of novel pharmaceutical formulations from animal models to the clinic must be evaluated on a case-by-case basis.