Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

Arvizo, Rochelle R.; Giri, Karuna; Moyano, Daniel F.; Miranda, Oscar R.; Madden, Benjamin J.; McCormick, Daniel J.; Bhattacharya, Resham; Rotello, Vincent M.; Kocher, Jean Pierre A.; Mukherjee, Priyabrata

doi:10.1371/journal.pone.0033650

Cited by 91 publications

(89 citation statements)

References 47 publications

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“…107 Protein corona patterns, especially proteins which have powerful impacts on cellular uptake and biological responses, can be used to identify the overexpressed receptors on targeting cells as novel pharmacological approaches are discovered. 108 Moreover, the presence of different types of adsorbed proteins on NPs provides details about the biological fluids and blood components which NPs go through in the body. Thus, these information can be used for examining and diagnosing the physiological changes in our body related to protein modulation and structural deformation, such as in tumorigenesis and disease development.…”

Section: Future Perspectivesmentioning

confidence: 99%

Protein corona: a new approach for nanomedicine design

Nguyen¹,

Lee²

2017

IJN

534

343

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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.

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Section: Future Perspectivesmentioning

confidence: 99%

Protein corona: a new approach for nanomedicine design

Nguyen¹,

Lee²

2017

IJN

534

343

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“…The amount of protein adsorbed on the particle surface was obtained by subtracting the protein concentration in the supernatant from the initial protein concentration. 29 Diameter and zeta potentials of particles in suspension Dynamic light scattering (DLS) was used in order to reveal the hydrodynamic diameter of the agglomerates (Table 1) using a Zetasizer NS (Malvern Instruments, Malvern, UK). Dilute samples based on the suspensions described above (maximum 100 mg/L) were used in order to avoid multiple scattering.…”

Section: Quantification Of the Adsorbed Proteinsmentioning

confidence: 99%

The effect of blood protein adsorption on cellular uptake of anatase TiO2 nanoparticles

Allouni¹,

Gjerdet²,

Cimpan³

et al. 2015

IJN

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Protein adsorption onto nanoparticles (NPs) in biological fluids has emerged as an important factor when testing biological responses to NPs, as this may influence both uptake and subsequent toxicity. The aim of the present study was to quantify the adsorption of proteins onto TiO 2 NPs and to test the influence on cellular uptake. The surface composition of the particles was characterized by thermal analysis and by X-ray photoelectron spectroscopy. The adsorption of three blood proteins, ie, human serum albumin (HSA), γ-globulins (Glbs), and fibrinogen (Fib), onto three types of anatase NPs of different sizes was quantified for each protein. The concentration of the adsorbed protein was measured by ultraviolet-visible spectrophotometry using the Bradford method. The degree of cellular uptake was quantified by inductivity coupled plasma mass spectroscopy, and visualized by an ultra-high resolution imaging system. The proteins were adsorbed onto all of the anatase NPs. The quantity adsorbed increased with time and was higher for the smaller particles. Fib and Glbs showed the highest affinity to TiO 2 NPs, while the lowest was seen for HSA. The adsorption of proteins affected the surface charge and the hydrodynamic diameter of the NPs in cell culture medium. The degree of particle uptake was highest in protein-free medium and in the presence HSA, followed by culture medium supplemented with Glbs, and lowest in the presence of Fib. The results indicate that the uptake of anatase NPs by fibroblasts is influenced by the identity of the adsorbed protein.

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“…11 Specifically, the corona alters the shape, charge, hydrodynamic size, and interfacial composition of the nanomaterial influencing its biodistribution, activity, clearance, and toxicity. [15][16][17][18] Recently, we examined the formation of the complex protein corona (PC) on spherical silver nanoparticles (NPs) with a diameter of 20 or 110 nm coated with either polyvinylpyrrolidone (PVP) or citrate and suspended in typical cell culture media, Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum (FBS).…”

mentioning

confidence: 99%

A hyperspectral and toxicological analysis of protein corona impact on silver nanoparticle properties, intracellular modifications, and macrophage activation

Shannahan¹,

Podila²,

Brown³

2015

IJN

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The inevitable adsorption of biomolecules on nanomaterials results in the formation of a protein corona (PC), which modifies the nanoparticle (NP)–cell interface resulting in modified uptake, activity, clearance, and toxicity. While the physicochemical properties of the NP govern the composition of PC, the formation of PC in turn alters the characteristics of the NP by imparting a new unique “biological” identity. To assess how the PC influences AgNP properties, intracellular modifications, and cellular responses, we utilized a combination of hyperspectral and toxicological analyses. AgNPs were coated with a complex PC (multiple proteins, eg, 10% fetal bovine serum) or a simple PC (single protein, eg, bovine serum albumin [BSA]) and evaluated by hyperspectral and dynamic light scattering for modifications in AgNP properties. Mouse macrophages were exposed to AgNPs with PCs and examined for differences in uptake, cytotoxicity, and cell activation. Hyperspectral imaging revealed intracellular modifications to AgNPs that were found to spectrally match alterations in AgNPs following incubation in lysosomal fluid. Addition of the PC influenced AgNP uptake and cytotoxicity; however, hydrodynamic size and surface charge did not contribute to these responses. Assessments of all endpoints demonstrated differences between complex and BSA PC, suggesting that these responses are not purely driven by the primary protein component of the complex PC (ie, BSA). Alterations in cellular–NP uptake/interactions may be driven through cell surface receptor recognition of protein constituents that make up the PC rather than the physicochemical differences in AgNPs.

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Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

Cited by 91 publications

References 47 publications

Protein corona: a new approach for nanomedicine design

Protein corona: a new approach for nanomedicine design

The effect of blood protein adsorption on cellular uptake of anatase TiO2 nanoparticles

A hyperspectral and toxicological analysis of protein corona impact on silver nanoparticle properties, intracellular modifications, and macrophage activation

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