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In the presence of biological matrices, engineered nanomaterials, such as TiO2, develop a biomolecular corona composed of lipids, proteins, etc. In this study, we analyzed the biocorona formed on the food grade TiO2 (E171) going through an in vitro simulated gastrointestinal digestion system in either a fasting food model (FFM), a standardized food model (SFM), or a high fat food model (HFFM). Lipids and proteins were extracted from the biocorona and underwent untargeted lipidomic and label-free shotgun proteomic analyses. Our results showed that the biocorona composition was different before and after food digestion. After digestion, more diverse lipids were adsorbed compared to proteins, most of which were the enzymes added to the simulated digestion system. The corona lipid profile was distinct from the digested food model they presented in, although similarity in the lipid profiles between the corona and the food matrix increased with the fat content in the food model. The corona formed in the two low-fat environments of FFM and SFM shared a higher degree of similarity while very different from their corresponding matrix, with some lipid species adsorbed with high enrichment factors, indicating specific interaction with the TiO2 surface outperforming lipid matrix concentration in determination of corona formation. Formation of the biocorona may have contributed to the reduced oxidative stress as well as toxicological impacts observed in cellular studies. The present work is the first to confirm persistent adsorption of biomolecules could occur on ingested nanomaterials in food digestae. More future studies are needed to study the in vivo impacts of the biocorona, and shed lights on how the biocorona affects the biotransformations and fate of the ingested nanomaterials, which may impose impacts on human health.

Abstract Plant food bioactives (PFBs) offer immense health benefits with a greater scope for treating various life‐threatening diseases and lifestyle disorders. Knowing their therapeutic potentials, a lot of research works are being carried out on formulating PFBs‐loaded nano delivery systems (NDSs) to enhance their bioefficacy. However, limited information are available on the interactions occurring at the nano‐bio interface. Therefore, studies on nano‐bio interactions are of immense importance towards designing/formulating effective NDSs for PFBs. Understanding the significance of nano‐bio interface of food bioactive‐loaded NDSs would help us to predict the formation of biocorona as well as the correlation between the nanoparticles and their surrounding environments that are influenced by the NDS's physicochemical properties. The physicochemical characteristics of NDSs like size, shape, and surface charge will decide their fate in the biological fluids and have been discussed in detail. As the bioactives‐loaded NDS enters the gastrointestinal tract, formation of biocorona including protein and enzyme corona at the nano‐bio interface will takes place. Subsequently, the fate of PFBs‐loaded NDSs influences the absorption, distribution, metabolism, and excretion (ADME) processes and thereby its bioavailability, bioefficacy, and biosafety. The current review focuses on understanding the journey of PBFs‐loaded NDSs, the nature of interactions happening at nano‐bio interface, and its pharmacokinetics properties. In addition, a specific case study approach on curcumin‐loaded NDSs, and its reported interactions at nano‐bio interface, including ADME mechanism are comprehensively presented.

It is well known that when nanoparticles interact with biological fluids, a layer of proteins and biological components forms on them. This layer may alter the biological fate and efficiency of the nanomaterial. Recent studies have shown that illness states have a major impact on the structure of the biocorona, sometimes referred to as the "personalized protein corona." Physiological factors like illness, which impact the proteome and metabolome pattern and result in conformational changes in proteins, give rise to this structure of discrimination in biocorona decoration. Improving the efficiency of precise platforms for developing new molecular biomarkers for accurate illness diagnosis is vitally necessary. The biocorona pattern's discrimination may be a diagnostic tool for designing biosensors. As a result, in this review, we summarize the most current studies on the relationship between physiological conditions and the variety of biocorona patterns that influence the biological responses of nanosystems. The biocorona pattern's flexibility may provide new research directions and be utilized to create nanoparticle-based therapeutic and diagnostic products suited to certain physiological situations. Different biological situation such as diverse disease, pregnancy and addiction generate different biocorona patterns, so discrimination in biocorona pattern could be used as disease biomarker and diagnostic agent in biosensor design. [Display omitted] • Protein corona alter the biological fate and efficiency of the nanomaterial. • Different physiological conditions can change proteome and metabolome pattern. • Biological situation is determinative of protein corona around nanoparticles. • Personalized protein corona can be used in disease diagnostic. [ABSTRACT FROM AUTHOR]

The functional activities of gold nanoparticles (AuNPs) on biological systems depend on their physical-chemical properties and their surface functionalizations. Within a biological environment and depending on their surface characteristics, NPs can adsorb biomolecules (mostly proteins) present in the microenvironment, thereby forming a dynamic biomolecular corona on the surface. The presence of this biocorona changes the physical-chemical and functional properties of the NPs and how it interacts with cells. Here, we show that primary human epidermal keratinocytes (HEK) exposed in culture to branched polyethyleneimine (BPEI)-AuNPs, but not to lipoic acid (LA)-AuNPs, show potent particle uptake, decreased cell viability and enhanced production of inflammatory factors, while the presence of a human plasma-derived biocorona decreased NPs uptake and rescued cells from BPEI-AuNP-induced cell death. The mechanistic study revealed that the intracellular oxidative level greatly increased after the BPEI-AuNPs treatment, and the transcriptomic analysis showed that the dominant modulated pathways were related to oxidative stress and an antioxidant response. The stress level measured by flow cytometry also showed a significant decrease in the presence of a biocorona. Further anaylsis discovered that nuclear factor erythroid-2 related factor (Nrf2), a major regulator of anti-oxidant and anti-inflammatory genes, as the key factor related to the AuNPs induced oxidative stress and inflammation. This study provides futher understanding into the mechanisms on how NPs-induced cellular stress and reveals the protective effects of a biocorona on inflammatory responses in HEK at the molecular level, which provides important insights into the biological responses of AuNPs and their biocorona. [Display omitted] • BPEI- but not LA-AuNPs caused potent particle uptake, induced cytotoxicity, enhanced inflammation in human keratinocytes. • Intracellular ROS that induced by BPEI-AuNPs was the mainly reason for these adverse effects. • Nrf2 was the key mediator related to the BPEI-AuNPs induced oxidative stress and inflammation. • The presence of biocorona suppressed the adverse effects caused by BPEI-AuNPs in keratinocytes in vitro. [ABSTRACT FROM AUTHOR]

Nanomaterials offer promising solutions as drug delivery systems and imaging agents in response to the demand for better therapeutics and diagnostics. However, the limited understanding of the interaction between nanoparticles and biological entities is currently hampering the development of new systems and their applications in clinical settings. Proteins and lipids in biological fluids are known to complex with nanoparticles to form a "biomolecular corona". This has been shown to affect particles' morphology and behavior in biological systems and their interactions with cells. Hence, understanding how nanomaterials' physicochemical properties affect the formation and composition of this biocorona is a crucial step. This work evaluates existing literature on how morphology (size and shape), and surface chemistry (charge and hydrophobicity) of nanoparticles influence the formation of protein corona. The latest evidence suggest that although surface charge promotes the interaction with proteins and lipids, surface chemistry plays a leading role in determining the affinity of the nanoparticle for biomolecules and, ultimately, the composition of the corona. More recently the study of additional nanoparticles' properties like shape and surface chirality have demonstrated a significant effect on protein corona architecture, providing new tools to tailor biomolecular corona formation. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesToxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials [ABSTRACT FROM AUTHOR]

Abstract The major interest in nanoparticles as an application platform for biotechnology arises from their high surface-to-volume ratio. Iron oxide nanoparticles (IONPs) are particularly appealing due to their superparamagnetic behavior, which enables bioseparation using external magnetic fields. In order to design advanced biomaterials, improve binding capacities and develop innovative processing solutions, a thorough understanding of the factors governing organic-inorganic binding in solution is critical but has not yet been achieved, given the wide variety of chemical and physical influences. This paper offers a critical review of experimental studies of the interactions between low cost IONPs (bare iron oxides, silica-coated or easily-functionalized surfaces) and the main groups of biomolecules: proteins, lipids, nucleic acids and carbohydrates. Special attention is devoted to the driving forces and interdependencies responsible of interactions at the solid-liquid interface, to the unique structural characteristics of each biomolecular class, and to environmental conditions influencing adsorption. Furthermore, studies focusing on mixtures, which are still rare, but absolutely necessary to understand the biocorona, are also included. This review concludes with a discussion of future work needed to fill the gaps in knowledge of bio-nano interactions, seeking to improve nanoparticles’ targeting capabilities in complex systems, and to open the door for multipurpose recognition and bioseparation processes.

Phytonanotechnology is lately gaining increased interest owing to its potential to modernize agriculture for better yield and nutritional quality. Consequently, Nano-Agri products like nano-biosensors, nano-carriers, and growth augmenters are being developed and applied. However, the limited knowledge of molecular interactions taking place at nano-bio interface remains a major concern. The nanotechnological interventions for healthier crops could rather turn out tobe risky and inefficient in the absence ofclear understanding of molecular mechanisms of nano-bio interactions. Upon entry into tissues or cells, nanoparticles (NPs) adsorb biomolecules forming a biocorona which determines NP uptake, translocation, and reactivity. The composition of biocorona is dependent on the physicochemical characteristics of the NPs, their surroundings, and the interaction time. Recent nascent studies in plants showed the potential of biocorona to influence major cellular pathways or plant responses like energy synthesis, pathogenesis, stress tolerance, and leaf senescence. This mini-review aims at summarizing the recent application of phytonanotechnology, the current status of biocorona studies with an overview of research bottlenecks and future prospects. [ABSTRACT FROM AUTHOR]

Abstract Background Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. Results Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. Conclusion In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.

The increasing use of multiwalled carbon nanotubes (MWCNTs) could increase the risk of allergic lung disease in occupational or consumer settings. We previously reported that MWCNTs exacerbated allergic lung disease in mice induced by extract from house dust mites (HDM), a common cause of asthma in humans. Because MWCNTs avidly bind biomolecules to form protein coronas that can modify immunotoxicity, we hypothesized that exacerbation of allergic lung disease in mice caused by coexposure to MWCNTs and HDM extract was due to the formation of an allergen corona. In a first set of experiments, male and female C57BL/6J mice were coexposed to MWCNTs and HDM extract over 3 weeks compared to MWCNTs or HDM extract alone. In a second set of experiments, mice were exposed to pristine MWCNTs or MWCNTs with an HDM allergen corona (HDM-MWCNTs). HDM-MWCNTs were formed by incubating MWCNTs with HDM extract, where ∼7% of proteins adsorbed to MWCNTs, including Der p 1 and Der p 2. At necropsy, bronchoalveolar lavage fluid was collected from lungs to assess lactate dehydrogenase, total protein and inflammatory cells, while lung tissue was used for histopathology, qPCR, and Western blotting. Compared to MWCNTs or HDM extract alone, coexposure to MWCNTs and HDM extract or exposure to HDM-MWCNTs increased pathological outcomes associated with allergic lung disease (eosinophilia, fibrosis, mucous cell metaplasia), increased mRNAs associated with fibrosis ( Col1A1 , Arg1 ) and enhanced STAT6 phosphorylation in lung tissue. These findings indicated that exacerbation of HDM-induced allergic lung disease by MWCNTs is due to an allergen corona.

The importance of polymeric nanocarriers in the field of drug delivery is ever-increasing, and the accurate characterization of their properties is paramount to understand and predict their behavior. Asymmetric flow field-flow fractionation (AF4) is a fractionation technique that has gained considerable attention for its gentle separation conditions, broad working range, and versatility. AF4 can be hyphenated to a plurality of concentration and size detectors, thus permitting the analysis of the multifunctionality of nanomaterials. Despite this potential, the practical information that can be retrieved by AF4 and its possible applications are still rather unfamiliar to the pharmaceutical scientist. This review was conceived as a primer that clearly states the "do's and don'ts" about AF4 applied to the characterization of polymeric nanocarriers. Aside from size characterization, AF4 can be beneficial during formulation optimization, for drug loading and drug release determination and for the study of interactions among biomaterials. It will focus mainly on the advances made in the last 5 years, as well as indicating the problematics on the consensus, which have not been reached yet. Methodological recommendations for several case studies will be also included. [ABSTRACT FROM AUTHOR]

Background: Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure. Results: Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona. Conclusion: In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications. [ABSTRACT FROM AUTHOR]

The protein corona is a natural protein layer spontaneously formed around nanomaterials when exposed to biological media. This layer can alter the nanosystems' biological performance, particularly their tissue accumulation, cellular uptake, clearance by the immune system, toxicity, and even the release profile of their payloads. Hence, the characterization of this protein layer has become a critical step when developing a new nanomedicine. The modification of the nanosystem fate by the protein corona, systematically ignored in the vast majority of the nanotechnology-based research, may have contributed to the low in vitro/in vivo correlation. Actually, the protein corona of polymeric nanosystems has been scarcely studied in the literature, and most studies have been focused instead on metallic nanoparticles and liposomes. In this review, we analyzed the influence of the physicochemical properties and composition of the polymeric nanosystems on the protein layer deposited around them. In addition, we present some recommendations on how to perform the protein corona studies of polymeric nanoparticles, which, hopefully, will contribute to obtain more reliable and reproducible data in the future. [ABSTRACT FROM AUTHOR]

As nanoparticles have been found to cause a range of harmful impacts in biota, understanding processes and transformations which may stabilize and increase their persistence time in the environment are of great importance. As nanoparticles carried in riverine or wastewaters will eventually reach estuaries, understanding their behavior and transport potential in this transition zone from fresh to marine waters is essential, particularly as estuaries are sensitive ecological zones, oftentimes encompassing ornithologically important areas. In this direction, we report on the influence of combined gradients of riverine and marine natural organic matter (NOM) on the temporal stability of biocorona-encapsulated silver nanoparticles in terms of ion release kinetics. In parallel, salinity, pH and oxygen saturation were simultaneously varied to create a model to mimic the complex estuarine environment. While humic acid (HA) and alginate (Alg) disrupted the stabilizing ability of the nanoparticle protein corona to a greater and lesser degree, respectively, they slowed the rate of ion release in freshwater at pH 6.6 and in saltwater at pH 8, respectively, while oxygen saturation was also found to be an important factor. Thus, as the type of NOM changes with pH along a salinity gradient in an estuary, conditions required to increase the persistence time of nanoparticles are serendipitously met, with greater colloidal stability achieved in cases where there is more rapid replacement of HA with Alg. Despite the strong gradients in ionic strength, pH and oxygen saturation, the protein corona was not sufficiently disrupted at the nanoparticle surface to be substituted by NOM indicating the greater adsorption energy of the protein’s hydrophobic domains. Ultimately, it is the specific NOM profile of individual estuaries that may provide the best indicator for predicting the stability and persistence of silver nanoparticles as they transition from fresh to salt water environments.

Extensive exploitation of titanium dioxide nanoparticles (TiO2NPs) augments rapid release into the marine environment. When in contact with the body fluids of marine invertebrates, TiO2NPs undergo a transformation and adhere various organic molecules that shape a complex protein corona prior to contacting cells and tissues. To elucidate the potential extracellular signals that may be involved in the particle recognition by immune cells of the sea urchin Paracentrotus lividus, we investigated the behavior of TiO2NPs in contact with extracellular proteins in vitro. Our findings indicate that TiO2NPs are able to interact with sea urchin proteins in both cell-free and cell-conditioned media. The two-dimensional proteome analysis of the protein corona bound to TiO2NP revealed that negatively charged proteins bound preferentially to the particles. The main constituents shaping the sea urchin cell-conditioned TiO2NP protein corona were proteins involved in cellular adhesion (Pl-toposome, Pl-galectin-8, Pl-nectin) and cytoskeletal organization (actin and tubulin). Immune cells (phagocytes) aggregated TiO2NPs on the outer cell surface and within well-organized vesicles without eliciting harmful effects on the biological activities of the cells. Cells showed an active metabolism, no oxidative stress or caspase activation. These results provide a new level of understanding of the extracellular proteins involved in the immune-TiO2NP recognition and interaction in vitro, confirming that primary immune cell cultures from P. lividus can be an optional model for swift and efficient immune-toxicological investigations.

Silica nanoparticles (SiO 2 NPs) are widely used engineered materials that warrant their obvious environmental exposure risk. Our previous study has shown that different routes of SiO 2 NP exposure on the glycogen synthase kinase 3 beta (GSK3β) activity were related to the serum proteins enriched on the surface of SiO 2 NPs, which implied that a particular protein in the serum changed the inherent toxic behavior of SiO 2 NPs and inhibited the activation of GSK3β by SiO 2 NPs. Here, we identified that the SiO 2 NP surface enriched a large amount of apolipoprotein E (ApoE), and the ApoE protein corona bound to the lipoprotein receptor-related protein 1 (LRP1) to inactivate GSK3β, thereby reducing the damage of SiO 2 NPs to the brain. This work presented the first evidence that specific biocorona reduced the toxicity of SiO 2 NPs at the molecular level, which helped to elucidate the role of specific corona components on nanotoxicity.

Abstract Multidrug-resistant bacterial infections are a global health threat. Nanoparticles are thus investigated as novel antibacterial agents for clinical practice, including wound dressings and implants. We report that nanoparticles' bactericidal activity strongly depends on their physical binding to pathogens, including multidrug-resistant primary clinical isolates, such as Staphylococcus aureus , Klebsiella pneumoniae or Enterococcus faecalis. Using controllable nanoparticle models, we found that nanoparticle-pathogen complex formation was enhanced by small nanoparticle size rather than material or charge, and was prevented by 'stealth' modifications. Nanoparticles seem to preferentially bind to Gram-positive pathogens, such as Listeria monocytogenes, S. aureus or Streptococcus pyrogenes, correlating with enhanced antibacterial activity. Bacterial resistance to metal-based nanoparticles was mediated by biomolecule coronas acquired in pathophysiological environments, such as wounds, the lung, or the blood system. Biomolecule corona formation reduced nanoparticles' binding to pathogens, but did not impact nanoparticle dissolution. Our results provide a mechanistic explanation why nano-sized antibiotics may show reduced activity in clinically relevant environments, and may inspire future nanoantibiotic designs with improved and potentially pathogen-specific activity. [ABSTRACT FROM AUTHOR]

Over the last decades, the growth in nanotechnology has provoked an increase in the number of its applications and consumer products that incorporate nanomaterials in their formulation. Metal nanoparticles are released to the marine environment and they can interact with cells by colloids forces establish a nano-bio interface. This interface can be compatible or generate bioadverse effects to cells. The daily use of CeO 2 nanoparticles (CeO 2 NPs) in industrial catalysis, sunscreen, fuel cells, fuel additives and biomedicine and their potential release into aquatic environments has turned them into a new emerging pollutant of concern. It is necessary to assess of effects of CeO 2 NPs in aquatic organisms and understand the potential mechanisms of action of CeO 2 NP toxicity to improve our knowledge about the intrinsic and extrinsic characteristic of CeO 2 NPs and the interaction of CeO 2 NPs with biomolecules in different environment and biological fluids. The conserved innate immune system of bivalves represents a useful tool for studying immunoregulatory responses when cells are exposed to NPs. In this context, the effects of two different CeO 2 NPs with different physico-chemical characteristics (size, shape, zeta potential and Ce +3 /Ce +4 ratio) and different behavior with biomolecules in plasma fluid were studied in a series of in vitro assays using primary hemocytes from Mytilus galloprovincialis . Different cellular responses such as lysosome membrane stability, phagocytosis capacity and extracellular reactive oxygen species (ROS) production were evaluated. Our results indicate that the agglomeration state of CeO 2 NPs in the exposure media did not appear to have a substantial role in particle effects, while differences in shape, zeta potential and biocorona formation in NPs appear to be important in provoking negative impacts on hemocytes. The negative charge and the rounded shape of CeO 2 NPs, which formed Cu, Zn-SOD biocorona in hemolymph serum (HS), triggered higher changes in the biomarker of stress (LMS) and immunological parameters (ROS and phagocytosis capacity). On the other hand, the almost neutral surface charge and well-faceted shape of CeO 2 NPs did not show either biocorona formation in HS under tested conditions or significant responses. According to the results, the most relevant conclusion of this work is that not only the physicochemical characterization of CeO 2 NPs plays an important role in NPs toxicity but also the study of the interaction of NPs with biological fluids is essential to know it behavior and toxicity at cellular level. [ABSTRACT FROM AUTHOR]

RNA Interference (RNAi) is a potentially useful tool to correct the detrimental effects of faulty genes; several RNAi are undergoing clinical evaluation in various diseases. The present study identified the relative contributions of three mechanisms by which polyanion drugs reduced the gene silencing activity of Lipoplex, a complex of small interfering RNA (siRNA) and cationic liposomes. The study used a siRNA against the chemoresistance gene survivin and two model polyanion drugs (suramin, heparin). Products of Lipoplex destabilization were separated, identified, and/or quantified using ultrafiltration, gel electrophoresis, and RT-qPCR (quantitative reverse transcription polymerase chain reaction). Cell binding and endocytosis of fluorescence-labeled Lipoplex and the amount of siRNA at its site of action RISC (RNA-induced silencing complex) were evaluated using endocytosis markers, confocal microscopy, quantitative image analysis, immunoprecipitation, and RT-qPCR. The results show suramin and heparin exerted multiple concentration-dependent effects. First, these agents altered several Lipoplex properties (i.e., reduced particle size, changed surface charge, modified composition of protein biocorona). Second, both caused Lipoplex destabilization to release double- and single-strand siRNA and/or smaller siRNA-lipid complexes with reduced siRNA cargo. Third, both prevented the cell surface binding and internalization of Lipoplex, diminished the siRNA concentration in RISC, and retarded the mRNA knockdown. Suramin and heparin yielded qualitatively and quantitatively different results. Analysis of the experimental results of suramin using quantitative pharmacology (QP) modeling indicated the major cause of gene silencing activity loss depended on drug concentration, changing from inhibition of endocytosis at lower concentration (accounting for 60% loss at ~ 9 μM) to inhibition of cell surface binding and loss of siRNA cargo at higher concentrations (accounting for 64% and 27%, respectively, at 70 μM). In summary, the present study demonstrates the complex and dynamic interactions between polyanions and Lipoplex, and the use of QP modeling to delineate the contributions of three mechanisms to the eventual loss of gene silencing activity. [ABSTRACT FROM AUTHOR]

This study investigated the role of nanoparticle size and surface chemistry on biocorona composition and its effect on uptake, toxicity and cellular responses in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona proteins among the various AuNP, revealing largely surface chemistry-dependent signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size distribution analysis revealed the relative instability and aggregation inducing potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular dichroism analysis showed surface chemistry-dependent conformational changes of proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC formation. Cell viability studies demonstrated dose-dependent toxicity of BPEI-AuNP. Transcriptional profiling studies revealed 126 genes, from 13 biological pathways, to be differentially regulated by 40 nm bare and PC-bound BPEI-AuNP (PC-BPEI-AuNP). Furthermore, PC formation relieved the toxicity of cationic BPEI-AuNP by modulating expression of genes involved in DNA damage and repair, heat shock response, mitochondrial energy metabolism, oxidative stress and antioxidant response, and ER stress and unfolded protein response cascades, which were aberrantly expressed in bare BPEI-AuNP-treated cells. NP surface chemistry is shown to play the dominant role over size in determining the biocorona composition, which in turn modulates cell uptake, and biological responses, consequently defining the potential safety and efficacy of nanoformulations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Carbohydrates adsorbed to TiO 2 nanoparticle surfaces and formed biocoronas. • The absorption capacity of the carbohydrates depended on their molecular weights. • Nanoparticle morphology, charge, and aggregation changed after carbohydrate adsorption. • These changes may impact the gastrointestinal fate of TiO 2 nanoparticles. Titanium dioxide (TiO 2) is commonly used as food whitening in candies, chocolates, and cakes with high carbohydrate contents. The potential interaction between the food carbohydrate and food grade TiO 2 nanoparticle was little known. Therefore, we explored the interaction between TiO 2 nanoparticles and seven common carbohydrates, including monosaccharides, disaccharides, and polysaccharides. The result showed that all the carbohydrates tested interacted with the surfaces of the TiO 2 nanoparticles and formed biocoronas. TEM and SEM images provided information about the morphology formation of biocoronas. The surface potential and size of the TiO 2 nanoparticles altered after interacting with the carbohydrates. FTIR spectroscopy and QCM-D findings showed insights into the molecular origin and nature interaction between TiO 2 and carbohydrates. The results illustrated that TiO 2 nanoparticles can interact with carbohydrates, enter the body as a food additive, and interact with food matrix for a series of reactions. Compared with monosaccharides or disaccharides, food polysaccharides have stronger adsorption on the surface of nanoparticles. This is a preliminary judgment for the subsequent in vitro simulated digestion. Our result could be useful for understanding and controlling the behavior of nanoparticles in food and the human gut. [ABSTRACT FROM AUTHOR]

Magnetic nanoparticles are an attractive bioseparation tool due to their magnetic susceptibility and high adsorption capacity for different types of molecules. A major challenge for separation is to generate selectivity for a target molecule, or for a group of molecules in complex environments such as cell lysates. It is crucial to understand the factors that determine the targets' adsorption behavior in mixtures for triggering intended interactions and selectivity. Here we use a model system containing three molecules, each of them a common representative of the more abundant types of macromolecules in living systems: sodium oleate (SO), a fatty acid; bovine serum albumin (BSA), a protein; and dextran, a polysaccharide. Our results show that (a) the BSA adsorption capacity on the iron oxide material depends markedly on the pH, with the maximum capacity at the pI of the protein (0.39 g g MNP -1 ); (b) sodium oleate, a strongly negatively charged molecule, an organic anion, renders a maximum adsorption capacity of 0.40 g g MNP -1 , even at pHs at which oleate as well as the nanoparticle surface are negatively charged; (c) the adsorbed masses of dextran, a neutral sugar, are lower than for the other two molecules, between 0.09 and 0.13 g g MNP -1 , regardless of the system's pH. We observe an unexpected behavior in mixtures: SO completely prevents the adsorption of BSA, and dextran decreases the adsorption of the other competitors, SO and BSA, while adsorbing at the same capacities, unaffected by either the presence of the other two molecules or the pH. BSA does not decrease the oleate adsorption capacity. We demonstrate the essential role of pH in the adsorption of BSA (a protein) and SO (a fatty acid), as well as its impact in the structural organization of the oleate molecules in water. Moreover, we present exciting data on the adsorption of the molecules in competition, revealing the need to focus on interaction studies in more complex environments. This study attempts to open the scope of the current research of bio-nano interactions to not only proteins but also to mixtures, and generally to molecules with other physicochemical characteristics. Furthermore, we contribute to the understanding of multicomponent systems with the vision set in enhancing biomass exploitation and biofractionation processes.

Aim: To assess the impact of biocorona kinetics on expected tissue distribution of nanoparticles (NPs) across species. Materials & methods: The potential fate of NPs in vivo is described through a simple and descriptive pharmacokinetic model using rate processes dependent upon basal metabolic rate coupled to dynamics of protein corona. Results: Mismatch of time scales between interspecies allometric scaling and the kinetics of corona formation is potentially a fundamental issue with interspecies extrapolations of NP biodistribution. The impact of corona evolution on NP biodistribution across two species is maximal when corona transition half-life is close to the geometric mean of NP half-lives of the two species. Conclusion: While engineered NPs can successfully reach target cells in rodent models, the results may be different in humans due to the fact that the longer circulation time allows for further biocorona evolution. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO 2) particles are widely employed in foods and supplements as lightening agents. A substantial fraction of the particles in commercial TiO 2 ingredients fall within the nanoscale, i.e., they have diameters below 100 nm. A biocorona can form around TiO 2 particles when they are incorporated into food matrices containing plant proteins. In this study, we investigated the molecular interactions between two hydrophobic plant proteins (gliadin and zein) and four types of surface-modified TiO 2 nanoparticles (TCN, TCN-1, TCN-2 and TCN-3). Ultraviolet–visible absorption, fluorescence quenching, and Fourier transform infrared spectroscopy indicated that the plant proteins interacted with the surfaces of the TiO 2 nanoparticles, resulting in changes in their molecular conformations. Quartz crystal microbalance analysis indicated that the mass of the hard corona increased as the number of hydroxyl groups on the surfaces of the TiO 2 nanoparticles increased, which implied that hydrogen bonding played an important role in the formation of the biocorona. These results provide a better understanding of the interactions that may occur in food matrices containing both plant proteins and TiO 2 nanoparticles. [Display omitted] • Plant proteins interact with TiO 2 nanoparticles in food matrices to form biocoronas. • These biocorona can be divided into 'hard' and 'soft' layers. • Hydrogen bonds play an important role in biocorona formation. • Protein adsorption/desorption depended on surface properties of the nanoparticles. • Surface modifications affected the aggregation degree of the nanoparticles. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are produced by all cell types and serve as biological packets delivering a wide variety of molecules for cell-to-cell communication. However, the biology of the EV extravesicular surface domain that we have termed EV 'biocorona' remains underexplored. Upon cell secretion, EVs possess an innate biocorona containing membrane integral and peripheral constituents that is modified by acquired constituents post secretion. This distinguishes EVs from synthetic nanoparticulate biomaterials that are limited to an adsorption-based, acquired biocorona. The EV biocorona molecular constituents were radiolabeled with 125I to study biocorona constituents and its surface dynamics. As example toolset applications, 125I-EVs were utilized to study EV cell trafficking and the stability of the EV biocorona during storage. The biocorona of EVs consisted of proteins, lipids, DNA and RNA. The cellular uptake of 125I-EVs was temperature dependent and internalized 125I-EVs were rapidly recycled by cells. When 125I-EVs were stored in a purified state, they exhibited time and temperature dependent biocorona shedding and proteolytic degradation that was partially inhibited in the presence of serum. The EV biocorona is complex and dynamic. Radiolabeling of the EV biocorona enables a unique platform methodology to study the biocorona and will facilitate unlocking EV's full clinical translation potential. The EV biocorona affects EV mediated biological processes in health and disease. Acquiring knowledge of the EV biocorona composition, dynamics, stability and structure not only informs the diagnostic and therapeutic translation of EVs but also aids in designing biomimetic nanomaterials for drug delivery. [Display omitted] • The extracellular vesicle (EV) has a complex 'biocorona' that consists of proteins, lipids, DNA and RNA. • Nucleic acids in the EV biocorona are both membrane protein bound and non-protein bound. • The biocorona exhibits time and temperature dependent proteolytic shedding and degradation. • Cell trafficking of EVs includes rapid recycling of internalized EVs. [ABSTRACT FROM AUTHOR]

In this work, the toxicity and biodistribution of graphene oxide (GO) and oxidized multi-walled carbon nanotubes (MWCNT) were investigated in Caenorhabditis elegans. Bovine serum albumin (BSA) was selected as a model protein to evaluate the influence of protein corona formation on materials physicochemical properties, colloidal stability, and toxicity. Biological assays were performed to assess the effects of bare and albumin corona coated materials on survival, oxidative stress, intestinal barrier permeability, growth, reproduction, and fertility. Critical alterations in topography, surface roughness and chemistry of GO and MWCNT were observed due to albumin corona formation. These modifications were associated with changes in colloidal stability of materials and prevention of their aggregation and sedimentation in nematode testing medium. Both GO and MWCNT caused damage to nematode survival, growth, reproduction, and fertility, as well as enhanced oxidative stress and permeability of the intestinal barrier. But GO was more toxic than MWCNT to C. elegans, especially at long-term assays. Albumin corona mitigated 100% of acute and chronic effects of MWCNT. In contrast, the negative effects of GO were not completely mitigated; GO inhibited 16.2% of nematode growth, 86.5% of reproduction, and 32.0% of fertility at the highest concentration evaluated (10 mg L -1 ), while corona coated GO mitigated 50% and 100% of fertility and growth, respectively. Confocal Raman spectroscopy imaging was crucial to point out that bare and albumin corona coated GO and MWCNT crossed the C. elegans intestinal barrier reaching its reproductive organs. However, BSA corona protected the nematodes targeted organs from negative effects from MWCNT and blocked its translocation to other tissues, while coated GO was translocated inside the nematode affecting the functionality of crucial organs. In addition, coated MWCNT was excreted after 2 h of food resumption, whereas coated GO still accumulated in the nematode intestine. Our results demonstrate that the materials different translocation and excretion patterns in C. elegans had a relation to the impaired physiological functions of primary and secondary organs. This work is a contribution towards a better understanding of the impacts of protein corona on the toxicity of graphene oxide and carbon nanotubes; essential information for biological applications and nanosafety., (Copyright © 2022. Published by Elsevier B.V.)

Nanomaterials offer promising solutions as drug delivery systems and imaging agents in response to the demand for better therapeutics and diagnostics. However, the limited understanding of the interaction between nanoparticles and biological entities is currently hampering the development of new systems and their applications in clinical settings. Proteins and lipids in biological fluids are known to complex with nanoparticles to form a "biomolecular corona". This has been shown to affect particles' morphology and behavior in biological systems and their interactions with cells. Hence, understanding how nanomaterials' physicochemical properties affect the formation and composition of this biocorona is a crucial step. This work evaluates existing literature on how morphology (size and shape), and surface chemistry (charge and hydrophobicity) of nanoparticles influence the formation of protein corona. The latest evidence suggest that although surface charge promotes the interaction with proteins and lipids, surface chemistry plays a leading role in determining the affinity of the nanoparticle for biomolecules and, ultimately, the composition of the corona. More recently the study of additional nanoparticles' properties like shape and surface chirality have demonstrated a significant effect on protein corona architecture, providing new tools to tailor biomolecular corona formation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials., (© 2022 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

As nanoparticles have been found to cause a range of harmful impacts in biota, understanding processes and transformations which may stabilize and increase their persistence time in the environment are of great importance. As nanoparticles carried in riverine or wastewaters will eventually reach estuaries, understanding their behavior and transport potential in this transition zone from fresh to marine waters is essential, particularly as estuaries are sensitive ecological zones, oftentimes encompassing ornithologically important areas. In this direction, we report on the influence of combined gradients of riverine and marine natural organic matter (NOM) on the temporal stability of biocorona-encapsulated silver nanoparticles in terms of ion release kinetics. In parallel, salinity, pH and oxygen saturation were simultaneously varied to create a model to mimic the complex estuarine environment. While humic acid (HA) and alginate (Alg) disrupted the stabilizing ability of the nanoparticle protein corona to a greater and lesser degree, respectively, they slowed the rate of ion release in freshwater at pH 6.6 and in saltwater at pH 8, respectively, while oxygen saturation was also found to be an important factor. Thus, as the type of NOM changes with pH along a salinity gradient in an estuary, conditions required to increase the persistence time of nanoparticles are serendipitously met, with greater colloidal stability achieved in cases where there is more rapid replacement of HA with Alg. Despite the strong gradients in ionic strength, pH and oxygen saturation, the protein corona was not sufficiently disrupted at the nanoparticle surface to be substituted by NOM indicating the greater adsorption energy of the protein's hydrophobic domains. Ultimately, it is the specific NOM profile of individual estuaries that may provide the best indicator for predicting the stability and persistence of silver nanoparticles as they transition from fresh to salt water environments. [ABSTRACT FROM AUTHOR]

Climate change and population growth are straining agricultural output. To counter these changes and meet the growing demand for food and energy, the monitoring and engineering of crops are becoming increasingly necessary. Nanoparticle-based sensors have emerged in recent years as new tools to advance agricultural practices. As these nanoparticle-based sensors enter and travel through the complex biofluids within plants, biomolecules including proteins, metabolites, lipids, and carbohydrates adsorb onto the nanoparticle surfaces, forming a coating known as the "bio-corona". Understanding these nanoparticle-biomolecule interactions that govern nanosensor function in plants will be essential to successfully develop and translate nanoparticle-based sensors into broader agricultural practice.

Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA–lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery. [ABSTRACT FROM AUTHOR]

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.

Two different types of nanoparticles (silicon dioxide and titanium dioxide) were selected within this study in order to analyze the interaction with bovine and human serum albumin. These particles were characterized by transmission and scanning electron microscopy (TEM and SEM), X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDXS). In addition, the hydrodynamic size and the zeta potential were measured for all these nanoparticles. The serum proteins were incubated with the nanoparticles for up to one hour, and the albumin adsorption on the particle surface was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The effect induced on the secondary structure of proteins was analyzed by Fourier transform infrared spectroscopy (FTIR). The results showed that albumin adsorbed on the surface of both types of nanoparticles, but in different quantities. In addition, we noticed different changes in the structure of albumin depending on the physicochemical properties of each type of particle tested. In conclusion, our study provides a comparative analysis between the different characteristics of nanoparticles and the protein corona formed on the particle surface and effects induced on protein structure in order to direct the development of "safe-by-design" nanoparticles, as their demands for research and applications continue to increase. [ABSTRACT FROM AUTHOR]