Milk Protein Adsorption on Metallic Iron Surfaces.

Food processing and consumption involves multiple contacts between biological fluids and solid materials of processing devices, of which steel is one of the most common. Due to the complexity of these interactions, it is difficult to identify the main control factors in the formation of undesirable deposits on the device surfaces that may affect safety and efficiency of the processes. Mechanistic understanding of biomolecule-metal interactions involving food proteins could improve management of these pertinent industrial processes and consumer safety in the food industry and beyond. In this work, we perform a multiscale study of the formation of protein corona on iron surfaces and nanoparticles in contact with cow milk proteins. By calculating the binding energies of proteins with the substrate, we quantify the adsorption strength and rank proteins by the adsorption affinity. We use a multiscale method involving all-atom and coarse-grained simulations based on generated ab initio three-dimensional structures of milk proteins for this purpose. Finally, using the adsorption energy results, we predict the composition of protein corona on iron curved and flat surfaces via a competitive adsorption model.

Fabrication of polydimethylsiloxane-attached solid slippery surface with high underwater transparency towards the antifouling of optical window for marine instruments.

Marine optical instruments are commonly suffering serious biofouling problem caused by the adhesion of marine microorganisms, which severely affects the instruments to monitor the marine environment. Herein, we developed a robust solid slippery surface (SSS) by fabricated a covalently attached polydimethylsiloxane (PDMS) layer on glass substrate to solve the biofouling problem of marine optical instrument windows. The SSS could effectively inhibit the settlements of marine microorganism (bacteria and alga) in various environmental conditions, resulting from the high flexibility of PDMS molecular chains, and thus could maintain its high underwater-transparency. The antifouling mechanism of SSS was results from the weak nonspecific electrostatic Lifshitz-van der Waals forces and less specific hydrogen bonds between SSS and microorganism, which was been confirmed via both single bacterial force spectroscopy measurement and molecular dynamics simulation. Compared with the traditional slippery lubricant-infused porous surface (SLIPS), the SSS exhibited a better robust mechanical stability than that of the SLIPS. In addition, our study provides a valuable method to fabricated the SSS with reliable underwater-transmittance and antifouling properties, which is promised for the applications for the antifouling of marine optical instruments.

Virus-Mimicking Polymer Nanoparticles Targeting CD169+ Macrophages as Long-Acting Nanocarriers for Combination Antiretrovirals.

Monosialodihexosylganglioside (GM3)-presenting lipid-coated polymer nanoparticles (NPs) that recapitulate the sequestration of human immunodeficiency virus-1 (HIV-1) particles in CD169+ virus-containing compartments (VCCs) of macrophages were developed as carriers for delivery and sustained release of a combination of two antiretrovirals (ARVs), rilpivirine (RPV) and cabotegravir (CAB). RPV and CAB were co-loaded into GM3-presenting lipid-coated polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA) NPs without loss in potency of the drugs. GM3-presenting PLA NPs demonstrated the most favorable release properties and achieved inhibition of HIV-1 infection of primary human macrophages for up to 35 days. Intracellular localization of GM3-presenting PLA NPs in VCCs correlated with retention of intracellular ARV concentrations and sustained inhibition of HIV-1 infection. This work elucidates the design criteria of lipid-coated polymer NPs to utilize CD169+ macrophages as cellular drug depots for eradicating the viral reservoir sites or to achieve long-acting prophylaxis against HIV-1 infection.

Methods, models, mechanisms and metadata: Introducing the Nanotoxicology collection at F1000Research.

Nanotoxicology is a relatively new field of research concerning the study and application of nanomaterials to evaluate the potential for harmful effects in parallel with the development of applications. Nanotoxicology as a field spans materials synthesis and characterisation, assessment of fate and behaviour, exposure science, toxicology / ecotoxicology, molecular biology and toxicogenomics, epidemiology, safe and sustainable by design approaches, and chemoinformatics and nanoinformatics, thus requiring scientists to work collaboratively, often outside their core expertise area. This interdisciplinarity can lead to challenges in terms of interpretation and reporting, and calls for a platform for sharing of best-practice in nanotoxicology research. The F1000Research Nanotoxicology collection, introduced via this editorial, will provide a place to share accumulated best practice, via original research reports including no-effects studies, protocols and methods papers, software reports and living systematic reviews, which can be updated as new knowledge emerges or as the domain of applicability of the method, model or software is expanded. This editorial introduces the Nanotoxicology Collection in F1000Research. The aim of the collection is to provide an open access platform for nanotoxicology researchers, to support an improved culture of data sharing and documentation of evolving protocols, biological and computational models, software tools and datasets, that can be applied and built upon to develop predictive models and move towards in silico nanotoxicology and nanoinformatics. Submissions will be assessed for fit to the collection and subjected to the F1000Research open peer review process.

Construction of Bio-Nano Interfaces on Nanozymes for Bioanalysis.

Nanomaterials with enzyme-like activity (nanozymes) have been of great interest in broad applications ranging from biosensing to biomedical applications. Despite that much effort has been devoted to the development of the synthesis and applications of nanozymes, it is essential to understand the interactions between nanozymes and most commonly used biomolecules, i.e., avidin, streptavidin (SA), bovine serum albumin (BSA), immunoglobulin G (IgG), and glutathione (GSH), yet they have been rarely explored. Here, a series of bio-nano interfaces were constructed through direct immobilization of proteins on a variety of iron oxide and carbon-based nanozymes with different dimensions, including Fe3O4 nanoparticles (NPs, 0D), Fe3O4@C NPs (0D), Fe3O4@C nanowires (NWs, 1D), and graphene oxide nanosheets (GO NSs, 2D). Such interfaces enabled the modulation of the catalytic activities of the nanozymes with varying degrees, which allowed a good identification of multiplex proteins with high accuracy. Given the maximum inhibition on Fe3O4@C NP by BSA, we established molecular switches based on aptamer and toehold DNA, as well as Boolean logic gates (AND and NOR) in response to both DNA and proteins. Also importantly, we developed an on-particle reaction strategy for colorimetric detection of GSH with ultrahigh sensitivity and good specificity. The proposed sensor achieved a broad dynamic range spanning 7 orders of magnitude with a detection limit down to 200 pg mL-1, which was better than that of an in-solution reaction-based biosensor by 2 orders of magnitude. Furthermore, we explored the mechanisms of the interactions at bio-nano interfaces by studying the interfacial factors, including surface coverage, salt concentration, and the curvature of the nanozyme. This study offered new opportunities in the elaborate design and better utilization of nanozymes for bioanalysis in clinical diagnosis and in vivo detection.

Bio-nano interactions: binding proteins, polysaccharides, lipids and nucleic acids onto magnetic nanoparticles.

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.

In Silico Prediction of Protein Adsorption Energy on Titanium Dioxide and Gold Nanoparticles.

The free energy of adsorption of proteins onto nanoparticles offers an insight into the biological activity of these particles in the body, but calculating these energies is challenging at the atomistic resolution. In addition, structural information of the proteins may not be readily available. In this work, we demonstrate how information about adsorption affinity of proteins onto nanoparticles can be obtained from first principles with minimum experimental input. We use a multiscale model of protein-nanoparticle interaction to evaluate adsorption energies for a set of 59 human blood serum proteins on gold and titanium dioxide (anatase) nanoparticles of various sizes. For each protein, we compare the results for 3D structures derived from experiments to those predicted computationally from amino acid sequences using the I-TASSER methodology and software. Based on these calculations and 2D and 3D protein descriptors, we develop statistical models for predicting the binding energy of proteins, enabling the rapid characterization of the affinity of nanoparticles to a wide range of proteins.

Nanoscale surface curvature modulates nanoparticle-protein interactions.

Rational optimization of nanoparticle (NP) surfaces is essential for successful conjugation of proteins to NPs for numerous applications. Using surface-roughened NPs (SRNPs) and quasi-spherical NPs (QSNPs) as two model nanostructures, we examined the effects of local surface curvature on protein conformation and interfacial behaviors by circular dichroism (CD) spectroscopy, fluorescence emission spectroscopy (FES), and isothermal titration calorimetry (ITC). The surface of SRNPs consisted of a mixture of undercoordinated and close-packed surface atoms at the highly curved and locally flat surface regions, respectively, whereas QSNPs were primarily enclosed by {100} and {111} facets covered with close-packed surface atoms. Our findings demonstrated that: 1) SRNPs possess higher tendency to denature BSA and accommodate a higher number of BSA molecules on the surface and 2) the aggregation of AuNP-BSA complexes, likely induced by either denatured BSA or reduced electrostatic repulsion between complexes, is dependent on both the BSA concentration and the NP surface curvature. This study also indicated that NP local surface curvature could potentially be used as a design strategy to preserve the biological function of proteins.

Nanomaterials in the Environment Acquire an "Eco-Corona" Impacting their Toxicity to Daphnia Magna-a Call for Updating Toxicity Testing Policies.

Nanomaterials (NMs) are particles with at least one dimension between 1 and 100 nm and a large surface area to volume ratio, providing them with exceptional qualities that are exploited in a variety of industrial fields. Deposition of NMs into environmental waters during or after use leads to the adsorption of an ecological (eco-) corona, whereby a layer of natural biomolecules coats the NM changing its stability, identity and ultimately toxicity. The eco-corona is not currently incorporated into ecotoxicity tests, although it has been shown to alter the interactions of NMs with organisms such as Daphnia magna (D. magna). Here, the literature on environmental biomolecule interactions with NMs is synthesized and a framework for understanding the eco-corona composition and its role in modulating NMs ecotoxicity is presented, utilizing D. magna as a model. The importance of including biomolecules as part of the current international efforts to update the standard testing protocols for NMs, is highlighted. Facilitating the formation of an eco-corona prior to NMs ecotoxicity testing will ensure that signaling pathways perturbed by the NMs are real rather than being associated with the damage arising from reactive NM surfaces "acquiring" a corona by pulling biomolecules from the organism's surface.

Protein corona variation in nanoparticles revisited: A dynamic grouping strategy.

Bio-nano interface investigation models are mainly based on the type of proteins present on corona, bio-nano interaction responses and the evaluation of final outcomes. Due to the extensive diversity in correlative models for investigation of nanoparticles biological responses, a comprehensive model considering different aspects of bio-nano interface from nanoparticles properties to protein corona fingerprints appeared to be essential and cannot be ignored. In order to minimize divergence in studies in the era of bio-nano interface and protein corona with following therapeutic implications, a useful investigation model on the basis of RADAR concept is suggested. The contents of RADAR concept consist of five modules: 1- Reshape of our strategy for synthesis of nanoparticles (NPs), 2- Application of NPs selected based on human fluid, 3- Delivery strategy of NPs selected based on target tissue, 4- Analysis of proteins present on corona using correct procedures and 5- Risk assessment and risk reduction upon the collection and analysis of results to increase drug delivery efficiency and drug efficacy. RADAR grouping strategy for revisiting protein corona phenomenon as a key of success will be discussed with respect to the current state of knowledge.

Bioelectricity, Its Fundamentals, Characterization Methodology, and Applications in Nano-Bioprobing and Cancer Diagnosis.

Bioelectricity is an essential characteristic of a biological system that has played an important role in medical diagnosis particularly in cancer liquid biopsy. However, its biophysical origin and measurements have presented great challenges in experimental methodologies. For instance, in dynamic cell processes, bioelectricity cannot be accurately determined as a static electrical potential via electrophoresis. Cancer cells fundamentally differ from normal cells by having a much higher rate of glycolysis resulting in net negative charges on cell surfaces. The most recent investigations on cancer cell surface charge that is the direct bio-electrical manifestation of the "Warburg Effect," which can be directly monitored by specially designed nanoprobes, has been provided. The most up-to-date research results from charge-mediated cell targeting are reviewed. Correlations between the cell surface charge and cancer cell metabolism are established based on cell/probe electrostatic interactions. Bioelectricity is utilized not only as an analyte for investigation of the metabolic state of the cancer cells, but also applied in electrostatically and magnetically capturing of the circulating tumor cells from whole blood. Also reviewed is on the isolation of Candida albicans via bioelectricity-driven nanoparticle binding on fungus with surface charges.

Translating Current Bioanalytical Techniques for Studying Corona Activity.

The recent discovery of the biological corona is revolutionising our understanding of the in vivo behaviour of nanomaterials. Accurate analysis of corona bioactivity is essential for predicting the fate of nanomaterials and thereby improving nanomedicine design. Nevertheless, current biotechniques for protein analysis are not readily adaptable for analysing corona proteins, given that their conformation, activity, and interaction may largely differ from those of the native proteins. Here, we introduce and propose tailor-made modifications to five types of mainstream bioanalytical methodologies. We specifically illustrate how these modifications can translate existing techniques for protein analysis into competent tools for dissecting the composition, bioactivity, and interaction (with both nanomaterials and the tissue) of corona formed on specific nanomaterial surfaces.

Current Application of Capillary Electrophoresis in Nanomaterial Characterisation and Its Potential to Characterise the Protein and Small Molecule Corona.

Due to the increasing use and production of nanomaterials (NMs), the ability to characterise their physical/chemical properties quickly and reliably has never been so important. Proper characterisation allows a thorough understanding of the material and its stability, and is critical to establishing dose-response curves to ascertain risks to human and environmental health. Traditionally, methods such as Transmission Electron Microscopy (TEM), Field Flow Fractionation (FFF) and Dynamic Light Scattering (DLS) have been favoured for size characterisation, due to their wide-availability and well-established protocols. Capillary Electrophoresis (CE) offers a faster and more cost-effective solution for complex dispersions including polydisperse or non-spherical NMs. CE has been used to rapidly separate NMs of varying sizes, shapes, surface modifications and compositions. This review will discuss the literature surrounding the CE separation techniques, detection and NM characteristics used for the analysis of a wide range of NMs. The potential of combining CE with mass spectrometry (CE-MS) will also be explored to further expand the characterisation of NMs, including the layer of biomolecules adsorbed to the surface of NMs in biological or environmental compartments, termed the acquired biomolecule corona. CE offers the opportunity to uncover new/poorly characterised low abundance and polar protein classes due to the high ionisation efficiency of CE-MS. Furthermore, the possibility of using CE-MS to characterise the poorly researched small molecule interactions within the NM corona is discussed.

In-vitro in-vivo correlation (IVIVC) in nanomedicine: Is protein corona the missing link?

One of the unmet challenges in nanotechnology is to understand and establish the relationship between physicochemical properties of nanoparticles (NPs) and its biological interactions (bio-nano interactions). However, we are still far from assessing the biofate of NPs in a clear and unquestionable manner. Recent developments in the area of bio-nano interface and the understanding of protein corona (PC) has brought new insight in predicting biological interactions of NPs. PC refers to the spontaneous formation of an adsorbed layer of biomolecules on the surface of NPs in a biological environment. PC formation involves the spatiotemporal interplay of an intricate network of biological, environmental and particle characteristics. NPs with its PC can be viewed as a biological entity, which interacts with cells and barriers in a biological system. Recent studies on the bio-nano interface have revealed biological signatures that participate in cellular and physiological bioprocesses and control the biofate and toxicity of NPs. The ability of in-vitro derived parameters to forecast in-vivo consequences by developing a mathematical model forms the basis of in-vitro in-vivo correlation (IVIVC). Understanding the effect of bio-nano interactions on the biological consequences of NPs at the cellular and physiological level can have a direct impact on the translation of future nanomedicines and can lead to the ultimate goal of developing a mathematical IVIVC model. The review summarizes the emerging paradigms in the field of bio-nano-interface which clearly suggests an urgent need to revisit existing protocols in nanotechnology for defining the physicochemical correlates of bio-nano interactions.

Bio-nano interface and environment: A critical review.

The bio-nano interface is the boundary where engineered nanomaterials (ENMs) meet the biological system, exerting the biological function for which they have been designed or inducing adverse effects on other cells or organisms when they reach nontarget scenarios (i.e., the natural environment). Research has been performed to determine the fate, transport, and toxic properties of ENMs, but much of it is focused on pristine or so-called as-manufactured ENMs, or else modifications of the materials were not assessed. We review the most recent progress regarding the bio-nano interface and the transformations that ENMs undergo in the environment, paying special attention to the adsorption of environmental biomolecules on the surface of ENMs. Whereas the protein corona has received considerable attention in the fields of biomedics and human toxicology, its environmental analogue (the eco-corona) has been much less studied. A section dedicated to the analytical methods for studying and characterizing the eco-corona is also presented. We conclude by presenting and discussing the key problems and knowledge gaps that need to be resolved in the near future regarding the bio-nano interface and the eco-corona. Environ Toxicol Chem 2017;36:3181-3193. © 2017 SETAC.

Exploiting the novel properties of protein coronas: emerging applications in nanomedicine.

Protein coronas have been the focus of a great deal of study recently due to their inevitable formation and their impact on the biological consequences of nanomaterials. Although the field is still far from completely and definitively understanding protein coronas, we now have a good understanding of their behavior and their key characteristics. Protein corona composition changes with the environment and time, and also the physical properties of the underlying nanoparticle. More importantly, the protein corona has significant biological impact. Because we have a basic understanding of coronas, we can now move forward to exploiting their unique properties. Here, we discuss some emerging ways in which the protein corona is explicitly utilized for different applications in biology and medicine.

Merging worlds of nanomaterials and biological environment: factors governing protein corona formation on nanoparticles and its biological consequences.

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.

'Bio-nano interactions: new tools, insights and impacts': summary of the Royal Society discussion meeting.

Bio-nano interactions can be defined as the study of interactions between nanoscale entities and biological systems such as, but not limited to, peptides, proteins, lipids, DNA and other biomolecules, cells and cellular receptors and organisms including humans. Studying bio-nano interactions is particularly useful for understanding engineered materials that have at least one dimension in the nanoscale. Such materials may consist of discrete particles or nanostructured surfaces. Much of biology functions at the nanoscale; therefore, our ability to manipulate materials such that they are taken up at the nanoscale, and engage biological machinery in a designed and purposeful manner, opens new vistas for more efficient diagnostics, therapeutics (treatments) and tissue regeneration, so-called nanomedicine. Additionally, this ability of nanomaterials to interact with and be taken up by cells allows nanomaterials to be used as probes and tools to advance our understanding of cellular functioning. Yet, as a new technology, assessment of the safety of nanomaterials, and the applicability of existing regulatory frameworks for nanomaterials must be investigated in parallel with development of novel applications. The Royal Society meeting 'Bio-nano interactions: new tools, insights and impacts' provided an important platform for open dialogue on the current state of knowledge on these issues, bringing together scientists, industry, regulatory and legal experts to concretize existing discourse in science law and policy. This paper summarizes these discussions and the insights that emerged.

Inorganic Nanoparticles for Therapeutic Delivery: Trials, Tribulations and Promise.

Inorganic nanomaterials have a wide array of physical and structural properties that make them attractive candidates for imaging and therapeutic delivery. Nanoparticle platforms have been intensely studied for these applications, and examples are starting to enter the clinic. This review looks at why inorganic particles provide promising platforms for biomedicine, and what issues need to be addressed for them to reach their potential.

25th anniversary article: semiconductor nanowires--synthesis, characterization, and applications.

Semiconductor nanowires (NWs) have been studied extensively for over two decades for their novel electronic, photonic, thermal, electrochemical and mechanical properties. This comprehensive review article summarizes major advances in the synthesis, characterization, and application of these materials in the past decade. Developments in the understanding of the fundamental principles of "bottom-up" growth mechanisms are presented, with an emphasis on rational control of the morphology, stoichiometry, and crystal structure of the materials. This is followed by a discussion of the application of nanowires in i) electronic, ii) sensor, iii) photonic, iv) thermoelectric, v) photovoltaic, vi) photoelectrochemical, vii) battery, viii) mechanical, and ix) biological applications. Throughout the discussion, a detailed explanation of the unique properties associated with the one-dimensional nanowire geometry will be presented, and the benefits of these properties for the various applications will be highlighted. The review concludes with a brief perspective on future research directions, and remaining barriers which must be overcome for the successful commercial application of these technologies.