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Nanomaterials acquire a biomolecular corona upon introduction to biological media, leading to biological transformations such as changes in protein function, unmasking of epitopes, and protein fibrilization. Ex vivo studies to investigate the effect of nanoparticles on protein-protein interactions are typically performed in buffer and are rarely measured quantitatively in live cells. Here, we measure the differential effect of silica nanoparticles on protein association in vitro vs. in mammalian cells. BtubA and BtubB are a pair of bacterial tubulin proteins identified in Prosthecobacter strains that self-assemble like eukaryotic tubulin, first into dimers and then into microtubules in vitro or in vivo. Förster resonance energy transfer labeling of each of the Btub monomers with a donor (mEGFP) and acceptor (mRuby3) fluorescent protein provides a quantitative tool to measure their binding interactions in the presence of unfunctionalized silica nanoparticles in buffer and in cells using fluorescence spectroscopy and microscopy. We show that silica nanoparticles enhance BtubAB dimerization in buffer due to protein corona formation. However, these nanoparticles have little effect on bacterial tubulin self-assembly in the complex mammalian cellular environment. Thus, the effect of nanomaterials on protein-protein interactions may not be readily translated from the test tube to the cell in the absence of particle surface functionalization that can enable targeted protein-nanoparticle interactions to withstand competitive binding in the nanoparticle corona from other biomolecules. [ABSTRACT FROM AUTHOR]

The in-depth blood-based proteomics is significantly limited owing to the intrinsic wide dynamic range of protein concentrations (over 10 orders of magnitude) and highly abundant proteins (albumin, etc.) in blood. Here, we developed a protein denaturation strategy to enhance the serum proteomic depth via nanoparticle-protein corona for enhanced non-small cell lung cancer (NSCLC) diagnosis. We developed an optimal denaturant panel consists of nature, 30 % acetonitrile, 40 % RapiGest, and 4 M urea respectively treated serum to form various nanoparticle-protein coronas with magnetic nanoparticles (MNPs). Based on this panel, we have identified 1846 proteins by profiling 172 NSCLC serum samples, significantly enhancing the depth of serum proteomics. Furthermore, we selected 15 key proteins with random forest algorithm to distinguish the benign and malignant nodules and achieved an ROC-AUC of 98.44 %. Differentially expressed protein-based pathway analysis revealed that metabolic and immune-related pathways were significantly enriched, in which apolipoproteins play pivotal role in the transfer from benign to malignant nodules. Our study demonstrated a facile serum denaturation strategy for enhanced depth of serum proteomics which will benefit the cancer biomarker discovery and diagnosis. [Display omitted] • An optimal panel consisting of 30 % acetonitrile, 40 % RapiGest, and 4 M urea-denatured serum as well as natural serum resulted 4 different NPCs was developed with MNPs for in-depth serum proteomics. • Based on optimal panel, we identified 1846 proteins by profiling 172 NSCLC clinical serum samples. Fifteen key proteins were selected using a random forest algorithm to distinguish benign and malignant lung nodules (AUC = 98.44 %). • DEPs in benign and malignant nodules were mainly enriched in metabolic and immune-related pathways. Apolipoproteins play a pivotal bridging role in the transition from benign to malignant nodules. • For the first time, we measured the overall serum protein binding affinity to MNPs and found that the binding affinity was decreased upon serum protein denaturation. [ABSTRACT FROM AUTHOR]

In the present report, we focused on the detail study of the optical properties and structural characterization of the Ag NPs for the nanobioconjugate analysis and detection of the conformational structural change of the Hb. The detail optical and structural analysis of Ag NPs has been studied from UV–Vis absorption, emission spectrum, XRD, and HRTEM study. The proteins/Hb are attached immediately onto Ag NPs surface when NPs touch the biological fluids, forming protein corona (PC), which gives their biological identity. The NPs-PC bioconjugate is, more specifically, the true identity of NPs in the physiological world. The adsorption of Hb with Ag NP surfaces has been studied by monitoring the soret band and tryptophan band of Hb. The dynamics of the Hb adsorption on the Ag NPs showed the time constant of surface binding t1 = 5.79 min and 10.23 min and surface reorganization t2 = 500 min and 251.75 min with the use of small and large concentrations of Ag NPs, respectively. The absorption peak shape and size around the wavelength, λ ≈ 406.2 nm of the bioconjugate has been examined by Gaussian and Lorentz curve fitting analysis. The bioconjugate along with the PC formation has been analyzed by HRTEM images and DLS observations. The tertiary deformation of Hb and energy transfer efficiency connecting Ag NPs and Hb are discussed from the emission-quenching phenomenon. The change of the secondary structural elements (α-helix, β-sheets, intermolecular aggregates, intramolecular aggregates) of the bioconjugate has been analyzed from FTIR spectrum. [ABSTRACT FROM AUTHOR]

Iridium oxide (IrOx) is a promising implantable electrode material owing to its remarkable neural stimulation capacity. However, presently, IrOx electrodes lack biocompatibility and bioactive interactions with nerve tissues. Application of polymeric surface coatings results in a weak physical adhesion at the organic/inorganic interface, which limits their wide‐scale application. Herein, a smart iridium oxide‐plasma protein (IrOx‐PP) electrode with enhanced electroactivity, electrochemical stability, cytocompatibility, and bioactivity that can provide controllable topographical, electrical, and chemical stimuli to enhance neuronal activity is proposed. In the inorganic/organic nanoparticle (NP)‐protein corona structures, the soft NP‐corona led to repeated burst‐to‐zero‐to‐burst PP release, while the hard NP‐corona with an ordered atomic structure enhanced the electrochemical stability and bioactivity. The incorporated PP resulted in a higher current storage capacity, lower impedance, better cell growth, and significant neurite outgrowth compared with those obtained with pristine IrOx. The application of electrical stimulation to IrOx‐PP enabled simultaneous neuromodulation, on‐demand PP release, and cell uptake, with a 2‐fold higher cell density and significant neurite outgrowth on IrOx‐PP than on pristine IrOx. This bioactive inorganic‐organic hybrid electrode with the combined features of physical properties and improved neuromodulation is expected to be a revolutionary platform for efficient and biocompatible neural implantation. [ABSTRACT FROM AUTHOR]

The interfacial nano-bio complexion phenomenon provides the enhanced biological response via tagging of the biological moieties on the nanoparticle surface. The dynamic state of the protein-nanoparticle corona makes it suitable for protein quantification, targeting drug delivery and diagnostics applications. Herein, our approach molecular chemistry and optical characteristics of curcumin were used to elucidate the lanthanum carbonate nanospheres (REM 100 ) and proteins interactions. The REM 100 were prepared via novel, mix surfactant assisted homogeneous precipitation route. The spontaneous binding of Casein, Human Serum Albumin (HSA), Lysozyme (LZ) and Bovine Serum Albumin (BSA), Aβ monomer and Aβ aggregates on Curcumin-REM 100 has been observed by protein concentration dependent steady-state fluorescence enhancement of the curcumin. Langmuir protein adsorption model elucidates the maximum surface coverage and an apparent dissociation constant parameter for Casein, Human Serum Albumin (HSA), Lysozyme (LZ) and Bovine Serum Albumin as interacting proteins. The curcumin form a stable hard corona layer over REM 100 surface and accommodates the proteins as soft corona could be possible mechanism observed by steady-state fluorescence anisotropy. Based on all experimental outcomes we demonstrated, curcumin-REM 100 as an efficient fluorescent probe performing compositional quantification of proteins in the nanoparticle-protein corona and able to delineate the monomer and the aggregate state of Amyloid-β with the Limit of detection of 0.2 ±0.045 μM, 30 times more sensitive then Thioflavin T (ThT). The protein-nanoparticle-based methodology optimized were showed great promising feature with its potential to develop as quick and sensitive detection of altered proteins. [ABSTRACT FROM AUTHOR]

The interaction of inorganic nanoparticles and many biological fluids often withstands the formation of a Protein Corona enveloping the nanoparticle. This Protein Corona provides the biological identity to the nanoparticle that the immune system will detect. The formation of this Protein Corona depends not only on the composition of the nanoparticle, its size, shape, surface state and exposure time, but also on the type of media, nanoparticle to protein ratio and the presence of ions and other molecular species that interfere in the interaction between proteins and nanoparticles. This has important implications on immune safety, biocompatibility and the use of nanoparticles in medicine. [ABSTRACT FROM AUTHOR]

Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.

With the potential wide uses of nanoparticles such as carbon nanotubes in biomedical applications, and the growing concerns of nanotoxicity of these engineered nanoparticles, the importance of nanoparticle-protein interactions cannot be stressed enough. In this study, we use both experimental and theoretical approaches, including atomic force microscope images, fluorescence spectroscopy, CD, SDS-PAGE, and molecular dynamics simulations, to investigate the interactions of single-wall carbon nanotubes (SWCNTs) with human serum proteins, and find a competitive binding of these proteins with different adsorption capacity and packing modes. The p-p stacking interactions between SWCNTs and aromatic residues (Trp, Phe, Tyr) are found to play a critical role in determining their adsorption capacity. Additional cellular cytotoxicity assays, with human acute monocytic leukemia cell line and human umbilical vein endothelial cells, reveal that the competitive bindings of blood proteins on the SWCNT surface can greatly alter their cellular interaction pathways and result in much reduced cytotoxicity for these protein-coated SWCNTs, according to their respective adsorption capacity. These findings have shed light toward the design of safe carbon nanotube nanomaterials by comprehensive preconsideration of their interactions with human serum proteins. [ABSTRACT FROM AUTHOR]

Much contemporary nanotoxicology, nanotherapeutic and nanoregulatory research has been characterized by a focus on investigating how delivery of engineered nanoparticles (ENPs) to cells is dictated primarily by components of the ENP surface. An alternative model, some implications of which are discussed here, begins with fundamental physicochemical research into the interaction of a dynamic nanoparticle-protein corona (NPC) with biological systems. The proposed new model also requires, however, that any such fresh NPC physicochemical research approach should involve integration and targeted collaboration from the earliest stages with nanotoxicology, nanotherapeutics and nanoregulatory expertise. The justification for this integrated approach, we argue, relates not just to efficiency and promotion of innovation but to an acknowledgement that public-funded basic physicochemical research in particular should now be accepted to incorporate strong higher order public-goods elements from its inception, not merely after product development at the technology-transfer stage. Issues, such as university-research cooperation, commercialization and intellectual property protection, safety and cost-effectiveness regulatory assessment, as well as technology transfer should not be viewed as second tier considerations, even in a 'blue sky' NPC basic research agenda. [ABSTRACT FROM AUTHOR]