Enhanced competitive protein exchange at the nano-bio interface enables ultra-deep coverage of the human plasma proteome

We have developed a scalable system that leverages protein nano interactions to overcome current limitations of deep plasma proteomics in large cohorts. Introducing proprietary engineered nanoparticles (NPs) into a biofluid such as blood plasma leads to the formation of a selective and reproducible protein corona at the particle protein interface, driven by the relationship between protein-NP affinity and protein abundance. Here we demonstrate the importance of tuning the protein to NP surface ratio (P/NP), which determines the competition between proteins for binding. We demonstrate how optimized P/NP ratio affects protein corona composition, ultimately enhancing performance of a fully automated NP based deep proteomic workflow (Proteograph). By limiting the available binding surface of NPs and increasing the binding competition, we identify 1.2 to 1.7x more proteins with only 1% false discovery rate on the surface of each NP, and up to 3x compared to a standard neat plasma proteomics workflow. Moreover, increased competition means proteins are more consistently identified and quantified across replicates, yielding precise quantification and improved coverage of the plasma proteome when using multiple physicochemically distinct NPs. In summary, by optimizing NPs and assay conditions, we capture a larger and more diverse set of proteins, enabling deep proteomic studies at scale.

Biomedical Applications of Nanoparticles

In recent years, there has been significant growth and burgeoning interest in utilizing nanoparticles for various biomedical applications, including medical diagnostics, targeted drug delivery, tissue engineering, regenerative medicine, and biomedical textiles. In particular, nanoparticles functionalized with biological molecules have unique properties and are very effective in medical diagnostics. Besides that, nanoparticles have a wide range of therapeutic applications, including the development of nanodrug delivery systems, the design of novel drugs, as well as their contribution to the design of therapeutic materials. This chapter provides an overview of recent advancements in the biomedical applications of nanoparticles. Finally, this chapter discusses the challenges of the toxicological evaluation of engineered nanoparticles and the importance of conducting detailed studies on the synthesis of future nanomaterials to develop cutting-edge technologies for addressing a wide range of biomedical issues.

Using the Isalos platform to develop a (Q)SAR model that predicts metal oxide toxicity utilizing facet-based electronic, image analysis-based, and periodic table derived properties as descriptors

Engineered nanoparticles (NPs) are being studied for their potential to harm humans and the environment. Biological activity, toxicity, physicochemical properties, fate, and transport of NPs must all be evaluated and/or predicted. In this work, we explored the influence of metal oxide nanoparticle facets on their toxicity towards bronchial epithelial (BEAS-2B), Murine myeloid (RAW 264.7), and E. coli cell lines. To estimate the toxicity of metal oxide nanoparticles grown to a low facet index, a quantitative structure–activity relationship ((Q)SAR) approach was used. The novel model employs theoretical (density functional theory calculations) and experimental studies (transmission electron microscopy images from which several particle descriptors are extracted and toxicity data extracted from the literature) to investigate the properties of faceted metal oxides, which are then utilized to construct a toxicity model. The classification mode of the k-nearest neighbour algorithm (EnaloskNN, Enalos Chem/Nanoinformatics) was used to create the presented model for metal oxide cytotoxicity. Four descriptors were identified as significant: core size, chemical potential, enthalpy of formation, and electronegativity count of metal oxides. The relationship between these descriptors and metal oxide facets is discussed to provide insights into the relative toxicities of the nanoparticle. The model and the underpinning dataset are freely available on the NanoSolveIT project cloud platform and the NanoPharos database, respectively.

Engineered nanomaterials induce alterations in biological barriers: focus on paracellular permeability

Engineered nanoparticles (ENPs) are widely used in medical diagnosis and treatment, as food additives and as energy materials. ENPs may exert adverse or beneficial effects on the human body, which may be linked to interactions with biological barriers. In this review, the authors summarize the influences of four typical metal/metal oxide nanomaterials (Ag, TiO2, Au, ZnO nanoparticles) on the paracellular permeability of biological barriers. Disruptions on tight junctions, adhesion junctions, gap junctions and desmosomes via complex signaling pathways, such as the MAPK, PKC and ROCK signaling pathways, affect paracellular permeability. Reactive oxygen species and cytokines underlie the mechanism of ENP-triggered alterations in paracellular permeability. This review provides the information necessary for the cautious application of nanoparticles in medicine and life sciences in the future.

In Vitro Toxicity of Industrially Relevant Engineered Nanoparticles in Human Alveolar Epithelial Cells: Air–Liquid Interface versus Submerged Cultures

Diverse industries have already incorporated within their production processes engineered nanoparticles (ENP), increasing the potential risk of worker inhalation exposure. In vitro models have been widely used to investigate ENP toxicity. Air–liquid interface (ALI) cell cultures have been emerging as a valuable alternative to submerged cultures as they are more representative of the inhalation exposure to airborne nano-sized particles. We compared the in vitro toxicity of four ENP used as raw materials in the advanced ceramics sector in human alveolar epithelial-like cells cultured under submerged or ALI conditions. Submerged cultures were exposed to ENP liquid suspensions or to aerosolised ENP at ALI. Toxicity was assessed by determining LDH release, WST-1 metabolisation and DNA damage. Overall, cells were more sensitive to ENP cytotoxic effects when cultured and exposed under ALI. No significant cytotoxicity was observed after 24 h exposure to ENP liquid suspensions, although aerosolised ENP clearly affected cell viability and LDH release. In general, all ENP increased primary DNA damage regardless of the exposure mode, where an increase in DNA strand-breaks was only detected under submerged conditions. Our data show that at relevant occupational concentrations, the selected ENP exert mild toxicity to alveolar epithelial cells and exposure at ALI might be the most suitable choice when assessing ENP toxicity in respiratory models under realistic exposure conditions.

Interactions of Coated-Gold Engineered Nanoparticles with Aquatic Higher Plant Salvinia minima Baker

The study investigated the interactions of coated-gold engineered nanoparticles (nAu) with the aquatic higher plant Salvinia minima Baker in 2,7, and 14 d. Herein, the nAu concentration of 1000 µg/L was used; as in lower concentrations, analytical limitations persisted but >1000 µg/L were deemed too high and unlikely to be present in the environment. Exposure of S. minima to 1000 µg/L of citrate (cit)- and branched polyethyleneimine (BPEI)-coated nAu (5, 20, and 40 nm) in 10% Hoagland’s medium (10 HM) had marginal effect on biomass and growth rate irrespective of nAu size, coating type, or exposure duration. Further, results demonstrated that nAu were adsorbed on the plants’ roots irrespective of their size or coating variant; however, no evidence of internalization was apparent, and this was attributed to high agglomeration of nAu in 10 HM. Hence, adsorption was concluded as the basic mechanism of nAu accumulation by S. minima. Overall, the long-term exposure of S. minima to nAu did not inhibit plant biomass and growth rate but agglomerates on plant roots may block cell wall pores, and, in turn, alter uptake of essential macronutrients in plants, thus potentially affecting the overall ecological function.

Field Application of ZnO and TiO2 Nanoparticles on Agricultural Plants

Engineered nanoparticles (ENPs) have potential application in precision farming and sustainable agriculture. Studies have shown that ENPs enhance the efficiency of the delivery of agrochemicals and thus, have the potential to positively affect the environment, thereby improving the growth and health of the crops. However, the majority of the research on the effects of ENPs on plants and in agricultural applications have been limited to controlled laboratory conditions. These conditions do not fully consider various aspects inherent to the growth of agricultural plants in fields under changing weather and climate. Some of the most investigated ENPs in the agricultural research area are ZnO nanoparticles (ZnO NPs) and TiO2 nanoparticles (TiO2 NPs). ZnO NPs have the potential to increase crop production and stress resistance, mainly by the slow release of Zn ions to crops. Unlike ZnO NPs, TiO2 NPs have less well-understood means of action, and are generally considered as plant growth promoter. This mini review presents information compiled for ZnO and TiO2 NPs, their influence on agricultural plants with emphasis on particularly effect on plant growth, nutrient distribution and pollution remediation under field conditions. It is concluded that in order to gain a broader perspective, more field studies are needed, particularly multigeneration studies, to fully understand the effects of the ENPs on agricultural plants’ growth and improvement of their health.

Innate Memory Reprogramming by Gold Nanoparticles Depends on the Microbial Agents That Induce Memory

Innate immune memory, the ability of innate cells to react in a more protective way to secondary challenges, is induced by exposure to infectious and other exogeous and endogenous agents. Engineered nanoparticles are particulate exogenous agents that, as such, could trigger an inflammatory reaction in monocytes and macrophages and could therefore be also able to induce innate memory. Here, we have evaluated the capacity of engineered gold nanoparticles (AuNPs) to induce a memory response or to modulate the memory responses induced by microbial agents. Microbial agents used were in soluble vs. particulate form (MDP and the gram-positive bacteria Staphylococcus aureus; β-glucan and the β-glucan-producing fungi C. albicans), and as whole microrganisms that were either killed (S. aureus, C. albicans) or viable (the gram-negative bacteria Helicobacter pylori). The memory response was assessed in vitro, by exposing human primary monocytes from 2-7 individual donors to microbial agents with or without AuNPs (primary response), then resting them for 6 days to allow return to baseline, and eventually challenging them with LPS (secondary memory response). Primary and memory responses were tested as production of the innate/inflammatory cytokine TNFα and other inflammatory and anti-inflammatory factors. While inactive on the response induced by soluble microbial stimuli (muramyl dipeptide -MDP-, β-glucan), AuNPs partially reduced the primary response induced by whole microorganisms. AuNPs were also unable to directly induce a memory response but could modulate stimulus-induced memory in a circumscribed fashion, limited to some agents and some cytokines. Thus, the MDP-induced tolerance in terms of TNFα production was further exacerbated by co-priming with AuNPs, resulting in a less inflammatory memory response. Conversely, the H. pylori-induced tolerance was downregulated by AuNPs only relative to the anti-inflammatory cytokine IL-10, which would lead to an overall more inflammatory memory response. These effects of AuNPs may depend on a differential interaction/association between the reactive particle surfaces and the microbial components and agents, which may lead to a change in the exposure profiles. As a general observation, however, the donor-to-donor variability in memory response profiles and reactivity to AuNPs was substantial, suggesting that innate memory depends on the individual history of exposures.