Interactions Of Nanomaterials Research Articles

Metallic Nanoparticles: General Research Approaches to Immunological Characterization.

Our immunity is guaranteed by a complex system that includes specialized cells and active molecules working in a spatially and temporally coordinated manner. Interaction of nanomaterials with the immune system and their potential immunotoxicity are key aspects for an exhaustive biological characterization. Several assays can be used to unravel the immunological features of nanoparticles, each one giving information on specific pathways leading to immune activation or immune suppression. Size, shape, and surface chemistry determine the surrounding corona, mainly formed by soluble proteins, hence, the biological identity of nanoparticles released in cell culture conditions or in a living organism. Here, we review the main laboratory characterization steps and immunological approaches that can be used to understand and predict the responses of the immune system to frequently utilized metallic or metal-containing nanoparticles, in view of their potential uses in diagnostics and selected therapeutic treatments.

Alpha-1-microglobulin/bikunin (AMBP) protein corona (PPC) as biomarker for early diagnosis in non-small-cell lung carcinomas (NSCLC) patients: A case report

Nanoparticles are increasingly used in biomedical applications such as imaging, drug delivery and hyperthermic therapies. The surface of this nanoparticles once incubated with biological medium is covered by proteins constituting a shell named “protein corona”. Thus, understanding the interaction of nanomaterials with biological fluids becomes basic for their application. Recently it has been shown that the protein corona composition is critically affected by biological sample originates from the specific disease. This innovative concept takes the name of “personalized protein corona (PPC)”, which represents a promising strategy for personalized medicine. PPC acts a ‘nano-accumulator’ of proteins with affinity for the particle surface. Thus, this approach allows detecting protein alterations as those produced by clinical manifestations of disease even when they are too small to be detected by rutinary blood tests. Non-small-cell lung carcinomas (NSCLC) is the most common type of lung cancer and it has poor prognosis, because overall survival after 5 years is 20–25% for all stages. Thus, innovative methods for early detection and proper characterization of NSCLC are an urgent task. To this end, we incubated liposomes nanoparticles with plasma from humans with histologically proven NSCLC. In this study we report an NSLC case. We have analyzed the serum before and after incubation with liposome by a HPLC ion trap mass spectrometer. Proteins were identified by fragments characterization of MS/MS spectra through MASCOT search engine using Swiss-Prot database. We have found the protein Alpha-1-microglobulin/bikunin (AMBP) enriches the PPC from NSCLC patients thus being a potential biomarker, in fact this protein has already been proven to be a potential biomarker of prostate and pancreas cancer. We have identified AMBP both in protein corona and serum. These results suggest that the use of nano particles could be a test able to provide early cancer detection.

Analytical Methods to Characterize and Purify Polymeric Nanoparticles

Advances in polymeric nanoparticles as novel nanomedicines have opened a new class of diagnostic and therapeutic tools for many diseases. However, although the benchtop research studies in the nanoworld are numerous, their translation to currently marketed products is still limited. This lack of transference can be attributed, among other factors, to problems with nanomedicine characterization. Characterization techniques at the nanoscale could be divided in three categories: characterization of physicochemical properties (e.g., size and surface charge), characterization of nanomaterials interactions with biological components (e.g., proteins from the blood), and analytical characterization and purification methods. Currently available literature of this last group only describes methodologies applied for a specific type of nanomaterial or even methods used for bulk materials, which are not completely applicable to nanomaterials. For this reason, the current review aims to become a scholastic guide for those scientists starting in the nanoworld, giving them a description of analytical characterization techniques aimed to analyze polymers forming nanoparticles and possible forms to purify them before being used in preclinical and clinical applications.

Multifunctional Polymer Nanocomposites Reinforced by Aligned Carbon Nanomaterials.

Carbon nanomaterials such as carbon black (CB), carbon nanotubes (CNTs), and graphene have demonstrated significant potential as fillers to improve the electrical, thermal, and mechanical properties of polymers and their fiber-reinforced polymer composites. The level of improvement has been found to depend significantly on the degree of alignment of carbon nanomaterials. Due to the very small scale and complex interactions of carbon nanomaterials with polymers and structural fibers, alignment in a given direction has been a major challenge. Over the past decade, considerable effort has been devoted to developing effective strategies to align carbon nanomaterials in polymer matrices. However, significant technological challenges remain, and there is still a lack of understanding of the alignment mechanisms and their effects on the properties of polymers and composites. This paper reviews in situ alignment techniques including shear deformation, mechanical stretching, electrospinning, and application of an external magnetic or electric field, and ex situ techniques including using vertically grown CNTs or graphene. This review particularly focuses on physical mechanisms underpinning the magnetic or electric field-induced alignment and theoretical analyses that describe the different motions occurring and the major parameters controlling alignment. Moreover, this review highlights the recent research findings of the effects of alignment on the properties of polymer nanocomposites. The outlook towards the challenges and opportunities in this field are also discussed in this review.

Nano Technology in Medicine and Future Implications: A Mini Review

Nanopartides hold great potential in the field of medicine. In this review we have discussed some of the diseases that are treated by the use of nantechnology. Nanotechnology has gained interest in recent years almost in every field with special emphasis on nanomedicine and nanobiology. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. However, it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents under consideration.

Genotoxicity Assessment of Nanomaterials: Recommendations on Best Practices, Assays, and Methods.

Nanomaterials (NMs) present unique challenges in safety evaluation. An international working group, the Genetic Toxicology Technical Committee of the International Life Sciences Institute's Health and Environmental Sciences Institute, has addressed issues related to the genotoxicity assessment of NMs. A critical review of published data has been followed by recommendations on methods alterations and best practices for the standard genotoxicity assays: bacterial reverse mutation (Ames); in vitro mammalian assays for mutations, chromosomal aberrations, micronucleus induction, or DNA strand breaks (comet); and in vivo assays for genetic damage (micronucleus, comet and transgenic mutation assays). The analysis found a great diversity of tests and systems used for in vitro assays; many did not meet criteria for a valid test, and/or did not use validated cells and methods in the Organization for Economic Co-operation and Development Test Guidelines, and so these results could not be interpreted. In vivo assays were less common but better performed. It was not possible to develop conclusions on test system agreement, NM activity, or mechanism of action. However, the limited responses observed for most NMs were consistent with indirect genotoxic effects, rather than direct interaction of NMs with DNA. We propose a revised genotoxicity test battery for NMs that includes in vitro mammalian cell mutagenicity and clastogenicity assessments; in vivo assessments would be added only if warranted by information on specific organ exposure or sequestration of NMs. The bacterial assays are generally uninformative for NMs due to limited particle uptake and possible lack of mechanistic relevance, and are thus omitted in our recommended test battery for NM assessment. Recommendations include NM characterization in the test medium, verification of uptake into target cells, and limited assay-specific methods alterations to avoid interference with uptake or endpoint analysis. These recommendations are summarized in a Roadmap guideline for testing.

Surface-Enhanced Raman Spectroscopy for Bioanalysis: Reliability and Challenges.

Surface-enhanced Raman spectroscopy (SERS) inherits the rich chemical fingerprint information on Raman spectroscopy and gains sensitivity by plasmon-enhanced excitation and scattering. In particular, most Raman peaks have a narrow width suitable for multiplex analysis, and the measurements can be conveniently made under ambient and aqueous conditions. These merits make SERS a very promising technique for studying complex biological systems, and SERS has attracted increasing interest in biorelated analysis. However, there are still great challenges that need to be addressed until it can be widely accepted by the biorelated communities, answer interesting biological questions, and solve fatal clinical problems. SERS applications in bioanalysis involve the complex interactions of plasmonic nanomaterials with biological systems and their environments. The reliability becomes the key issue of bioanalytical SERS in order to extract meaningful information from SERS data. This review provides a comprehensive overview of bioanalytical SERS with the main focus on the reliability issue. We first introduce the mechanism of SERS to guide the design of reliable SERS experiments with high detection sensitivity. We then introduce the current understanding of the interaction of nanomaterials with biological systems, mainly living cells, to guide the design of functionalized SERS nanoparticles for target detection. We further introduce the current status of label-free (direct) and labeled (indirect) SERS detections, for systems from biomolecules, to pathogens, to living cells, and we discuss the potential interferences from experimental design, measurement conditions, and data analysis. In the end, we give an outlook of the key challenges in bioanalytical SERS, including reproducibility, sensitivity, and spatial and time resolution.

Direct Visualization of Thermal Conductivity Suppression Due to Enhanced Phonon Scattering Near Individual Grain Boundaries.

Understanding the impact of lattice imperfections on nanoscale thermal transport is crucial for diverse applications ranging from thermal management to energy conversion. Grain boundaries (GBs) are ubiquitous defects in polycrystalline materials, which scatter phonons and reduce thermal conductivity (κ). Historically, their impact on heat conduction has been studied indirectly through spatially averaged measurements, that provide little information about phonon transport near a single GB. Here, using spatially resolved time-domain thermoreflectance (TDTR) measurements in combination with electron backscatter diffraction (EBSD), we make localized measurements of κ within few μm of individual GBs in boron-doped polycrystalline diamond. We observe strongly suppressed thermal transport near GBs, a reduction in κ from ∼1000 W m-1 K-1 at the center of large grains to ∼400 W m-1 K-1 in the immediate vicinity of GBs. Furthermore, we show that this reduction in κ is measured up to ∼10 μm away from a GB. A theoretical model is proposed that captures the local reduction in phonon mean-free-paths due to strongly diffuse phonon scattering at the disordered grain boundaries. Our results provide a new framework for understanding phonon-defect interactions in nanomaterials, with implications for the use of high-κ polycrystalline materials as heat sinks in electronics thermal management.

In-situ liquid-cell TEM study of radial flow-guided motion of octahedral Au nanoparticles and nanoparticle clusters

The dynamic behavior of octahedral gold nanoparticles (NPs) and nanoparticle clusters (NPCs) in aqueous solution is studied by in-situ liquid-cell transmission electron microscopy (TEM). The octahedral Au NPs/NPCs show preferential orientations in the liquid cell, due to the interaction with the SiNx window. The Au NPs show long-range reversible hopping and three-dimensional (3D) rotational motions in the liquid environment. At the same time, the Au NPCs and NPs perform slow stick-slip and stick-roll motions, respectively, with a centripetal trend. The centripetal motions were explained by a liquid evaporation-induced radial flow model, in which the NPCs/NPs trajectories are controlled by Stokes forces and surface friction by the silicon nitride window. The calculated radius-dependent force (Fc) on the NPCs/NPs shows a semi-linear correlation with the distance r between the NPCs/NPs and the center of mass, accompanied with stochastic fluctuations, in agreement with the model predictions. This work thus demonstrates the effectiveness of in situ liquid-cell TEM for the in-depth understanding of complicated liquid flow and force interactions in nanomaterials.

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context.

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media.

Interactions of Fullerene-Polyglycerol Sulfates at Viral and Cellular Interfaces.

Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water-soluble fullerene-polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV-G) with baby hamster kidney cells serving as a model of host cell. Interference with L-selectin-ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)-based inhibition assay and the leukocyte cell (NALM-6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico- to nanomolar half maximal inhibitory concentrations (IC50 ) are achieved. With their highly antiviral and anti-inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.

Multi-model imaging of the interaction of nanomaterials with cells.

A multi-model X-ray imaging approach was implemented to probe the interaction of nanomaterials with a mammalian cell in three dimensions. With further developments, this approach could have an impact on nanomedicine and nanotoxicology.

A Review of the Cell to Graphene-Based Nanomaterial Interface

The area of cellular interactions of nanomaterials is an important research interest. The sensitivity of cells toward their extracellular matrix allows researchers to create microenvironments for guided stem cell differentiation. Among nanomaterials, graphene, often called the “wonder material,” and its derivatives are at the forefront of such endeavors. Graphene’s carbon backbone, paired with its biocompatibility and ease of functionalization, has been used as an enhanced method of controlled cell proliferation. Graphene’s honeycomb nature allows for compatibility with polymers and biological material for the creation of nanocomposite scaffolds that help differentiation into cell types that have otherwise been proven difficult. Such materials and their role in guiding cell growth can aid the construction of tissue grafts where shortages and patient compatibility create a low success rate. This review will bring together novel studies and techniques used to understand and optimizes graphene’s role in cell growth mechanisms.

Raman studies of the interactions of fibrous carbon nanomaterials with albumin

Adsorption or immobilization of proteins on synthetic surfaces is a key issue in the context of the biocompatibility of implant materials, especially those intended for the needs of cardiac surgery but also for the construction of biosensors or nanomaterials used as drug carriers. The subject of research was the analysis of Raman spectra of two types of fibrous carbon nanomaterials, of great potential for biomedical applications, incubated with human serum albumin (HSA). The first nanomaterial has been created on the layer of MWCNTs deposited by electrophoretic method (EPD) and then covered by thin film of pyrolytic carbon introduced by chemical vapor deposition process (CVD). The second material was formed from carbonized nanofibers prepared via electrospinning (ESCNFs) of polyacrylonitrile (PAN) precursor and then covered with pyrolytic carbon (CVD). The G-band blue-shift towards the position of about 1600cm−1, observed for both studied surfaces, clearly indicates the albumin (HSA) adhesion to the surface. The G and G' (2D) peak shift was employed to assess the stress build up on the carbon nanomaterials. The surface nano- and micro-topography as well as the method of ordering the carbon nanomaterial has a significant influence on the mode of surface-protein interaction.

Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy.

Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials ( i. e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS2 NSs were found to be internalized through three pathways: clathrin → early endosomes → lysosomes, caveolae → early endosomes → lysosomes, and macropinocytosis → late endosomes → lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS2 NSs. Based on these findings, we developed a strategy to achieve effective and synergistic in vivo cancer therapy with MoS2 NSs loaded with low doses of drug through inhibiting exocytosis pathway-induced loss. To the best of our knowledge, this is the first systematic experimental report on the nano-bio interaction of 2D nanomaterials in cells and their application for anti-exocytosis-enhanced synergistic cancer therapy.

The Transferability from Animal Models to Humans: Challenges Regarding Aggregation and Protein Corona Formation of Nanoparticles.

Nanomaterials are interesting candidates for applications in medicine as drug delivery or diagnostic agents. For safe application, they have to be evaluated in in vitro and in vivo models to finally be translated to human clinical trials. However, often those transfer processes fail, and it is not completely understood whether in vitro models leading to these animal models can reliably be compared to the situation in humans. In particular, the interaction of nanomaterials with components from different blood plasma sources is difficult to compare, and the outcomes of those interactions with respect to body distribution and cell uptake are unclear. Therefore, we investigated the interactions of differently functionalized polymeric and inorganic nanoparticles with human, mouse, rabbit, and sheep plasma. The focus was put on the determination of aggregation events of the nanoparticles occurring in concentrated plasma and the correlation with the respectively formed protein coronas. Both the stability in plasma as well as the types of adsorbed proteins were found to strongly depend on the plasma source. Thus, we suggest evaluating the potential use of nanocarriers always in the plasma source of the chosen animal model for in vitro studies as well as in human plasma to pin down differences and eventually enable transfer into clinical trials in humans.

Nano Technology in Medicine and Future Implications: A Mini Review

Nanoparticles hold great potential in the field of medicine. In this review we have discuuded some of the diseases that are treated by the use of nanotechnology. Nanotechnology has gained interest in recent years almost in every field with special emphasis on nanomedicine and nanobiology. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. However, it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents under consideration.

Computational approaches to cell-nanomaterial interactions: keeping balance between therapeutic efficiency and cytotoxicity.

Owing to their unique properties, nanomaterials have been widely used in biomedicine since they have obvious inherent advantages over traditional ones. However, nanomaterials may also cause dysfunction in proteins, genes and cells, resulting in cytotoxic and genotoxic responses. Recently, more and more attention has been paid to these potential toxicities of nanomaterials, especially to the risks of nanomaterials to human health and safety. Therefore, when using nanomaterials for biomedical applications, it is of great importance to keep the balance between therapeutic efficiency and cytotoxicity (i.e., increase the therapeutic efficiency as well as decrease the potential toxicity). This requires a deeper understanding of the interactions between various types of nanomaterials and biological systems at the nano/bio interface. In this review, from the point of view of theoretical researchers, we will present the current status regarding the physical mechanism of cytotoxicity caused by nanomaterials, mainly based on recent simulation results. In addition, the strategies for minimizing the nanotoxicity naturally and artificially will also be discussed in detail. Furthermore, we should notice that toxicity is not always bad for clinical use since causing the death of specific cells is the main way of treating disease. Enhancing the targeting ability of nanomaterials to diseased cells and minimizing their side effects on normal cells will always be hugely challenging issues in nanomedicine. By combining the latest computational studies with some experimental verifications, we will provide special insights into recent advances regarding these problems, especially for the design of novel environment-responsive nanomaterials.

Correction: Computational approaches to cell-nanomaterial interactions: keeping balance between therapeutic efficiency and cytotoxicity.

Correction for 'Computational approaches to cell-nanomaterial interactions: keeping balance between therapeutic efficiency and cytotoxicity' by Hong-ming Ding et al., Nanoscale Horiz., 2018, 3, 6-27.

Molecular Dynamics Simulation of Natural Organic Matter–TiO2 Nanoparticle Interaction in Aqueous Environment: Effects of Ca2+ and Na+ Ions

This work aimed to explore the dynamic properties and mechanisms between natural organic matter and engineered nanomaterials (NOM–ENMs) interactions in aqueous solutions with the existence of monovalent and divalent cations. Due to the limitation of experimental method characterizing the interactions at the atomic level, the molecular dynamics simulation method was used in the study. Comparative interaction processes between NOM and TiO2 nanoparticles in the aqueous solutions with or without Ca2+ and Na+ ions were simulated. Results showed that the Temple-Northeastern-Birmingham (TNB) encircled the TiO2 nanoparticles and formed a horseshoe-style binding by two hydrogen bonds in the absence of cations. However, in the presence of cations, strong attraction between the mediating divalent cations and the negatively charged COO− groups induced the OCOO− atoms to move away from the surface, which resulted in a hinge-style binding. The less TNB fragment encircling the nTiO2 might decrease the steric and electrostatic repulsion between TiO2 nanoparticles coated by humic acid. That is, the Ca2+ might destabilize the TiO2 nanoparticles in the presence of NOM. The mediating effect of Na+ cation on NOM–ENMs interaction is insignificant, whereas the adsorbed Na+ on the surface of the nTiO2 might change the surface charge and potentially affect the environmental behavior of the nTiO2. This study facilitates to understand the fate and potential toxicity of ENMs in the aquatic environments.