Design and application of inorganic nanoparticle superstructures: current status and future challenges

Self-assembly of inorganic nanoparticles (NPs) into superstructures, which is used as a general way to integrate functional inorganic NPs into macroscale devices, has attracted much research interest. This review will summarize the recent progress and discuss future challenges of the inorganic NP superstructures. Examples include both DNA-based and polymer-based NP assemblies with controlled positioning and geometries, and quasicrystalline ordered structures from the self-assembly of binary or ternary NPs. Different from their individual NP counterparts, these self-assembled superstructures possess unique properties, such as optical chirality and dynamic structural change under an external stimulus. Due to their diversified structures and functionalities, inorganic NP superstructures have shown a wide range of promise for applications in electronic and photonic devices, such as field-effect transistors, magnetoresistive components, optical information recording, and solar cells.     

Cytogenetic and genotoxic effects of zinc oxide nanoparticles on root cells of Allium cepa

Increasing use of zinc oxide nanoparticles (ZnO NP) in consumer products may enhance its release into the environment. Phytotoxicity study is important to understand its possible environmental impact. Allium cepa (Onion bulb) is the best model organism to study genetic toxicology of nanoparticles. Here we have reported cytogenetic and genotoxic effects of ZnO NPs on the root cells of A. cepa. The effects of ZnO NPs on the mitotic index (MI), micronuclei index (MN index), chromosomal aberration index, and lipid peroxidation were determined through the hydroponic culturing of A. cepa. A. cepa roots were treated with the dispersions of ZnO NPs at four different concentrations (25, 50, 75, and 100 μg ml(-1)). With the increasing concentrations of ZnO NPs MI decreased with the increase of pycnotic cells, on the other hand MN and chromosomal aberration index increased. The frequency of micronucleated cells was higher in ZnO NPs treated cells as compared to control (deionized distilled water). The number of cells in each mitotic phase changed upon ZnO NPs treatment. The effect of ZnO NPs on lipid peroxidation as examined by measuring TBARS concentration was evident at all the concentrations compared to bulk ZnO. The TEM image showed internalization of ZnO NPs like particles. SEM image of treated A. cepa demonstrated that the internalized nanoparticles agglomerated depending on the physico-chemical environment inside the cell. Our results demonstrated that ZnO NPs can be a clastogenic/genotoxic and cytotoxic agent. In conclusion, the A. cepa cytogenetic test can be used for the genotoxicity monitoring of novel nanomaterials like ZnO NPs, which is used in many consumer products.     

Hydrodynamic chromatography online with single particle-inductively coupled plasma mass spectrometry for ultratrace detection of metal-containing nanoparticles

Nanoparticle (NP) determination has recently gained considerable interest since a growing number of engineered NPs are being used in commercial products. As a result, their potential to enter the environment and biological systems is increasing. In this study, we report on the development of a hyphenated analytical technique for the detection and characterization of metal-containing NPs, i.e., their metal mass fraction, size, and number concentration. Hydrodynamic chromatography (HDC), suitable for sizing NPs within the range of 5 to 300 nm, was coupled online to inductively coupled plasma mass spectrometry (ICPMS), providing for an extremely selective and sensitive analytical tool for the detection of NPs. However, a serious drawback when operating the ICPMS in its conventional mode is that it does not provide data regarding NP number concentrations and, thus, any information about the metal mass fraction of individual NPs. To address this limitation, we developed single particle (SP) ICPMS coupled online to HDC as an analytical approach suitable for simultaneously determining NP size, NP number concentration, and NP metal content. Gold (Au) NPs of various sizes were used as the model system. To achieve such characterization metrics, three calibrations were required and used to convert ICPMS signal spikes into NPs injected, NP retention time on the HDC column to NP size, and ions detected per signal spike or per NP to metal content in each NP. Two calibration experiments were required in order to make all three calibrations. Also, contour plots were constructed in order to provide for a convenient and most informative viewing of this data. An example of this novel analytical approach was demonstrated for the analysis of Au NPs that had been spiked into drinking water at the ng Au L(-1) level. The described technique gave limits of detection for 60 nm Au NPs of approximately 2.2 ng Au L(-1) or expressed in terms of NP number concentrations of 600 Au NPs mL(-1). These were obtained while the 60 nm NPs exhibited a retention time of 771 s at a mobile phase flow rate of 1 mL min(-1).     

Review: nanoparticles and nanostructured materials in papermaking

The introduction of nanoparticles (NPs) and nanostructured materials (NSMs) in papermaking originally emerged from the perspective of improving processing operations and reducing material consumption. However, a very broad range of nanomaterials (NMs) can be incorporated into the paper structure and allows creating paper products with novel properties. This review is of interdisciplinary nature, addressing the emerging area of nanotechnology in papermaking focusing on resources, chemical synthesis and processing, colloidal properties, and deposition methods. An overview of different NMs used in papermaking together with their intrinsic properties and a link to possible applications is presented from a chemical point of view. After a brief introduction on NMs classification and papermaking, their role as additives or pigments in the paper structure is described. The different compositions and morphologies of NMs and NSMs are included, based on wood components, inorganic, organic, carbon-based, and composite NPs. In a first approach, nanopaper substrates are made from fibrillary NPs, including cellulose-based or carbon-based NMs. In a second approach, the NPs can be added to a regular wood pulp as nanofillers or used in coating compositions as nanopigments. The most important processing steps for NMs in papermaking are illustrated including the internal filling of fiber lumen, LbL deposition or fiber wall modification, with important advances in the field on the in situ deposition of NPs on the paper fibers. Usually, the manufacture of products with advanced functionality is associated with complex processes and hazardous materials. A key to success is in understanding how the NMs, cellulose matrix, functional additives, and processes all interact to provide the intended paper functionality while reducing materials waste and keeping the processes simple and energy efficient.     

Multifunctional Nanoparticle@MOF Core–Shell Nanostructures

Controllable integration of inorganic nanoparticles (NPs) and metal–organic frameworks (MOFs) is leading to the creation of many new multifunctional materials. In this Research News, an emerging type of core–shell nanostructure, in which the inorganic NP cores are encapsulated by the MOF shells, is briefly introduced. Unique functions originating from the property synergies of different types of inorganic NP cores and MOF shells are highlighted, and insight into their future development is suggested. It is highly expected that this Research News could arouse research enthusiasm on such NP@MOF core–shell nanostructures, which have great application potential in devices, energy, the environment, and medicine.     

Impact of nonconductive powder on electrostatic separation for recycling crushed waste printed circuit board

The electrostatic separation is an effective and environmentally friendly method for recycling metals and nonmetals from crushed printed circuit board (PCB) wastes. However, it still confronts some problems brought by nonconductive powder (NP). Firstly, the NP is fine and liable to aggregate. This leads to an increase of middling products and loss of metals. Secondly, the stability of separation process is influenced by NP. Finally, some NPs accumulate on the surface of the corona and electrostatic electrodes during the process. These problems lead to an inefficient separation. In the present research, the impacts of NP on electrostatic separation are investigated. The experimental results show that: the separation is notably influenced when the NP content is more than 10%. With the increase of NP content, the middling products sharply increase from 1.4 g to 4.3g (increase 207.1%), while the conductive products decrease from 24.0 g to 19.1g (decrease 20.4%), and the separation process become more instable.     

Mass Cytometry and Single‐Cell RNA‐seq Profiling of the Heterogeneity in Human Peripheral Blood Mononuclear Cells Interacting with Silver Nanoparticles

Understanding the interactions between nanoparticles (NPs) and human immune cells is necessary for justifying their utilization in consumer products and biomedical applications. However, conventional assays may be insufficient in describing the complexity and heterogeneity of cell–NP interactions. Herein, mass cytometry and single‐cell RNA‐sequencing (scRNA‐seq) are complementarily used to investigate the heterogeneous interactions between silver nanoparticles (AgNPs) and primary immune cells. Mass cytometry reveals the heterogeneous biodistribution of the positively charged polyethylenimine‐coated AgNPs in various cell types and finds that monocytes and B cells have higher association with the AgNPs than other populations. scRNA‐seq data of these two cell types demonstrate that each type has distinct responses to AgNP treatment: NRF2‐mediated oxidative stress is confined to B cells, whereas monocytes show Fcγ‐mediated phagocytosis. Besides the between‐population heterogeneity, analysis of single‐cell dose–response relationships further reveals within‐population diversity for the B cells and naïve CD4⁺ T cells. Distinct subsets having different levels of cellular responses with respect to their cellular AgNP doses are found. This study demonstrates that the complementary use of mass cytometry and scRNA‐seq is helpful for gaining in‐depth knowledge on the heterogeneous interactions between immune cells and NPs and can be incorporated into future toxicity assessments of nanomaterials.     

Nanoparticle–Plant Interactions: Two‐Way Traffic

In this Review, an effort is made to discuss the most recent progress and future trend in the two‐way traffic of the interactions between plants and nanoparticles (NPs). One way is the use of plants to synthesize NPs in an environmentally benign manner with a focus on the mechanism and optimization of the synthesis. Another way is the effects of synthetic NPs on plant fate with a focus on the transport mechanisms of NPs within plants as well as NP‐mediated seed germination and plant development. When NPs are in soil, they can be adsorbed at the root surface, followed by their uptake and inter/intracellular movement in the plant tissues. NPs may also be taken up by foliage under aerial deposition, largely through stomata, trichomes, and cuticles, but the exact mode of NP entry into plants is not well documented. The NP–plant interactions may lead to inhibitory or stimulatory effects on seed germination and plant development, depending on NP compositions, concentrations, and plant species. In numerous cases, radiation‐absorbing efficiency, CO₂ assimilation capacity, and delay of chloroplast aging have been reported in the plant response to NP treatments, although the mechanisms involved in these processes remain to be studied.     

One‐Dimensional Assemblies of Nanoparticles: Preparation,Properties, and Promise

Nanoparticle (NP) assemblies are of considerable interest for both fundamental research and applications, since they provide direct bridges between nanometer‐scale objects and the macroscale world. Unlike two‐dimensional or three‐dimensional NP assemblies, which have been extensively studied and reviewed, reports on one‐dimensional (1D) NP assemblies are rather rare, even though these assemblies are likely to play critical roles in the improvement of the efficiencies of various electronic, optoelectronic, magnetic, and other devices based on single NPs or their composites. Additionally, 1D assemblies of NPs, i.e., chains, can significantly help in the understanding of a number of biological processes and fundamental quantum mechanics of nanometer‐scale systems. The difficulties are very evident when one wants to realize anisotropic 1D assemblies from presumably isotropic, zero‐dimensional NPs. In this context, the authors present a systemic review of current research on 1D NP assemblies. Their preparation methods are classified and novel characteristics of NP chains, such as collective properties and directional transfer of photons, electrons, spins, etc., are elucidated. Current problems underlying the fundamental research and practical applications of 1D NP assemblies are also addressed.     

Development of an anti-influenza drug screening assay targeting nucleoproteins with tryptophan fluorescence quenching

Recent studies have shown that NP (nucleoprotein), which possesses multiple functions in the viral life cycle, is a new potential anti-influenza drug target. NP inhibitors reliably induce conformational changes in NPs, and these changes may confer inhibition of the influenza virus. The six conserved tryptophan residues in NP can be used as an intrinsic probe to monitor the change in fluorescence of the tryptophan residues in the protein upon binding to an NP inhibitor. In the present study, we found that the fluorescence of recombinant NP proteins was quenched following the binding of available NP inhibitors (such as nucleozin) in a concentration- and time-dependent manner, which suggests that the inhibitor induced conformational changes in the NPs. The minimal fluorescence-quenching effect and weak binding constant of nucleozin to the swine-origin influenza virus H1N1pdm09 (SOIV) NP revealed that the SOIV is resistant to nucleozin. We have used the fluorescence-quenching property of tryptophans in NPs that were bound to ligands in a 96-well-plate-based drug screen to assess the ability of promising small molecules to interact with NPs and have identified one new anti-influenza drug, CSV0C001018, with a high SI value. This convenient method for drug screening may facilitate the development of antiviral drugs that target viruses other than the influenza virus, such as HIV and HBV.     

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

Development of nanoparticle (NP) based therapies to promote regeneration in sites of central nervous system (CNS;i.e.brain and spinal cord) pathology relies critically on the availability of experimental models that offer biologically valid predictions of NP fate in vivo.However,there is a major lack of biological models that mimic the pathological complexity of target neural sites in vivo,particularly the responses of resident neural immune cells to NPs.Here,we have utilised a previously developed in vitro model of traumatic spinal cord injury (based on 3-D organotypic slice arrays) with dynamic time lapse imaging to reveal in real-time the acute cellular fate of NPs within injury foci.We demonstrate the utility of our model in revealing the well documented phenomenon of avid NP sequestration by the intrinsic immune cells of the CNS (the microglia).Such immune sequestration is a known translational barrier to the use of NP-based therapeutics for neurological injury.Accordingly,we suggest that the utility of our model in mimicking microglial sequestration behaviours offers a valuable investigative tool to evaluate strategies to overcome this cellular response within a simple and biologically relevant experimental system,whilst reducing the use of live animal neurological injury models for such studies.     

Water-Induced Separation of Polymers from High Nanoparticle-Content Nanocomposite Films

Polymer nanocomposites with high loadings of nanoparticles (NPs) exhibit exceptional mechanical and transport properties. Separation of polymers and NPs from such nanocomposites is a critical step in enabling the recycling of these components and reducing the potential environmental hazards that can be caused by the accumulation of nanocomposite wastes in landfills. However, the separation typically requires the use of organic solvents or energy-intensive processes. Using polydimethylsiloxane (PDMS)-infiltrated SiO₂ NP films, we demonstrate that the polymers can be separated from the SiO₂ NP packings when these nanocomposites are exposed to high humidity and water. The findings indicate that the charge state of the NPs plays a significant role in the propensity of water to undergo capillary condensation within the PDMS-filled interstitial pores. We also show that the size of NPs has a crucial impact on the kinetics and extent of PDMS expulsion, illustrating the importance of capillary forces in inducing PDMS expulsion. We demonstrate that the separated polymer can be collected and reused to produce a new nanocomposite film. The work provides insightful guidelines on how to design and fabricate end-of-life recyclable high-performance nanocomposites.     

Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting—two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing. In tumor invasive margin patient cells, the stimuli-responsive multifunctional NPs target GBM cells, enhance cell uptake by 12-fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long-term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli-responsive multifunctional NPs as an effective anti-GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.     

Tuning Cellular Response to Nanoparticles via Surface Chemistry and Aggregation

The aggregation of gold nanoparticles (Au NPs) in cell media is a common phenomenon that can influence NP‐cell interactions. Here, we control Au NP aggregation in cell media and study the impact of Au NP aggregation on human dermal fibroblast (HDF) cells. By first adding Au NPs to fetal bovine serum (FBS) and then subsequently to a buffer, aggregation can be avoided. Aggregation of Au NPs also can be avoided by coating Au NPs with other biomolecules such as lipids. The aggregation state of the Au NPs influences cellular toxicity and Au NP uptake: non‐aggregated cationic Au NPs are four‐fold less toxic to HDF cells than aggregated cationic Au NPs, and the uptake of non‐aggregated anionic citrate Au NPs is three orders of magnitude less than that of aggregated citrate Au NPs. Upon uptake of Au NPs, cellular F‐actin fiber formation is disrupted and actin dots are predominant. When lipid‐coated Au NPs are doped with a fluorescent lipid (F‐lipid) and incubated with HDF cells, the fluorescence from the F‐lipid was found throughout the cell, showing that lipids can dissociate from the Au NP surface upon entering the cell.     

Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles

A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs.The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern.However,it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability.Glioblastoma multiforme,the most malignant orthotopic brain tumor,presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment.Herein,we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance.Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3x relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0x)than did the larger AuNPs.Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation.The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4x) than that of the 18-nm AuNPs.Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium.Taken together,our results suggest that the 3-nm AuNPs,characterized by enhanced permeability and retention,are able to target brain tumors and undergo renal clearance.     

Uptake and Intracellular Fate of Engineered Nanoparticles in Mammalian Cells: Capabilities and Limitations of Transmission Electron Microscopy—Polymer‐Based Nanoparticles

In order to elucidate mechanisms of nanoparticle (NP)–cell interactions, a detailed knowledge about membrane–particle interactions, intracellular distributions, and nucleus penetration capabilities, etc. becomes indispensable. The utilization of NPs as additives in many consumer products, as well as the increasing interest of tailor‐made nanoobjects as novel therapeutic and diagnostic platforms, makes it essential to gain deeper insights about their biological effects. Transmission electron microscopy (TEM) represents an outstanding method to study the uptake and intracellular fate of NPs, since this technique provides a resolution far better than the particle size. Additionally, its capability to highlight ultrastructural details of the cellular interior as well as membrane features is unmatched by other approaches. Here, a summary is provided on studies utilizing TEM to investigate the uptake and mode‐of‐action of tailor‐made polymer nanoparticles in mammalian cells. For this purpose, the capabilities as well as limitations of TEM investigations are discussed to provide a detailed overview on uptake studies of common nanoparticle systems supported by TEM investigations. Furthermore, methodologies that can, in particular, address low‐contrast materials in electron microscopy, i.e., polymeric and polymer‐modified nanoparticles, are highlighted.     

Water‐Dispersible,Multifunctional, Magnetic,Luminescent Silica‐Encapsulated Composite Nanotubes

A multifunctional one‐dimensional nanostructure incorporating both CdSe quantum dots (QDs) and Fe₃O₄ nanoparticles (NPs) within a SiO₂‐nanotube matrix is successfully synthesized based on the self‐assembly of preformed functional NPs, allowing for control over the size and amount of NPs contained within the composite nanostructures. This specific nanostructure is distinctive because both the favorable photoluminescent and magnetic properties of QD and NP building blocks are incorporated and retained within the final silica‐based composite, thus rendering it susceptible to both magnetic guidance and optical tracking. Moreover, the resulting hydrophilic nanocomposites are found to easily enter into the interiors of HeLa cells without damage, thereby highlighting their capability not only as fluorescent probes but also as possible drug‐delivery vehicles of interest in nanobiotechnology.     

Characterizing the Lateral Friction of Nanoparticles on On‐Chip Integrated Black Lipid Membranes

The use of nanoparticles (NPs) in biomedical applications creates a need for appropriate model systems to systematically investigate NP–membrane interactions under well‐defined conditions. Black lipid membranes (BLMs) are free‐floating membranes with defined composition that are ideally suited for characterizing NP–membrane interactions free of any potential perturbation through a supporting substrate. Herein, arrays of microfabricated BLMs are integrated into a chip‐based platform that is compatible with high‐speed optical NP tracking. This system is used to investigate the lateral diffusion of 40 nm gold spheres tethered to biotinylated lipids through antibody‐functionalized ligands (single‐stranded DNA or polyethylene glycol). Although the NPs show an almost free and ergodic diffusion, their lateral motion is subject to substantial drag at the membrane surface, which leads to systematically smaller diffusion coefficients than those obtained for lipids in the membrane through fluorescence recovery after photobleaching. The lateral mobility of the NPs is influenced by the chemical composition and salt concentration at the NP‐membrane interface, but is independent of the ligand density in the membrane. Together with the observation that nanoprisms, which have a larger relative contact area with the membrane than spherical NPs, show an even slower diffusion, these findings indicate that the lateral mobility of NPs tethered in close vicinity to a membrane is significantly reduced by the friction at the NP‐membrane interface.     

Nucleic acid and nucleotide-mediated synthesis of inorganic nanoparticles

Since the advent of practical methods for achieving DNA metallization, the use of nucleic acids as templates for the synthesis of inorganic nanoparticles (NPs) has become an active area of study. It is now widely recognized that nucleic acids have the ability to control the growth and morphology of inorganic NPs. These biopolymers are particularly appealing as templating agents as their ease of synthesis in conjunction with the possibility of screening nucleotide composition, sequence and length, provides the means to modulate the physico-chemical properties of the resulting NPs. Several synthetic procedures leading to NPs with interesting photophysical properties as well as studies aimed at rationalizing the mechanism of nucleic acid-templated NP synthesis are now being reported. This progress article will outline the current understanding of the nucleic acid-templated process and provides an up to date reference in this nascent field.