Journal: ACS nano
We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined. Analysis of the artificially intelligent nanoarray also showed that each disease has its own unique breathprint, and that the presence of one disease would not screen out others. Cluster analysis showed a reasonable classification power of diseases from the same categories. The effect of confounding clinical and environmental factors on the performance of the nanoarray did not significantly alter the obtained results. The diagnosis and classification power of the nanoarray was also validated by an independent analytical technique, i.e., gas chromatography linked with mass spectrometry. This analysis found that 13 exhaled chemical species, called volatile organic compounds, are associated with certain diseases, and the composition of this assembly of volatile organic compounds differs from one disease to another. Overall, these findings could contribute to one of the most important criteria for successful health intervention in the modern era, viz. easy-to-use, inexpensive (affordable), and miniaturized tools that could also be used for personalized screening, diagnosis, and follow-up of a number of diseases, which can clearly be extended by further development.
Globally ordered colloidal crystal lattices have broad utility in a wide range of optical and catalytic devices, for example, as photonic bandgap materials. However, the self-assembly of stereospecific structures is often confounded by polymorphism. Small free energy differences often characterize ensembles of different structures, making it difficult to produce a single morphology at will. Current techniques to handle this problem adopt one of two approaches: that of the “top-down,” or “bottom-up” methodology, whereby structures are engineered starting from the largest or smallest relevant length scales, respectively. However, recently a third approach for directing high fidelity assembly of colloidal crystals has been suggested which relies on the introduction of polymer co-solutes into the crystal phase [N. A. Mahynski, A. Z. Panagiotopoulos, D. Meng, S. K. Kumar, Nat. Commun., 2014, 5, 4472]. By tuning the polymer’s morphology to interact uniquely with the void symmetry of a single desired crystal, the entropy loss associated with polymer confinement has been shown to strongly bias the formation of that phase. However, previously this approach has only been demonstrated in the limiting case of close-packed crystals. Here we show how this approach may be generalized and extended to complex open crystals, illustrating the utility of this “structure-directing agent” paradigm in engineering the nanoscale structure of ordered colloidal materials. The high degree of transferability of this paradigm’s basic principles between relatively simple crystals and more complex ones suggests this represents a valuable addition to presently known self-assembly techniques.
The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could trigger acute cardiovascular events are emerging, but a fundamental unanswered question remains: Do inhaled nanoparticles translocate from the lung in man and directly contribute to the pathogenesis of cardiovascular disease? In complementary clinical and experimental studies, we used gold nanoparticles to evaluate particle translocation, permitting detection by high-resolution inductively coupled mass spectrometry and Raman microscopy. Healthy volunteers were exposed to nanoparticles by acute inhalation, followed by repeated sampling of blood and urine. Gold was detected in the blood and urine within 15 min to 24 h after exposure, and was still present 3 months after exposure. Levels were greater following inhalation of 5 nm (primary diameter) particles compared to 30 nm particles. Studies in mice demonstrated the accumulation in the blood and liver following pulmonary exposure to a broader size range of gold nanoparticles (2-200 nm primary diameter), with translocation markedly greater for particles <10 nm diameter. Gold nanoparticles preferentially accumulated in inflammation-rich vascular lesions of fat-fed apolipoproteinE-deficient mice. Furthermore, following inhalation, gold particles could be detected in surgical specimens of carotid artery disease from patients at risk of stroke. Translocation of inhaled nanoparticles into the systemic circulation and accumulation at sites of vascular inflammation provides a direct mechanism that can explain the link between environmental nanoparticles and cardiovascular disease and has major implications for risk management in the use of engineered nanomaterials.
Hair loss, a common and distressing symptom, has been plaguing humans. Various pharmacological and nonpharmacological treatments have been widely studied to achieve the desired effect for hair regeneration. As a nonpharmacological physical approach, physiologically appropriate alternating electric field plays a key role in the field of regenerative tissue engineering. Here, a universal motion-activated and wearable electric stimulation device that can effectively promote hair regeneration via random body motions was designed. Significantly facilitated hair regeneration results were obtained from Sprague-Dawley rats and nude mice. Higher hair follicle density and longer hair shaft length were observed on Sprague-Dawley rats when the device was employed compared to conventional pharmacological treatments. The device can also improve the secretion of vascular endothelial growth factor and keratinocyte growth factor and thereby alleviate hair keratin disorder, increase the number of hair follicles, and promote hair regeneration on genetically defective nude mice. This work provides an effective hair regeneration strategy in the context of a nonpharmacological self-powered wearable electronic device.
Root canal therapy (RCT) represents a standard of treatment that addresses infected pulp tissue in teeth and protects against future infection. RCT involves removing dental pulp comprised of blood vessels and nerve tissue, decontaminating residually-infected tissue through biomechanical instrumentation, and root canal obturation using a filler material to replace the space that was previously comprised of dental pulp. Gutta percha (GP) is typically used as the filler material as it is malleable, inert, and biocompatible. While filling the root canal space with GP is the standard of care for endodontic therapies, it has exhibited limitations including leakage, root canal reinfection, and poor mechanical properties. To address these challenges, clinicians have explored the use of alternative root filling materials other than GP. Among the classes of materials that are being explored as novel endodontic therapy platforms, nanodiamonds (NDs) may offer unique advantages due to their favorable properties, particularly for dental applications. These include versatile faceted surface chemistry, biocompatibility, and their role in improving mechanical properties, among others. This study developed a ND-embedded GP (NDGP) that was functionalized with amoxicillin, a broad-spectrum antibiotic commonly used for endodontic infection. Comprehensive materials characterization confirmed improved mechanical properties of NDGP over unmodified GP. In addition, digital radiography and micro-computed tomography imaging demonstrated that obturation of root canals with NDGP could be achieved using clinically-relevant techniques. Furthermore, bacterial growth inhibition assays confirmed drug functionality of NDGP functionalized with amoxicillin. This study demonstrates a promising path towards NDGP implementation in future endodontic therapy for improved treatment outcomes.
To realize the sustainable energy supply in smart city, it is essential to maximize energy scavenging from the city environments for achieving the self-powered functions of some intelligent devices and sensors. Although the solar energy can be well harvested by using existing technologies, the large amounts of wasted wind energy in the city cannot be effectively utilized since the conventional wind turbine generators can only be installed in remote areas due to the large volumes and the safety issues. Here, we rationally design a hybridized nanogenerator, including a solar cell (SC) and a triboelectric nanogenerator (TENG), that can individually/simultaneously scavenging solar and wind energies, which can be extensively installed on the roofs of the city buildings. Under the same device area of about 120 mm×22 mm, the SC can deliver a largest output power of about 8 mW, while the output power of the TENG can be up to 26 mW. Impedance matching between the SC and TENG has been achieved by using a transformer to decrease the impedance of the TENG. The hybridized nanogenerator has a larger output current and a better charging performance than that of the individual SC or TENG. This research presents a feasible approach to maximize solar and wind energies scavenging from the city environments with the aim to realize some self-powered functions in smart city.
The sensing and differentiation of explosive molecules is key for both security and environmental monitoring. Single fluorophores are a widely used tool for explosives detection, but a fluorescent array is a more powerful tool for detecting and differentiating such molecules. By combining array elements into a single multichannel platform; faster results can be obtained from smaller amounts of sample. Here, five explosives are detected and differentiated using quantum dots as luminescent probes in a multichannel platform - 2,4-dinitrotoluene (DNT), 2,4,6-trinitrotoluene (TNT), tetryl (2,4,6-trinitrophenylmethylnitramine), cyclotrimethylenetrinitramine (RDX) and pentaerythritol tetranitrate (PETN). The sharp, variable emissions of the quantum dots, from a single excitation wavelength, make them ideal for such a system. Each colour quantum dot is functionalised with a different surface receptor via a facile ligation process. These receptors undergo non-specific interactions with the explosives, inducing variable fluorescence quenching of the quantum dots. Pattern analysis of the fluorescence quenching data allows for explosive detection and identification with limits-of-detection in the ppb range.
Biodegradable polymeric nanoparticles have the potential to be safer alternatives to viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize polymeric gene delivery nanoparticles and evaluate their efficacy for DNA delivery of herpes simplex virus type I thymidine kinase (HSVtk) combined with the prodrug ganciclovir (GCV) in a malignant glioma model. We investigated polymer structure for gene delivery in two rat glioma cell lines, 9L and F98, to discover nanoparticle formulations more effective than the leading commercial reagent Lipofectamine 2000. The lead polymer structure, poly(1,4-butanediol diacrylate-co-4-amino-1-butanol) end-modified with 1-(3-aminopropyl)-4-methylpiperazine, is a poly(beta-amino ester) (PBAE) and formed nanoparticles with HSVtk DNA that were 138 ± 4 nm in size and 13 ± 1 mV in zeta potential. These nanoparticles containing HSVtk DNA showed 100% cancer cell killing in vitro in the two glioma cell lines when combined with GCV exposure, while control nanoparticles encoding GFP maintained robust cell viability. For in vivo evaluation, tumor-bearing rats were treated with PBAE/HSVtk infusion via convection-enhanced delivery (CED) in combination with systemic administration of GCV. These treated animals showed a significant benefit in survival (p=0.0012 vs. control). Moreover, following a single CED infusion, labeled PBAE nanoparticles spread completely throughout the tumor. This study highlights a nanomedicine approach that is highly promising for the treatment of malignant glioma.
Healthcare acquired infections are a major human health problem, and are becoming increasingly troublesome with the emergence of drug resistant bacteria. Engineered surfaces that reduce the adhesion, proliferation, and spread of bacteria have promise as a mean of preventing infections and reducing the use of antibiotics. To address this need, we created a flexible plastic wrap that combines a hierarchical wrinkled structure with chemical functionalization to reduce bacterial adhesion, biofilm formation, and the transfer of bacteria through an intermediate surface. These hierarchical wraps were effective for reducing biofilm formation of World Health Organization-designated priority pathogens Gram positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram negative Pseudomonas aeruginosa by 87 and 84%, respectively. In addition, these surfaces remain free of bacteria after being touched by a contaminated surface with Gram negative E. coli. We showed that these properties are the result of broad liquid repellency of the engineered surfaces and the presence of reduced anchor points for bacterial adhesion on the hierarchical structure. Such wraps are fabricated using scalable bottom-up techniques and form an effective cover on a variety of complex objects, making them superior to top-down and substrate-specific surface modification methods.
Multidrug-resistance in pathogenic bacteria is an increasing problem in patient care and public health. Molecular nanomachines (MNM) have the ability to open cell membranes using nanomechanical action. We hypothesized that MNM could be used as antibacterial agents by drilling into bacterial cell walls and increasing susceptibility of drug resistant bacteria to recently ineffective antibiotics. We exposed extensively drug resistant K. pneumoniae to light-activated MNM and found that MNM increase susceptibility to meropenem. MNM with meropenem can effectively kill K. pneumoniae that are considered meropenem resistant. We examined the mechanisms of MNM action using permeability assays and transmission electron microscopy, finding that MNM disrupt the cell wall of extensively drug resistant K. pneumoniae, exposing the bacteria to meropenem. These observations suggest that MNM could be used to make conventional antibiotics more efficacious against multidrug-resistant pathogens.