Lessons from the history of inorganic nanoparticles for inhalable diagnostics and therapeutics.

The respiratory tract is one of the most accessible ones to exogenous nanoparticles, yet drug delivery by their means to it is made extraordinarily challenging because of the plexus of aerodynamic, hemodynamic and biomolecular factors at cellular and extracellular levels that synergistically define the safety and efficacy of this process. Here, the use of inorganic nanoparticles (INPs) for inhalable diagnostics and therapies of the lung is viewed through the prism of the history of studies on the interaction of INPs with the lower respiratory tract. The most conceptually and methodologically innovative and illuminative studies are referred to in the chronological order, as they were reported in the literature, and the trends in the progress of understanding this interaction of immense therapeutic and toxicological significance are being deduced from it. The most outstanding actual trends delineated include the diminishment of toxicity via surface functionalization, cell targeting, tagging and tracking via controlled binding and uptake, hybrid INP treatments, magnetic guidance, combined drug and gene delivery, use as adjuvants in inhalable vaccines, and other. Many of the understudied research directions, which have been accomplished by the nanostructured organic polymers in the pulmonary niche, are discussed. The progress in the use of INPs as inhalable diagnostics or therapeutics has been hampered by their well-recognized inflammatory potential and toxicity in the respiratory tract. However, the annual numbers of methodologically innovative studies have been on the rise throughout the past two decades, suggesting that this is a prolific direction of research, its comparatively poor commercial takings notwithstanding. Still, the lack of consensus on the effects of many INP compositions at low but therapeutically effective doses, the plethora of contradictory reports on ostensibly identical chemical compositions and NP properties, and the many cases of antagonism in combinatorial NP treatments imply that the rational design of inhalable medical devices based on INPs must rely on qualitative principles for the most part and embrace a partially stochastic approach as well. At the same time, the fact that the most studied INPs for pulmonary applications have been those with some of the thickest records of pulmonary toxicity, e.g., carbon, silver, gold, silica and iron oxide, is a silent call for the expansion of the search for new inorganic compositions for use in inhalable therapies to new territories.

Mechanisms of immune response to inorganic nanoparticles and their degradation products.

Careful assessment of the biological fate and immune response of inorganic nanoparticles is crucial for use of such carriers in drug delivery and other biomedical applications. Many studies have elucidated the cellular and molecular mechanisms of the interaction of inorganic nanoparticles with the components of the immune system. The biodegradation and dissolution of inorganic nanoparticles can influence their ensuing immune response. While the immunological properties of inorganic nanoparticles as a function of their physicochemical properties have been investigated in detail, little attention has been paid to the immune adverse effects towards the degradation products of these nanoparticles. To fill this gap, we herein summarize the cellular mechanisms of immune response to inorganic nanoparticles and their degradation products with specific focus on immune cells. We also accentuate the importance of designing new methods and instruments for the in situ characterization of inorganic nanoparticles in order to assess their safety as a result of degradation. This review further sheds light on factors that need to be considered in the design of safe and effective inorganic nanoparticles for use in delivery of bioactive and imaging agents.

Using semantics to scale up evidence-based chemical risk-assessments.

BACKGROUND: The manual processes used for risk assessments are not scaling to the amount of data available. Although automated approaches appear promising, they must be transparent in a public policy setting. OBJECTIVE: Our goal is to create an automated approach that moves beyond retrieval to the extraction step of the information synthesis process, where evidence is characterized as supporting, refuting, or neutral with respect to a given outcome. METHODS: We combine knowledge resources and natural language processing to resolve coordinated ellipses and thus avoid surface level differences between concepts in an ontology and outcomes in an abstract. As with a systematic review, the search criterion, and inclusion and exclusion criterion are explicit. RESULTS: The system scales to 482K abstracts on 27 chemicals. Results for three endpoints that are critical for cancer risk assessments show that refuting evidence (where the outcome decreased) was higher for cell proliferation (45.9%), and general cell changes (37.7%) than for cell death (25.0%). Moreover, cell death was the only end point where supporting claims were the majority (61.3%). If the number of abstracts that measure an outcome was used as a proxy for association there would be a stronger association with cell proliferation than cell death (20/27 chemicals). However, if the amount of supporting evidence was used (where the outcome increased) the conclusion would change for 21/27 chemicals (20 from proliferation to death and 1 from death to proliferation). CONCLUSIONS: We provide decision makers with a visual representation of supporting, neutral, and refuting evidence whilst maintaining the reproducibility and transparency needed for public policy. Our findings show that results from the retrieval step where the number of abstracts that measure an outcome are reported can be misleading if not accompanied with results from the extraction step where the directionality of the outcome is established.

Antimicrobial Resistance and Inorganic Nanoparticles.

Antibiotics are being less effective, which leads to high mortality in patients with infections and a high cost for the recovery of health, and the projections that are had for the future are not very encouraging which has led to consider antimicrobial resistance as a global health problem and to be the object of study by researchers. Although resistance to antibiotics occurs naturally, its appearance and spread have been increasing rapidly due to the inappropriate use of antibiotics in recent decades. A bacterium becomes resistant due to the transfer of genes encoding antibiotic resistance. Bacteria constantly mutate; therefore, their defense mechanisms mutate, as well. Nanotechnology plays a key role in antimicrobial resistance due to materials modified at the nanometer scale, allowing large numbers of molecules to assemble to have a dynamic interface. These nanomaterials act as carriers, and their design is mainly focused on introducing the temporal and spatial release of the payload of antibiotics. In addition, they generate new antimicrobial modalities for the bacteria, which are not capable of protecting themselves. So, nanoparticles are an adjunct mechanism to improve drug potency by reducing overall antibiotic exposure. These nanostructures can overcome cell barriers and deliver antibiotics to the cytoplasm to inhibit bacteria. This work aims to give a general vision between the antibiotics, the nanoparticles used as carriers, bacteria resistance, and the possible mechanisms that occur between them.

Near infrared photothermal conversion materials: mechanism, preparation, and photothermal cancer therapy applications.

Photothermal therapy (PTT) has been widely applied in cancer therapy as a result of its non-invasive, localized treatment and good therapeutic effect. In general, the final therapeutic effect of PTT mainly depends on the photothermal materials, which can be further considered to be determined by the photothermal conversion efficiency, biocompatibility, and photothermal stability of photothermal materials. In this review, photothermal materials including inorganic materials, organic materials, and organic-inorganic composite materials in recent years have been summarized in terms of the mechanism, preparation, and cancer therapy applications. In the end, the perspectives and obstacles in their further development are overviewed.

Inorganic radiopharmaceutical chemistry of oxine.

8-Hydroxyquinoline (8-HQ, oxine) is a small, monoprotic, bicyclic aromatic compound and its relative donor group orientation imparts impressive bidentate metal chelating abilities that have been exploited in a vast array of applications over decades. 8-HQ and its derivatives have been explored in medicinal applications including anti-neurodegeneration, anticancer properties, and antimicrobial activities. One long established use of 8-HQ in medicinal inorganic chemistry is the coordination of radioactive isotopes of metal ions in nuclear medicine. The metal-oxine complex with the single photon emission computed tomography (SPECT) imaging isotope [111In]In3+ was developed in the 1970s and 1980s to radiolabel leukocytes for inflammation and infection imaging. The [111In][In(oxine)3] complex functions as an ionophore: a moderately stable lipophilic complex to enter cells; however, inside the cell environment [111In]In3+ undergoes exchange and remains localized. As new developments have progressed towards radiopharmaceuticals capable of both imaging and therapy (theranostics), 8-HQ has been re-explored in recent years to investigate its potential to chelate larger radiometal ions with longer half-lives and different indications. Further, metal-oxine complexes have been used to study liposomes and other nanomaterials by tracking these nanomedicines in vivo. Expanding 8-HQ to multidentate ligands for highly thermodynamically stable and kinetically inert complexes has increased the possibilities of this small molecule in nuclear medicine. This article outlines the historic use of metal-oxine complexes in inorganic radiopharmaceutical chemistry, with a focus on recent advances highlighting the possibilities of developing higher denticity, targeted bifunctional chelators with 8-HQ.

Ab Initio Machine Learning in Chemical Compound Space.

Chemical compound space (CCS), the set of all theoretically conceivable combinations of chemical elements and (meta-)stable geometries that make up matter, is colossal. The first-principles based virtual sampling of this space, for example, in search of novel molecules or materials which exhibit desirable properties, is therefore prohibitive for all but the smallest subsets and simplest properties. We review studies aimed at tackling this challenge using modern machine learning techniques based on (i) synthetic data, typically generated using quantum mechanics based methods, and (ii) model architectures inspired by quantum mechanics. Such Quantum mechanics based Machine Learning (QML) approaches combine the numerical efficiency of statistical surrogate models with an ab initio view on matter. They rigorously reflect the underlying physics in order to reach universality and transferability across CCS. While state-of-the-art approximations to quantum problems impose severe computational bottlenecks, recent QML based developments indicate the possibility of substantial acceleration without sacrificing the predictive power of quantum mechanics.

Differential effects of inorganic salts on cellulase kinetics in enzymatic saccharification of cellulose and lignocellulosic biomass.

Inorganic salt pretreatment of lignocellulosic biomass has proven to be an efficient way to increase the efficiency of enzymatic saccharification. However, it is not clear that this improvement is the result of modification of the lignocellulosic substrate after pretreatment, or removal of inhibitor, or enhancement of cellulase or a combination of these events. Therefore, this study aimed to analyze the effects of inorganic salts on kinetics of cellulase enzymes (celluclast 1.5L and accellerase 1500). Two substrates rich in cellulose content [carboxymethylcellulose (CMC), avicel (AV)] and lignocellulose substrate [sugarcane bagasse (SB)] were considered. The enzymatic saccharification was carried with and without the addition of inorganic salts (NaCl and KCl) at 0.5 M and 1.0 M concentration. The kinetic parameters, Km and Vm, were determined to mechanically understand the pattern of inhibition and enhancement of inorganic salts on enzymatic saccharification. The kinetics parameters of celluclast 1.5L and accellerase 1500 for hydrolysis of CMC and AV with NaCl showed uncompetitive inhibition. Whereas, influences of KCl on both cellulase were differentiated to function in inhibition or enhancement modes when challenged with different substrates. On the other hand, enzymatic hydrolysis efficiencies of SB using both cellulases were enhanced under addition of NaCl and KCl, by increasing Vm of celluclast 1.5L from 0.303 to 0.635 mg/mL min (0.5 M KCl) and accellerase 1500 from 0.383 to 0.719 mg/mL min (1.0 M NaCl). The details of kinetic analysis in this work revealed the mechanism of inorganic salts on cellulase kinetics to be involved in substrate modification and removal of inhibitor.

Physico-Chemical Properties of Inorganic NPs Influence the Absorption Rate of Aquatic Mosses Reducing Cytotoxicity on Intestinal Epithelial Barrier Model.

Noble metals nanoparticles (NPs) and metal oxide NPs are widely used in different fields of application and commercial products, exposing living organisms to their potential adverse effects. Recent evidences suggest their presence in the aquifers water and consequently in drinking water. In this work, we have carefully synthesized four types of NPs, namely, silver and gold NPs (Ag NPs and Au NPs) and silica and titanium dioxide NPs (SiO2 NPs and TiO2 NPs) having a similar size and negatively charged surfaces. The synthesis of Ag NPs and Au NPs was carried out by colloidal route using silver nitrate (AgNO3) and tetrachloroauric (III) acid (HAuCl4) while SiO2 NPs and TiO2 NPs were achieved by ternary microemulsion and sol-gel routes, respectively. Once the characterization of NPs was carried out in order to assess their physico-chemical properties, their impact on living cells was studied. We used the human colorectal adenocarcinoma cells (Caco-2), known as the best representative intestinal epithelial barrier model to understand the effects triggered by NPs through ingestion. Then, we moved to explore how water contamination caused by NPs can be lowered by the ability of three species of aquatic moss, namely, Leptodictyum riparium, Vesicularia ferriei, and Taxiphyllum barbieri, to absorb them. The experiments were conducted using two concentrations of NPs (100 µM and 500 Μm as metal content) and two time points (24 h and 48 h), showing a capture rate dependent on the moss species and NPs type. Then, the selected moss species, able to actively capture NPs, appear as a powerful tool capable to purify water from nanostructured materials, and then, to reduce the toxicity associated to the ingestion of contaminated drinking water.

Development of a 3D printable and highly stretchable ternary organic-inorganic nanocomposite hydrogel.

Hydrogels that can be processed with additive manufacturing techniques and concomitantly possess favorable mechanical properties are interesting for many advanced applications. However, the development of novel ink materials with high intrinsic 3D printing performance has been proven to be a major challenge. Herein, a novel 3D printable organic-inorganic hybrid hydrogel is developed from three components, and characterized in detail in terms of rheological property, swelling behavior and composition. The nanocomposite hydrogel combines a thermoresponsive hydrogel with clay LAPONITE® XLG and in situ polymerized poly(N,N-dimethylacrylamide). Before in situ polymerization, the thermogelling and shear thinning properties of the thermoresponsive hydrogel provides a system well-suited for extrusion-based 3D printing. After chemical curing of the 3D-printed constructs by free radical polymerization, the resulting interpenetrating polymer network hydrogel shows excellent mechanical strength with a high stretchability to a tensile strain at break exceeding 550%. Integrating with the advanced 3D-printing technique, the introduced material could be interesting for a wide range of applications including tissue engineering, drug delivery, soft robotics and additive manufacturing in general.

Inorganic Elements in Mytilus galloprovincialis Shells: Geographic Traceability by Multivariate Analysis of ICP-MS Data.

The international seafood trade is based on food safety, quality, sustainability, and traceability. Mussels are bio-accumulative sessile organisms that need regular control to guarantee their safe consumption. However, no well-established and validated methods exist to trace mussel origin, even if several attempts have been made over the years. Recently, an inorganic multi-elemental fingerprint coupled to multivariate statistics has increasingly been applied in food quality control. The mussel shell can be an excellent reservoir of foreign inorganic chemical species, allowing recording long-term environmental changes. The present work investigates the multi-elemental composition of mussel shells, including Al, Cu, Cr, Zn, Mn, Cd, Co, U, Ba, Ni, Pb, Mg, Sr, and Ca, determined by inductively-coupled plasma mass-spectrometry in Mytilus galloprovincialis collected along the Central Adriatic Coast (Marche Region, Italy) at 25 different sampling sites (18 farms and 7 natural banks) located in seven areas. The experimental data, coupled with chemometric approaches (principal components analysis and linear discriminant analysis), were used to create a statistical model able to discriminate samples as a function of their production site. The LDA model is suitable for achieving a correct assignment of >90% of individuals sampled to their respective harvesting locations and for being applied to counteract fraud.

Intermediate state representation approach to physical properties of molecular electron-attached states: Theory, implementation, and benchmarking.

Computational schemes for comprehensive studies of molecular electron-attached states and the calculation of electron affinities (EAs) are formulated and implemented employing the intermediate state representation (ISR) formalism and the algebraic-diagrammatic construction approximation for the electron propagator (EA-ADC). These EA-ADC(n)/ISR(m) schemes allow for a consistent treatment of not only electron affinities and pole strengths up to third-order of perturbation theory (n = 3) but also one-electron properties of electron-attached states up to second order (m = 2). The EA-ADC/ISR equations were implemented in the Q-Chem program for Sz-adapted intermediate states, allowing also open-shell systems to be studied using unrestricted Hartree-Fock references. For benchmarking of the EA-(U)ADC/ISR schemes, EAs and dipole moments of various electron-attached states of small closed- and open-shell molecules were computed and compared to full configuration interaction data. As an illustrative example, EA-ADC(3)/ISR(2) has been applied to the thymine-thymine (6-4) DNA photolesion.

Inorganic Enzyme Mimics.

Enzyme mimics (or artificial enzymes) have emerged as valuable alternatives to natural enzymes since the pioneering work of Ronald Breslow. They have numerous advantages over natural enzymes, such as high stability, low cost, and tailorable activity. Among varieties of materials explored to mimic enzymes, the inorganic ones, including inorganic complexes and nanomaterials, have attracted increasing interest over the last decade and have the potential to address the current challenges in energy, environment, health, etc.

Sol-gel process: the inorganic approach in protein imprinting.

Proteins play a central role in the signal transmission in living systems since they are able to recognize specific biomolecules acting as cellular receptors, antibodies or enzymes, being themselves recognized by other proteins in protein/protein interactions, or displaying epitopes suitable for antibody binding. In this context, the specific recognition of a given protein unlocks a range of interesting applications in diagnosis and in targeted therapies. Obviously, this role is already fulfilled by antibodies with unquestionable success. However, the design of synthetic artificial systems able to endorse this role is still challenging with a special interest to overcome limitations of antibodies, in particular their production and their stability. Molecular Imprinted Polymers (MIPs) are attractive recognition systems which could be an alternative for the specific capture of proteins in complex biological fluids. MIPs can be considered as biomimetic receptors or antibody mimics displaying artificial paratopes. However, MIPs of proteins remains a challenge due to their large size and conformational flexibility, their complex chemical nature with multiple recognition sites and their low solubility in most organic solvents. Classical MIP synthesis conditions result in large polymeric cavities and unspecific binding sites on the surface. In this review, the potential of the sol-gel process as inorganic polymerization strategy to overcome the drawbacks of protein imprinting is highlighted. Thanks to the mild and biocompatible experimental conditions required and the use of water as a solvent, the inorganic polymerization approach better suited to proteins than organic polymerization. Through numerous examples and applications of MIPs, we proposed a critical evaluation of the parameters that must be carefully controlled to achieve sol-gel protein imprinting (SGPI), including the choice of the monomers taking part in the polymerization.

Environment-Induced Reversible Modulation of Optical and Electronic Properties of Lead Halide Perovskites and Possible Applications to Sensor Development: A Review.

Lead halide perovskites are currently widely investigated as active materials in photonic and optoelectronic devices. While the lack of long term stability actually limits their application to commercial devices, several experiments demonstrated that beyond the irreversible variation of the material properties due to degradation, several possibilities exist to reversibly modulate the perovskite characteristics by acting on the environmental conditions. These results clear the way to possible applications of lead halide perovskites to resistive and optical sensors. In this review we will describe the current state of the art of the comprehension of the environmental effects on the optical and electronic properties of lead halide perovskites, and of the exploitation of these results for the development of perovskite-based sensors.

Imaging inorganic nanomaterial fate down to the organelle level.

Nanotoxicology remains an important and emerging field since only recent years have seen the improvement of biological models and exposure setups toward real-life scenarios. The appropriate analysis of nanomaterial fate in these conditions also required methodological developments in imaging to become sensitive enough and element specific. In the last 2-4 years, impressive breakthroughs have been achieved using electron microscopy, nanoscale secondary ion mass spectrometry, X-ray fluorescence microscopy, or fluorescent sensors. In this review, basics of the approaches and application examples in the study of nanomaterial fate in biological systems will be described to highlight recent successes in the field.

Reversible Diels-Alder Reactions with a Fluorescent Dye on the Surface of Magnetite Nanoparticles.

Diels-Alder reactions on the surface of nanoparticles allow a thermoreversible functionalization of the nanosized building blocks. We report the synthesis of well-defined magnetite nanoparticles by thermal decomposition reaction and their functionalization with maleimide groups. Attachment of these dienophiles was realized by the synthesis of organophosphonate coupling agents and a partial ligand exchange of the original carboxylic acid groups. The functionalized iron oxide particles allow a covalent surface attachment of a furfuryl-functionalized rhodamine B dye by a Diels-Alder reaction at 60 °C. The resulting particles showed the typical fluorescence of rhodamine B. The dye can be cleaved off the particle surface by a retro-Diels-Alder reaction. The study showed that organic functions can be thermoreversibly attached onto inorganic nanoparticles.

Tailored Mesoporous Inorganic Biomaterials: Assembly, Functionalization, and Drug Delivery Engineering.

Infectious or immune diseases have caused serious threat to human health due to their complexity and specificity, and emerging drug delivery systems (DDSs) have evolved into the most promising therapeutic strategy for drug-targeted therapy. Various mesoporous biomaterials are exploited and applied as efficient nanocarriers to loading drugs by virtue of their large surface area, high porosity, and prominent biocompatibility. Nanosized mesoporous nanocarriers show great potential in biomedical research, and it has become the research hotspot in the interdisciplinary field. Herein, recent progress and assembly mechanisms on mesoporous inorganic biomaterials (e.g., silica, carbon, metal oxide) are summarized systematically, and typical functionalization methods (i.e., hybridization, polymerization, and doping) for nanocarriers are also discussed in depth. Particularly, structure-activity relationship and the effect of physicochemical parameters of mesoporous biomaterials, including morphologies (e.g., hollow, core-shell), pore textures (e.g., pore size, pore volume), and surface features (e.g., roughness and hydrophilic/hydrophobic) in DDS application are overviewed and elucidated in detail. As one of the important development directions, advanced stimuli-responsive DDSs (e.g., pH, temperature, redox, ultrasound, light, magnetic field) are highlighted. Finally, the prospect of mesoporous biomaterials in disease therapeutics is stated, and it will open a new spring for the development of mesoporous nanocarriers.

Flower-Like Superstructures: Structural Features, Applications and Future Perspectives.

Mimicking natural objects such as flowers, is an objective of scientists not only because of their attractive appearance, but also to understand the natural phenomena that underpin real world applications such as drug delivery, enzymatic reactions, electronics, and catalysis, to name few. This article reviews the types, preparation methods, and structural features of flower-like structures along with their key applications in various fields. We discuss the various types of flower-like structures composed of inorganic, organic-inorganic hybrid, inorganic-protein, inorganic-enzyme and organic compositions. We also discuss recent development in flower-like structures prepared by self-assembly approaches. Finally, we conclude our review with the future prospects of flower-like micro-structures in key fields, being biomedicine, sensing and catalysis.

Inorganic oxidizer detection from propellants, pyrotechnics, and homemade explosive powders using gradient elution moving boundary electrophoresis.

Advancement in rapid targeted chemical analysis of homemade and improvised explosive devices is critical for the identification of explosives-based hazards and threats. Gradient elution moving boundary electrophoresis (GEMBE), a robust electrokinetic separation technique, was employed for the separation and detection of common inorganic oxidizers from frequently encountered fuel-oxidizer mixtures. The GEMBE system incorporated sample and run buffer reservoirs, a short capillary (5 cm), an applied electric field, and a pressure-driven counterflow. GEMBE provided a separation format that allowed for continuous injection of sample, selectivity of analytes, and no sample cleanup or filtration prior to analysis. Nitrate, chlorate, and perchlorate oxidizers were successfully detected from low explosive propellants (e.g., black powders and black powder substitutes), pyrotechnics (e.g., flash powder), and tertiary explosive mixtures (e.g., ammonium nitrate- and potassium chlorate-based fuel-oxidizer mixtures). Separation of these mixtures exhibited detection without interference from a plethora of additional organic and inorganic fuels, enabled single particle analysis, and demonstrated semiquantitative capabilities. The bulk counterflow successfully excluded difficult components from fouling the capillary, yielding estimated limits of detection down to approximately 10 µmol/L. Finally, nitrate was separated and detected from postblast debris collected and directly analyzed from two nitrate-based charges.