Enhancing Phototoxicity in Human Colorectal Tumor Cells Through Nanoarchitectonics for Synergistic Photothermal and Photodynamic Therapies.

Phototherapies are promising for noninvasive treatment of aggressive tumors, especially when combining heat induction and oxidative processes. Herein, we show enhanced phototoxicity of gold shell-isolated nanorods conjugated with toluidine blue-O (AuSHINRs@TBO) against human colorectal tumor cells (Caco-2) with synergic effects of photothermal (PTT) and photodynamic therapies (PDT). Mitochondrial metabolic activity tests (MTT) performed on Caco-2 cell cultures indicated a photothermal effect from AuSHINRs owing to enhanced light absorption from the localized surface plasmon resonance (LSPR). The phototoxicity against Caco-2 cells was further increased with AuSHINRs@TBO where oxidative processes, such as hydroperoxidation, were also present, leading to a cell viability reduction from 85.5 to 39.0%. The molecular-level mechanisms responsible for these effects were investigated on bioinspired tumor membranes using Langmuir monolayers of Caco-2 lipid extract. Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) revealed that the AuSHINRs@TBO incorporation is due to attractive electrostatic interactions with negatively charged groups of the Caco-2 lipid extract, resulting in the expansion of surface pressure isotherms. Upon irradiation, Caco-2 lipid extract monolayers containing AuSHINRs@TBO (1:1 v/v) exhibited ca. 1.0% increase in surface area. This is attributed to the generation of reactive oxygen species (ROS) and their interaction with Caco-2 lipid extract monolayers, leading to hydroperoxide formation. The oxidative effects are facilitated by AuSHINRs@TBO penetration into the polar groups of the extract, allowing oxidative reactions with carbon chain unsaturations. These mechanisms are consistent with findings from confocal fluorescence microscopy, where the Caco-2 plasma membrane was the primary site of the cell death induction process.

Brownian Motion Governs the Plasmonic Enhancement of Colloidal Upconverting Nanoparticles.

Upconverting nanoparticles are essential in modern photonics due to their ability to convert infrared light to visible light. Despite their significance, they exhibit limited brightness, a key drawback that can be addressed by combining them with plasmonic nanoparticles. Plasmon-enhanced upconversion has been widely demonstrated in dry environments, where upconverting nanoparticles are immobilized, but constitutes a challenge in liquid media where Brownian motion competes against immobilization. This study employs optical tweezers for the three-dimensional manipulation of an individual upconverting nanoparticle, enabling the exploration of plasmon-enhanced upconversion luminescence in water. Contrary to expectation, experiments reveal a long-range (micrometer scale) and moderate (20%) enhancement in upconversion luminescence due to the plasmonic resonances of gold nanostructures. Comparison between experiments and numerical simulations evidences the key role of Brownian motion. It is demonstrated how the three-dimensional Brownian fluctuations of the upconverting nanoparticle lead to an "average effect" that explains the magnitude and spatial extension of luminescence enhancement.

Sticky Multicolor Mechanochromic Labels.

Sticky-colored labels are an efficient way to communicate visual information. However, most labels are static. Here, we propose a new category of dynamic sticky labels that change structural colors when stretched. The sticky mechanochromic labels can be pasted on flexible surfaces such as fabric and rubber or even on brittle materials. To enhance their applicability, we demonstrate a simple method for imprinting structural color patterns that are either always visible or reversibly revealed or concealed upon mechanical deformation. The mechanochromic patterns are imprinted with a photomask during the ultraviolet (UV) cross-linking of acrylate-terminated cholesteric liquid crystal oligomers in a single step at room temperature. The photomask locally controls the cross-linking degree and volumetric response of the cholesteric liquid crystal elastomers (CLCEs). A nonuniform thickness change induced by the Poisson's ratio contrast between the pattern and the surrounding background might lead to a color-separation effect. Our sticky multicolor mechanochromic labels may be utilized in stress-strain sensing, building environments, smart clothing, security labels, and decoration.

Core-Shell Nanocables Decorated with Carbon Spherical Shells and Silver Nanoparticles for Sensing Ethinylestradiol Hormone in Water Sources and Pills.

The selective, rapid detection of low levels of hormones in drinking water and foodstuffs requires materials suitable for inexpensive sensing platforms. We report on core-shell Ag@C nanocables (NCs) decorated with carbon spherical shells (CSSs) and silver nanoparticles (AgNPs) by using a hydrothermal green approach. Sensors were fabricated with homogeneous, porous films on screen-printed electrodes, which comprised a 115 nm silver core covered by a 122 nm thick carbon layer and CSSs with 168 nm in diameter. NCs and CSSs were also decorated with 10-25 nm AgNPs. The NC/CSS/AgNP sensor was used to detect ethinylestradiol using square wave voltammetry in 0.1 M phosphate buffer (pH 7.0) over the 1.0-10.0 µM linear range with a detection limit of 0.76 µM. The sensor was then applied to detect ethinylestradiol in tap water samples and a contraceptive pill with recovery percentages between 93 and 101%. The high performance in terms of sensitivity and selectivity for hormones is attributed to the synergy between the carbon nanomaterials and AgNPs, which not only increased the sensor surface area and provided sites for electron exchange but also imparted an increased surface area.

Magnetochiroptical nanocavities in hyperbolic metamaterials enable sensing down to the few-molecule level.

In this work, we combine the concepts of magnetic circular dichroism, nanocavities, and magneto-optical hyperbolic metamaterials (MO-HMMs) to demonstrate an approach for sensing down to a few molecules. Our proposal comprises a multilayer MO-HMM with a square, two-dimensional arrangement of nanocavities. The magnetization of the system is considered in polar configuration, i.e., in the plane of polarization and perpendicular to the plane of the multilayer structure. This allows for magneto-optical chirality to be induced through the polar magneto-optical Kerr effect, which is exhibited by reflected light from the nanostructure. Numerical analyses under the magnetization saturation condition indicate that magnetic circular dichroism peaks can be used instead of reflectance dips to monitor refractive index changes in the analyte region. Significantly, we obtained a relatively high sensitivity value of S = 40 nm/RIU for the case where refractive index changes are limited to the volume inside nanocavities, i.e., in the limit of a few molecules (or ultralow concentrations), while a very large sensitivity of S = 532 nm/RIU is calculated for the analyte region distributed along the entire superstrate layer.

Revisiting the conformational transition model for the pH dependence of BSA structure using photoluminescence, circular dichroism, and ellipsometric Raman spectroscopy.

Changes in pH affect metabolic pathways, primarily by modulating enzyme conformations, which is why a detailed analysis of pH-driven conformational transitions is required to understand the underlying biochemistry of diseases and biological organisms. In this work, we examined the pH-driven conformational dynamics of Bovine Serum Albumin (BSA), within the framework of the Foster Model. Circular Dichroism and Raman Optical Activity showed the conversion of helical into ß-rich structures in the acid and basic regions, while an opening of BSA tertiary structure was shown by the upsurging of accessibility of ANS-BSA binding sites and the increasing of random contributions at regions F and B. We could then revisit the Foster Model by introducing two additional intermediate conformational states and structural reorganization at extreme pH values. This expanded model opens up new possibilities concerning protein-molecule interactions, promising far-reaching implications for fields such as drug design and biomaterials.

In situ interaction between the hormone 17α-ethynylestradiol and the liquid-ordered phase composed of the lipid rafts sphingomyelin and cholesterol.

Hormone treatments are frequently associated with cardiovascular diseases and cancers in women. Additionally, the detrimental effects of their presence as contaminants in water remain a concern. The transport of hormones through cell membranes is essential for their biological action, but investigating cell permeability is challenging owing to the experimental difficulty in dealing with whole cells. In this paper, we study the interaction of the synthetic hormone 17α-ethynylestradiol (EE2) with membrane models containing the key raft components sphingomyelin (SM) and cholesterol (Chol). The models consisted of Langmuir monolayers and giant unilamellar vesicles (GUVs) that represent bilayers. EE2 induced expansion of SM monolayers upon interacting with the non-hydrated amide group of SM head, but it had practically no effect on SM GUVs because these group are not available for interaction in bilayers. In contrast, EE2 interacted with hydrated phosphate group (PO2-) and amide group of SM/Chol mixture monolayer, which could explain the loss in phase contrast of liquid-ordered GUVs suggesting pore formation. A comparison with reported EE2 effects on GUVs in the fluid phase, for which no loss in phase contrast was observed, indicates that the liquid-ordered phase consisting of lipid rafts is relevant to be associated with the changes on cell permeability caused by the hormones.

Quaternized chitosan (nano)fibers: A journey from preparation to high performance applications.

The industrial production of chitosan, initiated over 50 years ago, has transformed its application across diverse industries, agriculture, and medicine. To enhance its properties, numerous chitosan derivatives have been synthesized. The quaternization of chitosan has proven beneficial, as it not only enhances its properties but also imparts water solubility, expanding its potential for a wider range of applications. Specifically, the utilization of quaternized chitosan-based nanofibers has leveraged the synergistic benefits of quaternized chitosan (including hydrophilicity, bioadhesiveness, antimicrobial, antioxidant, hemostatic, and antiviral activities, as well as ionic conductivity) in combination with the distinctive characteristics of nanofibers (such as a high aspect ratio and 3D architecture). This combination has permitted numerous possibilities, spanning from wound dressings, air and water filters, drug delivery scaffolds, antimicrobial textiles, to energy storage systems and alkaline fuel cells. In this comprehensive review, we examine the preparation methods, properties, and applications of various composite fibers containing quaternized chitosan. The advantages and disadvantages of each method and composition are meticulously summarized, while relevant diagrams and figures illustrate the key findings.

Network Analysis and Natural Language Processing to Obtain a Landscape of the Scientific Literature on Materials Applications.

Recent progress in natural language processing (NLP) enables mining the literature in various tasks akin to knowledge discovery. Obtaining an updated birds-eye view of key research topics and their evolution in a vast, dynamic field such as materials science is challenging even for experienced researchers. In this Perspective paper, we present a landscape of the area of applied materials in selected representative journals based on a combination of methods from network science and simple NLP strategies. We found a predominance of energy-related materials, e.g., for batteries and catalysis, organic electronics, which include flexible sensors and flexible electronics, and nanomedicine with various topics of materials used in diagnosis and therapy. As for the impact calculated through standard metrics of impact factor, energy-related materials and organic electronics are again top of the list across different journals, while work in nanomedicine has been found to have a lower impact in the journals analyzed. The adequacy of the approach to identify key research topics in materials applications was verified indirectly by comparing the topics identified in journals with diverse scopes, including journals that are not specific to materials. The approach can be employed to obtain a fast overview of a given field from the papers published in related scientific journals, which can be adapted or extended to any research area.

Incorporation of acridine orange and methylene blue in Langmuir monolayers mimicking releasing nanostructures.

The efficiency of methylene blue (MB) and acridine orange (AO) for photodynamic therapy (PDT) is increased if encapsulated in liposomes. In this paper we determine the molecular-level interactions between MB or AO and mixed monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) and cholesterol (CHOL) using surface pressure isotherms and polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). To increase liposome stability, the effects from adding the surfactants Span® 80 and sodium cholate were also studied. Both MB and AO induce an expansion in the mixed monolayer, but this expansion is less significant in the presence of either Span® 80 or sodium cholate. The action of AO and MB occurred via coupling with phosphate groups of DPPC or DPPG. However, the levels of chain ordering and hydration of carbonyl and phosphate in headgroups depended on the photosensitizer and on the presence of Span® 80 or sodium cholate. From the PM-IRRAS spectra, we inferred that incorporation of MB and AO increased hydration of the monolayer headgroup, except for the case of the monolayer containing sodium cholate. This variability in behaviour offers an opportunity to tune the incorporation of AO and MB into liposomes which could be exploited in the release necessary for PDT.

Nanoarchitectonic E-Tongue of Electrospun Zein/Curcumin Carbon Dots for Detecting Staphylococcus aureusin Milk.

We report a nanoarchitectonic electronic tongue made with flexible electrodes coated with curcumin carbon dots and zein electrospun nanofibers, which could detect Staphylococcus aureus(S. aureus) in milk using electrical impedance spectroscopy. Electronic tongues are based on the global selectivity concept in which the electrical responses of distinct sensing units are combined to provide a unique pattern, which in this case allowed the detection of S. aureus through non-specific interactions. The electronic tongue used here comprised 3 sensors with electrodes coated with zein nanofibers, carbon dots, and carbon dots with zein nanofibers. The capacitance data obtained with the three sensors were processed with a multidimensional projection technique referred to as interactive document mapping (IDMAP) and analyzed using the machine learning-based concept of multidimensional calibration space (MCS). The concentration of S. aureus could be determined with the sensing units, especially with the one containing zein as the limit of detection was 0.83 CFU/mL (CFU stands for colony-forming unit). This high sensitivity is attributed to molecular-level interactions between the protein zein and C-H groups in S. aureus according to polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS) data. Using machine learning and IDMAP, we demonstrated the selectivity of the electronic tongue in distinguishing milk samples from mastitis-infected cows from milk collected from healthy cows, and from milk spiked with possible interferents. Calibration of the electronic tongue can also be reached with the MCS concept employing decision tree algorithms, with an 80.1% accuracy in the diagnosis of mastitis. The low-cost electronic tongue presented here may be exploited in diagnosing mastitis at early stages, with tests performed in the farms without requiring specialized laboratories or personnel.

Geometry Optimization for Miniaturized Thermoelectric Generators.

Thermoelectric materials capable of converting heat into electrical energy are used in sustainable electric generators, whose efficiency has been normally increased with incorporation of new materials with high figure of merit (ZT) values. Because the performance of these thermoelectric generators (TEGs) also depends on device geometry, in this study we employ the finite element method to determine optimized geometries for highly efficient miniaturized TEGs. We investigated devices with similar fill factors but with different thermoelectric leg geometries (filled and hollow). Our results show that devices with legs of hollow geometry are more efficient than those with filled geometry for the same length and cross-sectional area of thermoelectric legs. This behavior was observed for thermoelectric leg lengths smaller than 0.1 mm, where the leg shape causes a significant difference in temperature distribution along the device. It was found that for reaching highly efficient miniaturized TEGs, one has to consider the leg geometry in addition to the thermal conductivity.

Magnetoplasmonic Nanoantennas for On-Chip Reconfigurable Optical Wireless Communications.

On-chip wireless communications require optical nanoantennas with dynamically tunable radiation patterns, which may allow for higher integration with multiple nanoantennas instead of two fixed nanoantennas in existing approaches. In this paper, we introduce a concept to enable active manipulation of radiated beam steering using applied magnetic fields. The proposed system consists of a highly directive Yagi-Uda-like arrangement of magnetoplasmonic nanoribs made of Co6Ag94 and immersed in SiO2. Numerical demonstration of the tilting of the radiated beam from the nanoantenna on its plane is provided with full-wave electromagnetic simulations using the finite element method. The tilt direction of the radiated beam can be changed by reversing the magnetization direction, while the conventional plasmonic nanoantenna pattern is recovered by demagnetizing the system. The geometry of the nanoantenna can be tailored to work at optical or infrared wavelengths, but a proof of concept for λ = 700 nm is conducted for taking advantage of the high magneto-optical activity of Co6Ag94. The design was based on experimental data for materials that can be fabricated via nanolithography, thus permitting magnetically on-chip reconfigurable optical wireless communications.

Optimized paper-based electrochemical sensors treated in acidic media to detect carbendazim on the skin of apple and cabbage.

Wearable sensors such as those made with paper are needed for non-destructive routine analysis of pesticides on plants, fruits, and vegetables. Herein we report on electrochemical sensors made with screen-printed carbon electrodes on kraft and parchment papers to detect the fungicide carbendazim. A systematic optimization was performed to find that electrochemical sensors on kraft paper treated in an acidic medium led to the highest performance, with a detection limit of 0.06 µM for carbendazim. The enhanced sensitivity for this sensor was attributed to the porous nature of kraft paper, which allowed for a large electrode surface area, and to the carboxylic groups formed during electrochemical activation. As a proof-of-concept, the electrochemical sensor attached to the skin of apple and cabbage was used to detect carbendazim with the same performance as the gold standard method, thus demonstrating that the sensor can be used in the farm and on supermarket shelves.

Wearable potentiometric biosensor for analysis of urea in sweat.

Herein, we introduce wearable potentiometric biosensors on screen-printed carbon electrodes (SPCEs) for on-body and on-site monitoring of urea in sweat. The biosensor architecture was judiciously designed to detect urea at different pHs and incorporate a pH sensor, thus containing polyaniline ink, urease bioink and a polyvinylchloride membrane. Urea detection could be performed in the wide range from 5 to 200 mM at pH 7.0, encompassing urea levels in human sweat. The biosensor response was fast (incubation time 5 min), with no interference from other substances in sweat. Reliable urea detection could be done in undiluted human sweat with a skin-worn flexible device using the pH correction strategy afforded by the pH sensor. The performance of the epidermal biosensor was not affected by severe bending strains. The feasibility of mass production was demonstrated by fabricating epidermal flexible biosensors using slot-die coating with a roll-to-roll technique.

Colorimetric Detection of SARS-CoV-2 Using Plasmonic Biosensors and Smartphones.

Low-cost, instrument-free colorimetric tests were developed to detect SARS-CoV-2 using plasmonic biosensors with Au nanoparticles functionalized with polyclonal antibodies (f-AuNPs). Intense color changes were noted with the naked eye owing to plasmon coupling when f-AuNPs form clusters on the virus, with high sensitivity and a detection limit of 0.28 PFU mL-1 (PFU stands for plaque-forming units) in human saliva. Plasmon coupling was corroborated with computer simulations using the finite-difference time-domain (FDTD) method. The strategies based on preparing plasmonic biosensors with f-AuNPs are robust to permit SARS-CoV-2 detection via dynamic light scattering and UV-vis spectroscopy without interference from other viruses, such as influenza and dengue viruses. The diagnosis was made with a smartphone app after processing the images collected from the smartphone camera, measuring the concentration of SARS-CoV-2. Both image processing and machine learning algorithms were found to provide COVID-19 diagnosis with 100% accuracy for saliva samples. In subsidiary experiments, we observed that the biosensor could be used to detect the virus in river waters without pretreatment. With fast responses and requiring small sample amounts (only 20 µL), these colorimetric tests can be deployed in any location within the point-of-care diagnosis paradigm for epidemiological control.

Influence of cytochrome P450 3A4 and membrane lipid composition on doxorubicin activity.

Drug resistance is known to depend on the interactions with cell membranes and other molecules such as human cytochromes P450 (CYPs) which are anchored on the endoplasmic reticulum (ER) membrane and involved in the metabolism of anticancer drugs. In this study, we determined the influence from cytochrome P450 3A4 (CYP3A4) on the interaction between the drug doxorubicin (DOX) and Langmuir monolayers mimicking cell membranes. The lipid composition was varied by changing the relative concentrations of cholesterol (Chol), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and L-α-phosphatidylinositol (PI). Three compositions were studied in detail which represented a healthy cell membrane and cancerous cell membranes. DOX induced an expansion in the surface pressure isotherms for all monolayers, with stronger effect for the composition of cancerous cell with a high Chol content, thus confirming the relevance of lipid composition. This effect decreased considerably when CYP3A4 was incorporated with the formation of CYP3A4-DOX complexes, according to results from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS) measurements. Taken together, these results support the hypothesis of CYP3A4 being involved in drug resistance, which may be exploited to design strategies to enhance chemotherapy efficacy.

Three-Dimensional Printing and Its Potential to Develop Sensors for Cancer with Improved Performance.

Cancer is the second leading cause of death globally and early diagnosis is the best strategy to reduce mortality risk. Biosensors to detect cancer biomarkers are based on various principles of detection, including electrochemical, optical, electrical, and mechanical measurements. Despite the advances in the identification of biomarkers and the conventional 2D manufacturing processes, detection methods for cancers still require improvements in terms of selectivity and sensitivity, especially for point-of-care diagnosis. Three-dimensional printing may offer the features to produce complex geometries in the design of high-precision, low-cost sensors. Three-dimensional printing, also known as additive manufacturing, allows for the production of sensitive, user-friendly, and semi-automated sensors, whose composition, geometry, and functionality can be controlled. This paper reviews the recent use of 3D printing in biosensors for cancer diagnosis, highlighting the main advantages and advances achieved with this technology. Additionally, the challenges in 3D printing technology for the mass production of high-performance biosensors for cancer diagnosis are addressed.

Bactericidal activity of Ag4V2O7/ß-AgVO3 heterostructures against antibiotic-resistant Klebsiella pneumoniae.

Although Ag-based materials are efficient against antibiotic-resistant bacteria, their high toxicity to living organisms represents a major challenge for obtaining useful products. In this work, we report the bactericidal activity of Ag4V2O7/ß-AgVO3 heterostructures, which proved to be effective against Klebsiella pneumoniae (ATCC 1706, a standard strain; A54970, a multidrug-resistant carbapenemase (KPC)-producing strain; A34057, a multidrug-resistant strain capable of producing extended spectrum beta-lactamases (ESBL); and a community-isolated strain, A58240) at minimum inhibitory concentrations (MIC) as low as 62.5 µg/mL. This activity is higher than that reported for the individual silver vanadates (Ag4V2O7 or ß-AgVO3) owing to the synergistic interactions between both semiconductors. However, the most efficient heterostructure was found to be toxic to mouse 3 T3 fibroblasts and to L. sativa and C. sativus seeds, as indicated by MTT ((4,5 - dimethylthiazol -2yl) 2,5 -diphenylbromide), neutral red assays and germination index measurements. The antimicrobial, phytotoxic and cytotoxic activities were all associated with an efficient generation of reactive oxygen species (ROS) in the heterostructure, especially OH and O2- radicals. The ROS production by Ag4V2O7/ß-AgVO3 heterostructures was measured through photodegradation studies with Rhodamine B. While the bactericidal activity of the heterostructures is promising, especially when compared to Ag-based materials, their use in practical applications will require encapsulation either to avoid leaching or to mitigate their toxicity to humans, animals and plants.

Materials Discovery With Machine Learning and Knowledge Discovery.

Machine learning and other artificial intelligence methods are gaining increasing prominence in chemistry and materials sciences, especially for materials design and discovery, and in data analysis of results generated by sensors and biosensors. In this paper, we present a perspective on this current use of machine learning, and discuss the prospects of the future impact of extending the use of machine learning to encompass knowledge discovery as an essential step towards a new paradigm of machine-generated knowledge. The reasons why results so far have been limited are given with a discussion of the limitations of machine learning in tasks requiring interpretation. Also discussed is the need to adapt the training of students and scientists in chemistry and materials sciences, to better explore the potential of artificial intelligence capabilities.