Integrated magneto-plasmonic nanostructures-based immunoassay for galectin-3 detection.

Cardiovascular diseases remain a leading cause of global mortality, highlighting the need for accurate diagnostic tools and the detection of specific cardiac biomarkers. Surface-enhanced Raman scattering (SERS) spectroscopy has proved to be a promising alternative diagnostic tool to detect relevant biomarkers compared to traditional methods. To our knowledge, SERS methodology has never been used to detect galectin-3 (Gal-3), a crucial biomarker for cardiovascular conditions. Our study aimed to develop plasmonic and magneto-plasmonic nanoplatforms for the sensitive immunodetection of Gal-3 using SERS. Spherical gold nanoparticles (AuNPs) were synthesized and functionalized with 11-mercaptoundecanoic acid (MUDA) to enable antibody binding and 4-mercaptobenzoic acid (4MBA) that served as a Raman reporter due to its intense Raman signal. Following bioconjugation with Gal-3 antibody, the AuNPs were employed in the immunodetection of Gal-3 in phosphate-buffer saline (PBS) solution, offering a limit of detection (LOD) of 12.2 ng mL-1 and a working range up to 120 ng mL-1. Furthermore, our SERS-based immunosystem demonstrated selectivity for Gal-3 (40 ng mL-1) in the presence of other biomolecules such as α-amylase, bovine serum albumin and human C-reactive protein. As a proof of concept, we developed magneto-plasmonic nanoparticles composed of silica-coated magnetite decorated with the bioconjugated AuNPs aimed at enhancing the uptake and detection of Gal-3 via SERS coupled with Raman imaging. Our findings underscore the potential of SERS-based techniques for the sensitive and specific detection of biomarkers, holding significant implications for improved diagnosis and surveillance of cardiovascular diseases. Future research will focus on further optimizing these nanoplatforms and their translation into clinical settings.

Resveratrol-Loaded Polydimethylsiloxane-Silica Hybrid Materials: Synthesis, Characterization, and Antitumoral Activity.

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

A Comprehensive Ecotoxicity Study of Molybdenum Disulfide Nanosheets versus Bulk form in Soil Organisms.

The increasing use of molybdenum disulfide (MoS2) nanoparticles (NPs) raises concerns regarding their accumulation in soil ecosystems, with limited studies on their impact on soil organisms. Study aim: To unravel the effects of MoS2 nanosheets (two-dimensional (2D) MoS2 NPs) and bulk MoS2 (156, 313, 625, 1250, 2500 mg/kg) on Enchytraeus crypticus and Folsomia candida. The organisms' survival and avoidance behavior remained unaffected by both forms, while reproduction and DNA integrity were impacted. For E. crypticus, the individual endpoint reproduction was more sensitive, increasing at lower concentrations of bulk MoS2 and decreasing at higher ones and at 625 mg/kg of 2D MoS2 NPs. For F. candida, the molecular endpoint DNA integrity was more impacted: 2500 mg/kg of bulk MoS2 induced DNA damage after 2 days, with all concentrations inducing damage by day 7. 2D MoS2 NPs induced DNA damage at 156 and 2500 mg/kg after 2 days, and at 1250 and 2500 mg/kg after 7 days. Despite affecting the same endpoints, bulk MoS2 induced more effects than 2D MoS2 NPs. Indeed, 2D MoS2 NPs only inhibited E. crypticus reproduction at 625 mg/kg and induced fewer (F. candida) or no effects (E. crypticus) on DNA integrity. This study highlights the different responses of terrestrial organisms to 2D MoS2 NPs versus bulk MoS2, reinforcing the importance of risk assessment when considering both forms.

LSPR-Based Aptasensor for Rapid Urinary Detection of NT-proBNP.

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a myocardial stress biomarker that can be found in serum or plasma, saliva, and urine in the context of cardiovascular disease. In this study, we developed a rapid (~25 min) and straightforward localized surface plasmon resonance (LSPR)-based assay for detecting NT-proBNP in urine. The assay employs citrate-capped gold nanoparticles (AuNPs) and an aptamer specific for NT-proBNP, which initially interacts with NT-proBNP. The remaining unbound aptamer then interacts with the AuNPs, and the addition of NaCl induces the aggregation of the unprotected AuNPs, resulting in a decrease in absorbance at the LSPR band (A521) and an increase in absorbance at 750 nm (A750). The concentration of NT-proBNP showed a linear correlation with the aggregation ratio (A521/A750), and the assay demonstrated a limit of detection (LOD) of 0.303 µg·L-1 and a detection range of 0.566-8 µg·L-1. However, the presence of sulfur-containing proteins in saliva and fetal bovine serum hindered the detection of NT-proBNP in these biofluids. Nevertheless, the assay successfully detected NT-proBNP in diluted urine with an LOD of 0.417 µg·L-1 and a detection range of 0.589-6 µg·L-1. The observed values in urine samples from preterm infants with cardiovascular disease fell within this range, indicating the potential clinical relevance of the assay. The recovery percentages ranged from 92.3 to 116.3%. Overall, our findings suggest that the LSPR-based assay for NT-proBNP detection in urine can be a valuable tool for the diagnosis and treatment of cardiovascular disease.

Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy.

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m2/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.

Gold nanoparticle probes for colorimetric detection of plasma galectin-3: a simple and rapid approach.

Galectin-3 (Gal-3) is a carbohydrate-binding protein associated with the development and progress of heart failure. Here, we report the first colorimetric and low-cost approach for detecting and quantifying Gal-3 using gold nanoparticles (AuNPs) bioconjugated with Gal-3 antibody. The interaction of Gal-3 with the resulting nanoprobes led to a linear response of the absorbance ratio A750nm/A526nm to Gal-3 concentration, accompanied by a change in color intensity. The assay showed a linear optical response even in complex samples, such as saliva and fetal bovine serum (FBS), up to a concentration of 200 µg L-1. The limit of detection (LOD) followed the trend LODPBS (10.0 µg L-1) < LODsaliva (22.6 µg L-1) < LODFBS (25.3 µg L-1). The potential applicability of this method to the analysis of human plasma samples was also demonstrated. Compared to conventional detection techniques, this colorimetric assay provides faster results (∼1 h) and is more cost-effective due to the use of simple and unexpensive equipment. This assay represents an exciting solution for the rapid screening of high risk for rapid progression of heart failure in patient samples (Gal-3 > 25.9 µg L-1).

Corrigendum: Colloidal nanomaterials for water quality improvement and monitoring.

[This corrects the article DOI: 10.3389/fchem.2022.1011186.].

Interaction of Colloidal Gold Nanoparticles with Urine and Saliva Biofluids: An Exploratory Study.

The use of gold nanoparticles for drug delivery, photothermal or photodynamic therapy, and biosensing enhances the demand for knowledge about the protein corona formed on the surface of nanoparticles. In this study, gold nanospheres (AuNSs), gold nanorods (AuNRs), and gold nanoflowers (AuNFs) were incubated with saliva or urine. After the interaction, the surface of gold nanoparticles was investigated using UV-VIS spectroscopy, zeta potential, and dynamic light scattering. The shifting of the localized surface plasmon resonance (LSPR) band, the increase in hydrodynamic diameter, and the changes in the surface charge of nanoparticles indicated the presence of biomolecules on the surface of AuNSs, AuNRs, and AuNFs. The incubation of AuNFs with saliva led to nanoparticle aggregation and minimal protein adsorption. AuNSs and AuNRs incubated in saliva were analyzed through liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the 96 proteins adsorbed on the surface of the gold nanoparticles. Among the 20 most abundant proteins identified, 14 proteins were common in both AuNSs and AuNRs. We hypothesize that the adsorption of these proteins was due to their high sulfur content, allowing for their interaction with gold nanoparticles via the Au-S bond. The presence of distinct proteins on the surface of AuNSs or AuNRs was also investigated and possibly related to the competition between proteins present on the external layers of corona and gold nanoparticle morphology.

Drug Delivery Systems and Flavonoids: Current Knowledge in Melanoma Treatment and Future Perspectives.

Melanoma is an aggressive form of skin cancer with a high prevalence in the population. An early diagnosis is crucial to cure this disease. Still, when this is not possible, combining potent pharmacological agents and effective drug delivery systems is essential to achieve optimal treatment and improve patients' quality of life. Nanotechnology application in biomedical sciences to encapsulate anticancer drugs, including flavonoids, in order to enhance therapeutic efficacy has attracted particular interest. Flavonoids have shown effectiveness against various types of cancers including in melanoma, but they show low aqueous solubility, low stability and very poor oral bioavailability. The utilization of novel drug delivery systems could increase flavonoid bioavailability, thereby potentiating its antitumor effects in melanoma. This review summarizes the potential of different flavonoids in melanoma treatment and the several nanosystems used to improve their biological activity, considering published information that reported improved biological and pharmacological properties of encapsulated flavonoids.

Colloidal nanomaterials for water quality improvement and monitoring.

Water is the most important resource for all kind forms of live. It is a vital resource distributed unequally across different regions of the globe, with populations already living with water scarcity, a situation that is spreading due to the impact of climate change. The reversal of this tendency and the mitigation of its disastrous consequences is a global challenge posed to Humanity, with the scientific community assuming a major obligation for providing solutions based on scientific knowledge. This article reviews literature concerning the development of nanomaterials for water purification technologies, including collaborative scientific research carried out in our laboratory (nanoLAB@UA) framed by the general activities carried out at the CICECO-Aveiro Institute of Materials. Our research carried out in this specific context has been mainly focused on the synthesis and surface chemical modification of nanomaterials, typically of a colloidal nature, as well as on the evaluation of the relevant properties that arise from the envisaged applications of the materials. As such, the research reviewed here has been guided along three thematic lines: 1) magnetic nanosorbents for water treatment technologies, namely by using biocomposites and graphite-like nanoplatelets; 2) nanocomposites for photocatalysis (e.g., TiO2/Fe3O4 and POM supported graphene oxide photocatalysts; photoactive membranes) and 3) nanostructured substrates for contaminant detection using surface enhanced Raman scattering (SERS), namely polymers loaded with Ag/Au colloids and magneto-plasmonic nanostructures. This research is motivated by the firm believe that these nanomaterials have potential for contributing to the solution of environmental problems and, conversely, will not be part of the problem. Therefore, assessment of the impact of nanoengineered materials on eco-systems is important and research in this area has also been developed by collaborative projects involving experts in nanotoxicity. The above topics are reviewed here by presenting a brief conceptual framework together with illustrative case studies, in some cases with original research results, mainly focusing on the chemistry of the nanomaterials investigated for target applications. Finally, near-future developments in this research area are put in perspective, forecasting realistic solutions for the application of colloidal nanoparticles in water cleaning technologies.

Chemical Strategies for Dendritic Magneto-plasmonic Nanostructures Applied to Surface-Enhanced Raman Spectroscopy.

Invited for the cover of this issue is the group of Tito Trindade and colleagues at the University of Aveiro. The image depicts dendritic magneto-plasmonic substrates for surface-enhanced Raman scattering (SERS) detection. Read the full text of the article at 10.1002/chem.202202382.

MoS2 and MoS2 Nanocomposites for Adsorption and Photodegradation of Water Pollutants: A Review.

The need for fresh and conveniently treated water has become a major concern in recent years. Molybdenum disulfide (MoS2) nanomaterials are attracting attention in various fields, such as energy, hydrogen production, and water decontamination. This review provides an overview of the recent developments in MoS2-based nanomaterials for water treatment via adsorption and photodegradation. Primary attention is given to the structure, properties, and major methods for the synthesis and modification of MoS2, aiming for efficient water-contaminant removal. The combination of MoS2 with other components results in nanocomposites that can be separated easily or that present enhanced adsorptive and photocatalytic properties. The performance of these materials in the adsorption of heavy metal ions and organic contaminants, such as dyes and drugs, is reviewed. The review also summarizes current progress in the photocatalytic degradation of various water pollutants, using MoS2-based nanomaterials under UV-VIS light irradiation. MoS2-based materials showed good activity after several reuse cycles and in real water scenarios. Regarding the ecotoxicity of the MoS2, the number of studies is still limited, and more work is needed to effectively evaluate the risks of using this nanomaterial in water treatment.

Chemical Strategies for Dendritic Magneto-plasmonic Nanostructures Applied to Surface-Enhanced Raman Spectroscopy.

Chemical analyses in the field using surface-enhanced Raman scattering (SERS) protocols are expected to be part of several analytical procedures applied to water quality monitoring. To date, these endeavors have been supported by developments in SERS substrate nanofabrication, instrumentation portability, and the internet of things. Here, we report distinct chemical strategies for preparing magneto-plasmonic (Fe3 O4 : Au) colloids, which are relevant in the context of trace-level detection of water contaminants due to their inherent multifunctionality. The main objective of this research is to investigate the role of poly(amidoamine) dendrimers (PAMAMs) in the preparation of SERS substrates integrating both functionalities into single nanostructures. Three chemical routes were investigated to design magneto-plasmonic nanostructures that translate into different ways for assessing SERS detection by using distinct interfaces. Hence, a series of magneto-plasmonic colloids have been characterized and then assessed for their SERS activity by using a model pesticide (thiram) dissolved in aqueous samples.

Label-free dynamic light scattering assay for C-reactive protein detection using magnetic nanoparticles.

In this work, we present a simple method for label-free detection of C-reactive protein (CRP) in diluted saliva samples without the use of specific molecules against CRP. We use the dynamic light scattering (DLS) technique and silica-coated Fe3O4 nanoparticles (∼50 nm in diameter) functionalized with amino carboxylate moieties (Fe3O4@SiO2/COOH) as probes. After contact with the sample, the particles could be easily separated with a handy magnet and redispersed for DLS analysis simply by vortex shaking. The variation of the hydrodynamic diameter of the nanoparticles (Z-average size) could be correlated with the concentration of CRP up to concentrations of 10 mg L-1. The detection limit (LOD) in diluted saliva samples that were spiked with CRP was 0.205 mg L-1, which is below salivary levels of CRP detected in unhealthy individuals. The coefficient of variation was found to be less than 1.5% in the entire detection range. The variation of Z-average size of non-functionalized silica coated nanoparticles (Fe3O4@SiO2) also correlated well with CRP concentration. Nevertheless, the Fe3O4@SiO2/COOH nanoparticles were less susceptible to interference from other biomolecules present in saliva and adsorbed more CRP, indicating higher selectivity toward CRP than nonfunctionalized nanoparticles. This higher affinity was attributed to the chelating interaction between the aminocarboxylate groups of the organosilane N-[3-(trimethoxysilyl)propyl]ethylenediaminetriacetic acid trisodium salt (EDTA-TMS) grafted onto the surface of the Fe3O4@SiO2/COOH nanoparticles and the Ca2+ ions of CRP. LC-MS/MS analyses allowed identification of the proteins adsorbed on the nanoparticles and confirmation of the presence of CRP, which is involved in several biological processes, including immune response, response to stress and transport.

Dendrimer-based magneto-plasmonic nanosorbents for water quality monitoring using surface-enhanced Raman spectroscopy.

In this work, we report the synthesis of magneto-plasmonic dendrimer-based nanosorbents containing Au nanostars and we demonstrate that they can be used as versatile optical sensors for the detection of pesticides in spiked water samples. The magnetic hybrid nanoparticles were obtained by conjugating silica-functionalized G5-NH2 PAMAM dendrimers to silica-coated magnetite cores. The resulting magnetic-PAMAM conjugates were then used to reduce and sequester Au seeds for the subsequent in situ growth of Au nanostars. The dendrimer-based magneto-plasmonic substrates containing the Au anisotropic nanophases were then investigated regarding their ability to monitor water quality through surface-enhanced Raman scattering (SERS) spectroscopy. As a proof-of-concept, the ensuing multifunctional materials were investigated as SERS probing systems to detect dithiocarbamate pesticides (ziram and thiram) dissolved in water samples. It was observed that the magneto-plasmonic hybrid materials enhance the Raman signal of these pesticides under variable operational conditions, suggesting the versatility of these systems for water quality monitoring. Moreover, a detailed analysis of the SERS data was accomplished to predict the adsorption profile of the dithiocarbamate pesticides to the Au surface.

Dendrimer stabilized nanoalloys for inkjet printing of surface-enhanced Raman scattering substrates.

Research on paper substrates prepared by inkjet deposition of metal nanoparticles for sensing applications has become a hot topic in recent years; however, the design of such substrates based on the deposition of alloy nanoparticles remains less explored. Herein, we report for the first time the inkjet printing of dendrimer-stabilized colloidal metal nanoalloys for the preparation of paper substrates for surface-enhanced Raman scattering (SERS) spectroscopy. To this end, nanoassemblies containing variable molar ratios of Au:Ag were prepared in the presence of poly(amidoamine) dendrimer (PAMAM), resulting in plasmonic properties that depend on the chemical composition of the final materials. The dendrimer-stabilized Au:Ag:PAMAM colloids exhibit high colloidal stability, making them suitable for the preparation of inks for long-term use in inkjet printing of paper substrates. Moreover, the pre-treatment of paper with a polystyrene (PS) aqueous emulsion resulted in hydrophobic substrates with improved SERS sensitivity, as illustrated in the analytical detection of tetramethylthiuram disulfide (thiram pesticide) dissolved in aqueous solutions. We suggest that the interactions established between the two polymers (PAMAM and PS) in an interface region over the cellulosic fibres, resulted in more exposed metallic surfaces for the adsorption of the analyte molecules. The resulting hydrophobic substrates show long-term plasmonic stability with high SERS signal retention for at least ninety days.

Silica-Based Nanomaterials for Diabetes Mellitus Treatment.

Diabetes mellitus, a chronic metabolic disease with an alarming global prevalence, is associated with several serious health threats, including cardiovascular diseases. Current diabetes treatments have several limitations and disadvantages, creating the need for new effective formulations to combat this disease and its associated complications. This motivated the development of therapeutic strategies to overcome some of these limitations, such as low therapeutic drug bioavailability or poor compliance of patients with current therapeutic methodologies. Taking advantage of silica nanoparticle characteristics such as tuneable particle and pore size, surface chemistry and biocompatibility, silica-based nanocarriers have been developed with the potential to treat diabetes and regulate blood glucose concentration. This review discusses the main topics in the field, such as oral administration of insulin, glucose-responsive devices and innovative administration routes.

Gold nanoparticles-based assays for biodetection in urine.

Urine is a biofluid easy to collect through a non-invasive technique that allows collecting a large volume of sample. The use of urine for disease diagnosis is not yet well explored. However, it has gained attention over the last three years. It has been applied in the diagnosis of several illnesses such as kidney disease, bladder cancer, prostate cancer and cardiovascular diseases. In the last decade, gold nanoparticles (Au NPs) have attracted attention in biosensors' development for the diagnosis of diseases due to their electrical and optical properties, ability to conjugate with biomolecules, high sensitivity, and selectivity. Therefore, this article aims to present a comprehensive view of state of the art on the advances made in the quantification of analytes in urinary samples using AuNPs based assays, with a focus on protein analysis. The type of diagnosis methods, the Au NPs synthesis approaches and the strategies for surface modification aiming at selectivity towards the different targets are highlighted.

Encapsulation and Enhanced Release of Resveratrol from Mesoporous Silica Nanoparticles for Melanoma Therapy.

Chemotherapy has limited success in the treatment of malignant melanoma due to fast development of drug resistance and the low bioavailability of chemotherapeutic drugs. Resveratrol (RES) is a natural polyphenol with recognized preventive and therapeutic anti-cancer properties. However, poor RES solubility hampers its bioactivity, thus creating a demand for suitable drug delivery systems to improve it. This work aimed to assess the potential of RES-loaded mesoporous silica nanoparticles (MSNs) for human melanoma treatment. RES was efficiently loaded (efficiency > 93%) onto spheroidal (size~60 nm) MSNs. The encapsulation promoted the amorphization of RES and enhanced the release in vitro compared to non-encapsulated RES. The RES release was pH-dependent and markedly faster at pH 5.2 (acid environment in some tumorous tissues) than at pH 7.4 in both encapsulated and bulk forms. The RES release from loaded MSNs was gradual with time, without a burst effect, and well-described by the Weibull model. In vitro cytotoxicity studies on human A375 and MNT-1 melanoma cellular cultures showed a decrease in the cell viability with increasing concentration of RES-loaded MSNs, indicating the potent action of the released RES in both cell lines. The amelanotic cell line A375 was more sensitive to RES concentration than the melanotic MNT-1 cells.

An integrated approach to assess the sublethal effects of colloidal gold nanorods in tadpoles of Xenopus laevis.

Gold nanorods (AuNR) have been explored for many applications, including innovative nanomedicines, which also might contribute to its increase in the environment, namely due to inadequate disposable of wastes into aquatic environments. Early-life stages of amphibians are usually aquatic and sensitive to chemical contamination. Accordingly, this study aimed to determine the sublethal effects of CTAB functionalized AuNR on Xenopus laevis tadpoles. As such, tadpoles were exposed to serial concentrations of AuNR for 72 h. A reduction in the rate of feeding (EC50 = 4 µg.L-1), snout to vent growth (EC50 = 5 µg.L-1) and weight gain (EC50 = 6 µg.L-1), was observed for AuNR-exposed tadpoles. Also, tadpoles actively avoided concentrations ≥ 4 µg.L-1 of AuNR, after 12 h of exposure. At the biochemical level, AuNR caused impairments in antioxidant and nervous system related enzymes. Exposure to CTAB alone caused a high mortality. Results indicated that CTAB functionalized AuNR may induce several sublethal effects that may compromise the organism's fitness. Avoidance behavior (which corresponds to the disappearance of organisms, thus, similar to their death), observed at concentrations matching those inducing sublethal effects, suggest that it should be considered in the risk assessment for amphibians.