Electrochemical Sensing Device for Carboplatin Monitoring in Proof-of-Concept Drug Delivery Nanosystems.

(1) Background: Carboplatin (CBP) is a chemotherapeutic drug widely used in the treatment of a variety of cancers. Despite its efficiency, CBP is associated with side effects that greatly limit its clinical use. To mitigate these effects, CBP can be encapsulated in targeted delivery systems, such as liposomes. Ensuring the adequate loading and release of CBP from these carriers requires strict control in pharmaceutical formulation development, demanding modern, rapid, and robust analytical methods. The aim of this study was the development of a sensor for the fast and accurate quantification of CBP and its application on proof-of-concept CBP-loaded nanosomes. (2) Methods: Screen-printed electrodes were obtained in-lab and the electrochemical behavior of CBP was tested on the obtained electrodes. (3) Results: The in-lab screen-printed electrodes demonstrated superior properties compared to commercial ones. The novel sensors demonstrated accurate detection of CBP on a dynamic range from 5 to 500 µg/mL (13.5-1350 µM). The method was successfully applied on CBP loaded and released from nanosomes, with strong correlations with a spectrophotometric method used as control. (4) Conclusions: This study demonstrates the viability of electrochemical techniques as alternative options during the initial phases of pharmaceutical formulation development.

A review on magnetic beads-based SELEX technologies: Applications from small to large target molecules.

This review summarizes the stepwise strategy and key points for magnetic beads (MBs)-based aptamer selection which is suitable for isolating aptamers against small and large molecules via systematic evolution of ligands by exponential enrichment (SELEX). Particularities, if any, are discussed according to the target size. Examples targeting small molecules (<1000 Da) such as xenobiotics, toxins, pesticides, herbicides, illegal additives, hormones, and large targets such as proteins (biomarkers, pathogens) are discussed and presented in tabular formats. Of special interest are the latest advances in more efficient alternatives, which are based on novel instrumentation, materials or microelectronics, such as fluorescence MBs-SELEX or microfluidic chip system-assisted MBs-SELEX. Limitations and perspectives of MBs-SELEX are also reviewed. Taken together, this review aims to provide practical insights into MBs-SELEX technologies and their ability to screen multiple potential aptamers against targets from small to large molecules.

Electrochemically assisted DNA and thioaromatic assembly as sensing and antifouling interface for food allergens.

Food allergies have become a global issue and are estimated to affect approximately 220 million people worldwide. Allergy to peanuts can easily become life-threatening and induce anaphylactic reactions. Mislabeling and cross-contamination during food processing can occur in the frame of world population growth and pose a serious health issue. As the mandatory allergen list is not uniform worldwide, the development of routine analytical strategies with high specificity and sensitivity is a demanding task to aid in the rapid identification of allergenic foods. In this work, an electrochemical aptasensor for Ara h1 peanut allergen was developed by immobilizing the specific aptamer by the inserting method. First, a layer of p-aminothiophenol (p-ATP) was immobilized on the gold surface of screen-printed electrodes (GSPE) to improve the aptamer insertion and reduce the fouling effects at the electrode surface. The grafting of the p-ATP and Ara h1 aptamer on the GSPE surface was monitored by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The resulting disposable aptasensor allowed for indirect electrochemical detection of Ara h1 protein in the presence of 5 mM ferro/ferricyanide as a redox probe. The electrochemical response upon aptamer-target interaction was monitored in the concentration range 1-250 nM, and two limits of detection in the nanomolar range were estimated based on DPV (2.78 nM Ara h1) and EIS (0.82 nM Ara h1) measurements. The aptasensor was successfully applied to real sample analysis.

Unrevealing the connection between real sample analysis and analytical method. The case of cytokines.

Cytokines are compounds that belong to a special class of signaling biomolecules that are responsible for several functions in the human body, being involved in cell growth, inflammatory, and neoplastic processes. Thus, they represent valuable biomarkers for diagnosing and drug therapy monitoring certain medical conditions. Because cytokines are secreted in the human body, they can be detected in both conventional samples, such as blood or urine, but also in samples less used in medical practice such as sweat or saliva. As the importance of cytokines was identified, various analytical methods for their determination in biological fluids were reported. The gold standard in cytokine detection is considered the enzyme-linked immunosorbent assay method and the most recent ones have been considered and compared in this study. It is known that the conventional methods are accompanied by a few disadvantages that new methods of analysis, especially electrochemical sensors, are trying to overcome. Electrochemical sensors proved to be suited for the elaboration of integrated, portable, and wearable sensing devices, which could also facilitate cytokines determination in medical practice.

Design of smart nanoparticles for the electrochemical detection of 3,4-methylenedioxymethamphetamine to allow in field screening by law enforcement officers.

A portable and highly sensitive sensor was designed for the specific detection of 3,4-methyl-enedioxy-methamphetamine (MDMA), in a range of field-testing situations. The sensor can detect MDMA in street samples, even when other controlled substances drugs, or adulterants are present. In this work, we report for the first time a sensor using electroactive molecularly imprinted polymer nanoparticles computationally designed to recognize MDMA and then produced using solid phase synthesis. A composite comprising chitosan, reduced graphene oxide, and molecularly imprinted polymer nanoparticles synthesized for MDMA for the first time was immobilized on screen-printed carbon electrodes. The sensors displayed a satisfactory sensitivity (106.8 nA × µM-1 ), limit of detection (1.6 nM; 0.31 ng/mL), and recoveries (92-99%). The accuracy of the results was confirmed through validation using Ultra-High Performance Liquid Chromatography coupled with tandem Mass Spectrometry (UPLC-MS/MS). This technology could be used in forensic analysis and make it possible to selectively detect MDMA in street samples.

Discovery of New Hydrazone-Thiazole Polyphenolic Antioxidants through Computer-Aided Design and In Vitro Experimental Validation.

Oxidative stress is linked to a series of diseases; therefore, the development of efficient antioxidants might be beneficial in preventing or ameliorating these conditions. Based on the structure of a previously reported compound with good antioxidant properties and on computational studies, we designed several catechol derivatives with enhanced antioxidant potential. The compounds were synthesized and physicochemically characterized, and their antioxidant activity was assessed through different antiradical, electron transfer and metal ions chelation assays, their electrochemical behavior and cytotoxicity were studied. The results obtained in the in vitro experiments correlated very well with the in silico studies; all final compounds presented very good antioxidant properties, generally superior to those of the reference compounds used. Similarly, the results obtained from studying the compounds' electrochemical behavior were in good agreement with the results of the antioxidant activity evaluation assays. Regarding the compounds' cytotoxicity, compound 7b had a dose-dependent inhibitory effect against all cell lines. In conclusion, through computer-aided design, we developed several catechol thiazolyl-hydrazones with excellent antioxidant properties, of which compound 7b, with two catechol moieties in its structure, exhibited the best antioxidant activity.

Forensic Analysis of Synthetic Cathinones on Nanomaterials-Based Platforms: Chemometric-Assisted Voltametric and UPLC-MS/MS Investigation.

Synthetic cathinones (SCs) are a group of new psychoactive substances often referred to as "legal highs" or "bath salts", being characterized by a dynamic change, new compounds continuously emerging on the market. This creates a lack of fast screening tests, making SCs a constant concern for law enforcement agencies. Herein, we present a fast and simple method for the detection of four SCs (alpha-pyrrolidinovalerophenone, N-ethylhexedrone, 4-chloroethcathinone, and 3-chloromethcathinone) based on their electrochemical profiles in a decentralized manner. In this regard, the voltametric characterization of the SCs was performed by cyclic and square wave voltammetry. The elucidation of the SCs redox pathways was successfully achieved using liquid chromatography coupled to (tandem) mass spectrometry. For the rational identification of the ideal experimental conditions, chemometric data processing was employed, considering two critical qualitative and quantitative variables: the type of the electrochemical platform and the pH of the electrolyte. The analytical figures of merit were determined on standard working solutions using the optimized method, which exhibited wide linear ranges and LODs suitable for confiscated sample screening. Finally, the performance of the method was evaluated on real confiscated samples, the resulting validation parameters being similar to those obtained with another portable device (i.e., Raman spectrometer).

Staphylococcus aureus - Review on potential targets for sensors development.

Staphylococcus aureus (S. aureus) is accountable for a wide variety of clinical disease with a high rate of morbidity and mortality around the globe. It has a leading place into the ESKAPE group that includes six pathogens and exhibit multidrug resistance and are the major cause of healthcare associated infections: Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. A critical overview regarding the development of sensors for both S. aureus and his, more dangerous alter ego, Methicillin-resistant S. aureus (MRSA) was presented focusing on the bacteria targets starting with the detection of the whole cell, up to specific wall components, toxins or other virulence factors. The literature data was systematically assessed having in sight the design of the sensing platforms, the analytical performances, and possible courses of action to be implemented in real practice as point-of-care (POC) devices. Moreover, a distinct section was dedicated to commercially available devices and out of the box approaches, namely the use of bacteriophages as an alternative to antimicrobial therapy and as sensors modifiers. The reviewed sensors and devices were discussed in terms of their suitability for different biosensing applications, in early screening of contamination regarding food analysis, environmental monitoring and in clinical diagnosis.

Recent Advances in the Development of Drug Delivery Applications of Magnetic Nanomaterials.

With the predicted rise in the incidence of cancer, there is an ever-growing need for new cancer treatment strategies. Recently, magnetic nanoparticles have stood out as promising nanostructures for imaging and drug delivery systems as they possess unique properties. Moreover, magnetic nanomaterials functionalized with other compounds can lead to multicomponent nanoparticles with innovative structures and synergetic performance. The incorporation of chemotherapeutic drugs or RNA in magnetic drug delivery systems represents a promising alternative that can increase efficiency and reduce the side effects of anticancer therapy. This review presents a critical overview of the recent literature concerning the advancements in the field of magnetic nanoparticles used in drug delivery, with a focus on their classification, characteristics, synthesis and functionalization methods, limitations, and examples of magnetic drug delivery systems incorporating chemotherapeutics or RNA.

Electrochemical Rapid Detection of Methamphetamine from Confiscated Samples Using a Graphene-Based Printed Platform.

Methamphetamine (MAP) is a highly addictive and illegal stimulant drug that has a significant impact on the central nervous system. Its detection in biological and street samples is crucial for various organizations involved in forensic medicine, anti-drug efforts, and clinical diagnosis. In recent years, nanotechnology and nanomaterials have played a significant role in the development of analytical sensors for MAP detection. In this study, a fast, simple, and cost-effective electrochemical sensor is presented that is used for the sensitive detection of MAP in confiscated street samples with a complex matrix. The optimized screen-printed sensor based on a carbon working electrode modified with graphene demonstrated an excellent limit of detection, good sensitivity, and a wide dynamic range (1-500 µM) for the target illicit drug both for standard solutions and real samples (seized samples, tap water, and wastewater samples). It can detect MAP at concentrations as low as 300 nM in real samples. This limit of detection is suitable for the rapid preliminary screening of suspicious samples in customs, ports, airports, and on the street. Furthermore, the sensor exhibits a good recovery rate, indicating its reliability and repeatability. This quality is crucial for ensuring consistent and accurate results during screening processes.

Special Issue "Women in Science"-The First Edition.

This Special Issue entitled "Women in Biosensors" has been launched to celebrate and highlight the achievements of women in the biosensors research area, presenting biosensor-related work performed in groups leaded by women scientists [...].

Investigating the electrochemical profile of methamphetamine to enable fast on-site detection in forensic analysis.

Methamphetamine (MA) is a synthetic psychoactive drug which is consumed both licitly and illicitly. In some countries it is prescribed for attention-deficit and hyperactivity disorder, and short-term treatment of obesity. More often though, it is abused for its psychostimulant properties. Unfortunately, the spread and abuse of this synthetic drug have increased globally, being reported as the most widely consumed synthetic psychoactive drug in the world in 2019. Attempting to overcome the shortcomings of the currently used on-site methods for MA detection in suspected cargos, the present study explores the potential of electrochemical identification of MA by means of square wave voltammetry on disposable graphite screen-printed electrodes. Hence, the analytical characterization of the method was evaluated under optimal conditions exhibiting a linear range between 50 µM and 2.5 mM MA, a LOD of 16.7 µM, a LOQ of 50.0 µM and a sensitivity of 5.3 µA mM-1. Interestingly, two zones in the potential window were identified for the detection of MA, depending on its concentration in solution. Furthermore, the oxidative pathway of MA was elucidated employing liquid chromatography - mass spectrometry to understand the change in the electrochemical profile. Thereafter, the selectivity of the method towards MA in mixtures with other drugs of abuse as well as common adulterants/cutting agents was evaluated. Finally, the described method was employed for the analysis of MA in confiscated samples and compared with forensic methods, displaying its potential as a fast and easy-to-use method for on-site analysis.

Ara H1 peanut allergen detection using a labelled electrochemical aptasensor based on GO-COOH@bimetallic composite platform.

Allergies are defined as a hypersensitivity reaction, immunologically mediated, as a result to an external stimulus. Peanuts induced allergies are considered one of the most severe, life-threatening food sensitivities since they trigger the highest frequency of severe and fatal reactions, even in trace amounts. Therefore, it is imperative to develop fast, accurate and easy-to-use analytical methods to determine Ara h1, is a seed storage protein from Arachis hypogea and the main peanut derived allergen. In this work, two strategies were applied to develop an electrochemical aptasensor based on GO-COOH and metallic nanoparticles immobilised on screen-printed carbon electrodes (SPCEs). The analytical performances of the aptasensor showed a linear range of 5-150 nM, and a limit of detection of 1.66 nM. The method was applied in peanut-free food samples with very good recoveries proving to be a promising tool for peanut allergy prevention.

Point-of-care electrochemical testing of biomarkers involved in inflammatory and inflammatory-associated medical conditions.

Recent years have shown that the diagnosis and monitoring of biomarkers involved in inflammatory-associated medical conditions such as cancer, neurological disorders, viral infections, or daily physical activities offer real benefits in increasing the quality of medical care and patient life quality. In this context, the use of integrated and portable platforms as point-of-care testing devices for biomedical analysis to enable early disease diagnosis and monitoring, which can be successfully used even at the patient's bed, is an emergency nowadays. The development of low-cost, miniaturized, and portable, user-friendly devices that provide an answer in a timely manner, such as electrochemical sensors, is relevant for the elaboration of point-of-care testing devices. This review focuses on the recent progress in bioanalysis of both specific biomarkers and inflammatory-associated biomarkers present in several diseases like neoplasia, severe neurological disorders, viral infections, and usual physical activity and provides an overview of the state of the art over the most recent electrochemical (bio)sensors for the detection of inflammation-related biomarkers. Future perspectives of point-of-care testing to improve healthcare management are also discussed.

Recent Progress of Electrochemical Aptasensors toward AFB1 Detection (2018-2023).

Food contaminants represent possible threats to humans and animals as severe food safety hazards. Prolonged exposure to contaminated food often leads to chronic diseases such as cancer, kidney or liver failure, immunosuppression, or genotoxicity. Aflatoxins are naturally produced by strains of the fungi species Aspergillus, which is one of the most critical and poisonous food contaminants worldwide. Given the high percentage of contaminated food products, traditional detection methods often prove inadequate. Thus, it becomes imperative to develop fast, accurate, and easy-to-use analytical methods to enable safe food products and good practices policies. Focusing on the recent progress (2018-2023) of electrochemical aptasensors for aflatoxin B1 (AFB1) detection in food and beverage samples, without pretending to be exhaustive, we present an overview of the most important label-free and labeled sensing strategies. Simultaneous and competitive aptamer-based strategies are also discussed. The aptasensors are summarized in tabular format according to the detection mode. Sample treatments performed prior analysis are discussed. Emphasis was placed on the nanomaterials used in the aptasensors' design for aptamer-tailored immobilization and/or signal amplification. The advantages and limitations of AFB1 electrochemical aptasensors for field detection are presented.

Characterization and In Vitro Biocompatibility of Two New Bioglasses for Application in Dental Medicine-A Preliminary Study.

Bioactive glasses (BGs), also known as bioglasses, are very attractive and versatile materials that are increasingly being used in dentistry. For this study, two new bioglasses-one with boron (BG1) and another with boron and vanadium (BG2)-were synthesized, characterized, and tested on human dysplastic keratinocytes. The in vitro biological properties were evaluated through pH and zeta potential measurement, weight loss, Ca2+ ions released after immersion in phosphate-buffered saline (PBS), and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS) analysis. Furthermore, biocompatibility was evaluated through quantification of lactate dehydrogenase activity, oxidative stress, transcription factors, and DNA lesions. The results indicate that both BGs presented the same behavior in simulated fluids, characterized by high degradation, fast release of calcium and boron in the environment (especially from BG1), and increased pH and zeta potential. Both BGs reacted with the fluid, particularly BG2, with irregular deposits covering the glass surface. In vitro studies demonstrated that normal doses of the BGs were not cytotoxic to DOK, while high doses reduced cell viability. Both BGs induced oxidative stress and cell membrane damage and enhanced NFkB activation, especially BG1. The BGs down-regulated the expression of NFkB and diminished the DNA damage, suggesting the protective effects of the BGs on cell death and efficacy of DNA repair mechanisms.

The Use of the QbD Approach to Optimize the Co-Loading of Simvastatin and Doxorubicin in Liposomes for a Synergistic Anticancer Effect.

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.e., phospholipid, SIM and DOX concentration, which were assessed in an optimization experimental design with the purpose of designing an optimal formulation. The optimal formulation, meeting the established quality profile, was additionally characterized in terms of the release profile and antiproliferative effects. During dissolution studies, a novel chronoamperometric method was used for the simultaneous quantification of SIM and DOX. The obtained data confirmed the similarity of this method with a validated HPLC method. The anticancer potential of the optimal formulation was tested against two human cancerous cell lines, namely T47D-KBluc human mammary ductal carcinoma cell line and A549 human pulmonary cancer cell line. The results highlighted that the antiproliferative effect of the optimal formulation is concentration dependent and favors a synergistic effect of the two drugs.

Proof of Concept for the Detection with Custom Printed Electrodes of Enterobactin as a Marker of Escherichia coli.

The rapid and decentralized detection of bacteria from biomedical, environmental, and food samples has the capacity to improve the conventional protocols and to change a predictable outcome. Identifying new markers and analysis methods represents an attractive strategy for the indirect but simpler and safer detection of pathogens that could replace existing methods. Enterobactin (Ent), a siderophore produced by Escherichia coli or other Gram-negative bacteria, was studied on different electrode materials to reveal its electrochemical fingerprint-very useful information towards the detection of the bacteria based on this analyte. The molecule was successfully identified in culture media samples and a future goal is the development of a rapid antibiogram. The presence of Ent was also assessed in wastewater and treated water samples collected from the municipal sewage treatment plant, groundwater, and tap water. Moreover, a custom configuration printed on a medical glove was employed to detect the target in the presence of another bacterial marker, namely pyocyanin (PyoC), that being a metabolite specific of another pathogen bacterium, namely Pseudomonas aeruginosa. Such new mobile and wearable platforms offer considerable promise for rapid low-cost on-site screening of bacterial contamination.

Highly Sensitive Detection of PQS Quorum Sensing in Pseudomonas Aeruginosa Using Screen-Printed Electrodes Modified with Nanomaterials.

The rapid diagnosis of Pseudomonas aeruginosa infection is very important because this bacterium is one of the main sources of healthcare-associated infections. Pseudomonas quinolone signal (PQS) is a specific molecule for quorum sensing (QS) in P. aeruginosa, a form of cell-to-cell bacterial communication and its levels can allow the determination of the bacterial population. In this study, the development of the first electrochemical detection of PQS using screen-printed electrodes modified with carbon nanotubes (CNT-SPE) is reported. The electrochemical fingerprint of PQS was determined using different electrode materials and screen-printed electrodes modified with different nanomaterials. The optimization of the method in terms of electrolyte, pH, and electrochemical technique was achieved. The quantification of PQS was performed using one of the anodic peaks in the electrochemical fingerprint of the PQS on the CNT-SPE. The sensor exhibited a linear range from 0.1 to 15 µM, with a limit of detection of 50 nM. The sensor allowed the selective detection of PQS, with low interference from other QS molecules. The sensor was successfully applied to analysis of real samples (spiked urine and human serum samples, spiked microbiological growth media, and microbiological cultures).

Label-Free Electrochemical Aptasensor for the Detection of the 3-O-C12-HSL Quorum-Sensing Molecule in Pseudomonas aeruginosa.

Pseudomonas aeruginosa, an opportunistic Gram-negative bacterium, is one of the main sources of infections in healthcare environments, making its detection very important. N-3-oxo-dodecanoyl L-homoserine lactone (3-O-C12-HSL) is a characteristic molecule of quorum sensing-a form of cell-to-cell communication between bacteria-in P. aeruginosa. Its detection can allow the determination of the bacterial population. In this study, the development of the first electrochemical aptasensor for the detection of 3-O-C12-HSL is reported. A carbon-based screen-printed electrode modified with gold nanoparticles proved to be the best platform for the aptasensor. Each step in the fabrication of the aptasensor (i.e., gold nanoparticles' deposition, aptamer immobilization, incubation with the analyte) was optimized and characterized using cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy. Different redox probes in solution were evaluated, the best results being obtained in the presence of [Fe(CN)6]4-/[Fe(CN)6]3-. The binding affinity of 106.7 nM for the immobilized thiol-terminated aptamer was determined using surface plasmon resonance. The quantification of 3-O-C12-HSL was performed by using the electrochemical signal of the redox probe before and after incubation with the analyte. The aptasensor exhibited a logarithmic range from 0.5 to 30 µM, with a limit of detection of 145 ng mL-1 (0.5 µM). The aptasensor was successfully applied for the analysis of real samples (e.g., spiked urine samples, spiked microbiological growth media, and microbiological cultures).