MeNPs-PEDOT Composite-Based Detection Platforms for Epinephrine and Quercetin.

The development of low-cost, sensitive, and simple analytical tools for biomolecule detection in health status monitoring is nowadays a growing research topic. Sensing platforms integrating nanocomposite materials as recognition elements in the monitoring of various biomolecules and biomarkers are addressing this challenging objective. Herein, we have developed electrochemical sensing platforms by means of a novel fabrication procedure for biomolecule detection. The platforms are based on commercially available low-cost conductive substrates like glassy carbon and/or screen-printed carbon electrodes selectively functionalized with nanocomposite materials composed of Ag and Au metallic nanoparticles and an organic polymer, poly(3,4-ethylenedioxythiophene). The novel fabrication method made use of alternating currents with controlled amplitude and frequency. The frequency of the applied alternating current was 100 mHz for the polymer deposition, while a frequency value of 50 mHz was used for the in situ electrodeposition of Ag and Au nanoparticles. The selected frequency values ensured the successful preparation of the composite materials. The use of readily available composite materials is intended to produce cost-effective analytical tools. The judicious modification of the organic conductive matrix by various metallic nanoparticles, such as Ag and Au, extends the potential applications of the sensing platform toward a range of biomolecules like quercetin and epinephrine, chosen as benchmark analytes for proof-of-concept antioxidant and neurotransmitter detection. The sensing platforms were tested successfully for quercetin and epinephrine determination on synthetic and real samples. Wide linear response ranges and low limit-of-detection values were obtained for epinephrine and quercetin detection.

3D printable and biocompatible PEDOT:PSS-ionic liquid colloids with high conductivity for rapid on-demand fabrication of 3D bioelectronics.

3D printing has been widely used for on-demand prototyping of complex three-dimensional structures. In biomedical applications, PEDOT:PSS has emerged as a promising material in versatile bioelectronics due to its tissue-like mechanical properties and suitable electrical properties. However, previously developed PEDOT:PSS inks have not been able to fully utilize the advantages of commercial 3D printing due to its long post treatment times, difficulty in high aspect ratio printing, and low conductivity. We propose a one-shot strategy for the fabrication of PEDOT:PSS ink that is able to simultaneously achieve on-demand biocompatibility (no post treatment), structural integrity during 3D printing for tall three-dimensional structures, and high conductivity for rapid-prototyping. By using ionic liquid-facilitated PEDOT:PSS colloidal stacking induced by a centrifugal protocol, a viscoplastic PEDOT:PSS-ionic liquid colloidal (PILC) ink was developed. PILC inks exhibit high-aspect ratio vertical stacking, omnidirectional printability for generating suspended architectures, high conductivity (~286 S/cm), and high-resolution printing (~50 µm). We demonstrate the on-demand and versatile applicability of PILC inks through the fabrication of 3D circuit boards, on-skin physiological signal monitoring e-tattoos, and implantable bioelectronics (opto-electrocorticography recording, low voltage sciatic nerve stimulation and recording from deeper brain layers via 3D vertical spike arrays).

Detection of Crude Oil in Subsea Environments Using Organic Electrochemical Transistors.

Current methods for detecting pipeline oil leaks depend primarily on optical detection, which can be slow and have deployment limitations. An alternative non-optical approach for earlier and faster detection of oil leaks would enable a rapid response and reduce the environmental impact of oil leaks. Here, we demonstrate that organic electrochemical transistors (OECTs) can be used as non-optical sensors for crude oil detection in subsea environments. OECTs are thin film electronic devices that can be used for sensing in a variety of environments, but they have not yet been tested for crude oil detection in subsea environments. We fabricated OECTs with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) as the channel and showed that coating the channel with a polystyrene film results in an OECT with a large and measurable response to oil. Oil that comes in contact with the device will adsorb onto the polystyrene film and increases the impedance at the electrolyte interface. We performed electrochemical impedance spectroscopy measurements to quantify the impedance across the device and found an optimal thickness for the polystyrene coating for the detection of oil. Under optimal device characteristics, as little as 10 µg of oil adsorbed on the channel surface produced a statistically significant change in the source-drain current. The OECTs were operable in seawater for the detection of oil, and we demonstrated that the devices can be transferred to flexible substrates which can be easily implemented in vehicles, pipelines, or other surfaces. This work demonstrates a low-cost device for oil detection in subsea environments and provides a new application of OECT sensors for sensing.

Development and validation of the RP-HPLC method for quantification of tavaborole.

The stability-indicating approach for tavaborole quantification was developed and validated to establish a precise, linear, accurate, and robust HPLC method. The development section includes optimizing the detection wavelength, the mobile phase ratio, and the type of column used to achieve the best possible separation and sensitivity for analysis. The chromatographic conditions were established, considering peak symmetry, resolution, and retention time. The mobile phase composition, comprising a buffer: acetonitrile (75 : 25, %v/v), with an injection volume of 15 µL, showed suitable elution and recovery at 265 nm. A constant column oven temperature of 35 °C and a 1 mL min-1 flow rate were maintained. The pH of the buffer was changed to 3.0 by using orthophosphoric acid. Linearity was observed from 5 to 1000 ppm (r2 = 1.00000). The capacity (retention) factor (k) of 3.43 was observed, indicating significant interaction and good separation. Forced degradation (FD) or stress tests were performed for chemical and physical photolytic stress conditions, and the results observed were within the specified limits. The stability in the analytical solution was observed for up to 35 hours at 5 °C, confirming the stability of the solution. Validation of the developed HPLC method confirmed the system's suitability, precision, linearity, accuracy, FD, robustness, and results. All validation criteria for the technique were within acceptable limits.

Nanoemulsion based lipid nanoparticles for effective demethylcantharidin delivery to cure liver cancer.

Demethylcantharidin (DEM) is a widely used antitumor drug; however, its poor tumor targeting and serious organotoxicity limit its application. The aim of this study was to develop a new drug delivery system for efficient delivery of DEM. Nanoemulsion based lipid nanoparticles containing demethylcantharidin (DNLNs) were prepared by loading nanoemulsions into lipid nanoparticles. The cells proliferation, apoptosis, cycle, and uptake were investigated by Cell counting kit-8 (CCK-8), flow cytometry, and in situ fluorescence assays, respectively. Then, we established the H22 tumor-bearing mouse model to evaluate the antitumor efficacy of DNLNs and further studied its organ toxicity and distribution. DNLNs significantly inhibited the proliferation and promoted apoptosis of H22 cells, and H22 cells could take up more DNLNs. Compared with DEM, DNLNs had certain tumor-targeting properties, and the tumor inhibition rate increased by 23.24%. Moreover, DNLNs can increase white blood cell count and reduce organ toxicity. This study paves the way for nanoemulsion-based lipid nanoparticle (NLNs)-efficient DEM delivery to treat liver cancer.

Eco-Friendly Textile-Based Wearable Humidity Sensor with Multinode Wireless Connectivity for Healthcare Applications.

Textile-based wearable humidity sensors are of great interest for human healthcare monitoring as they can provide critical human-physiology information. The demand for wearable and sustainable sensing technology has significantly promoted the development of eco-friendly sensing solutions for potential real-world applications. Herein, a biodegradable cotton (textile)-based wearable humidity sensor has been developed using fabsil-treated cotton fabric coated with a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) sensing layer. The structural, chemical composition, hygroscopicity, and morphological properties are examined using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), contact angle measurement, and scanning electron microscopy (SEM) analysis. The developed sensor exhibited a nearly linear response (Adj. R-square value observed as 0.95035) over a broad relative humidity (RH) range from 25 to 91.5%RH displaying high sensitivity (26.1%/%RH). The sensor shows excellent reproducibility (on replica sensors with a margin of error ±1.98%) and appreciable stability/aging with time (>4.5 months), high flexibility (studied at bending angles 30°, 70°, 120°, and 150°), substantial response/recovery durations (suitable for multiple applications), and highly repeatable (multicyclic analysis) sensing performance. The prospective relevance of the developed humidity sensor toward healthcare applications is demonstrated via breathing rate monitoring (via a sensor attached to a face mask), distinguishing different breathing patterns (normal, deep, and fast), skin moisture monitoring, and neonatal care (diaper wetting). The multinode wireless connectivity is demonstrated using a Raspberry Pi Pico-based system for demonstrating the potential applicability of the developed sensor as a real-time humidity monitoring system for the healthcare sector. Further, the biodegradability analysis of the used textile is evaluated using the soil burial degradation test. The work suggests the potential applicability of the developed flexible and eco-friendly humidity sensor in wearable healthcare devices and other humidity sensing applications.

Evaluation of a Voltametric E-Tongue Combined with Data Preprocessing for Fast and Effective Machine Learning-Based Classification of Tomato Purées by Cultivar.

The potential of a voltametric E-tongue coupled with a custom data pre-processing stage to improve the performance of machine learning techniques for rapid discrimination of tomato purées between cultivars of different economic value has been investigated. To this aim, a sensor array with screen-printed carbon electrodes modified with gold nanoparticles (GNP), copper nanoparticles (CNP) and bulk gold subsequently modified with poly(3,4-ethylenedioxythiophene) (PEDOT), was developed to acquire data to be transformed by a custom pre-processing pipeline and then processed by a set of commonly used classifiers. The GNP and CNP-modified electrodes, selected based on their sensitivity to soluble monosaccharides, demonstrated good ability in discriminating samples of different cultivars. Among the different data analysis methods tested, Linear Discriminant Analysis (LDA) proved to be particularly suitable, obtaining an average F1 score of 99.26%. The pre-processing stage was beneficial in reducing the number of input features, decreasing the computational cost, i.e., the number of computing operations to be performed, of the entire method and aiding future cost-efficient hardware implementation. These findings proved that coupling the multi-sensing platform featuring properly modified sensors with the custom pre-processing method developed and LDA provided an optimal tradeoff between analytical problem solving and reliable chemical information, as well as accuracy and computational complexity. These results can be preliminary to the design of hardware solutions that could be embedded into low-cost portable devices.

A PEDOT: PSS/GO fiber microelectrode fabricated by microfluidic spinning for dopamine detection in human serum and PC12 cells.

Rapid and accurate in situ determination of dopamine is of great significance in the study of neurological diseases. In this work, poly (3,4-ethylenedioxythiophene): poly (styrenesulfonic acid) (PEDOT: PSS)/graphene oxide (GO) fibers were fabricated by an effective method based on microfluidic wet spinning technology. The composite microfibers with stratified and dense arrangement were continuously prepared by injecting PEDOT: PSS and GO dispersion solutions into a microfluidic chip. PEDOT: PSS/GO fiber microelectrodes with high electrochemical activity and enhanced electrochemical oxidation activity of dopamine were constructed by controlling the structure composition of the microfibers with varying flow rate. The fabricated fiber microelectrode had a low detection limit (4.56 nM) and wide detection range (0.01-8.0 µM) for dopamine detection with excellent stability, repeatability, and reproducibility. In addition, the PEDOT: PSS/GO fiber microelectrode prepared was successfully used for the detection of dopamine in human serum and PC12 cells. The strategy for the fabrication of multi-component fiber microelectrodes is a new and effective approach for monitoring the intercellular neurotransmitter dopamine and has high potential as an implantable neural microelectrode.

Material modification of electrodes in microbial electrochemical system to enhance electrons utilization on the electrode and its impact on microorganisms.

Previous research has established a MES embedding a microbial electrode to facilitate the degradation of antibiotics in water. We modified microbial electrodes in the MES with PEDOT and rGO to enhance electron utilization on electrodes and to further promote antibiotic degradation. Density functional theory calculations on the SMX molecule indicated that the C4-S8 and S8-N27 bonds are the most susceptible to electron attack. The introduction of various functional groups and multivalent elements enhanced the electrodes' capacitance and electron mediation capabilities. This led to enhance both electron utilization on the electrodes and the removal efficiency of SMX. After 120 h, the degradation efficiency of SMX by PEDOT and rGO-modified electrodes increased by 45.47 % and 25.19 %, respectively, compared to unmodified electrodes. The relative abundance of sulfate-reducing and denitrifying bacteria significantly increased in PEDOT and rGO-modified electrodes, while the abundance of nitrifying bacteria and potential antibiotic resistance gene host microbes significantly decreased. The impact of PEDOT modification positively influenced microbial Cellular Processes, including cell growth, death, and motility. This study provides insights into the mechanisms of direct electron involvement in antibiotic degradation steps in microbial electrochemistry, and provides a possible path for improved strategies in antibiotic degradation and sustainable environmental remediation.

Marine Cytotoxin Santacruzamate A Derivatives as Potent HDAC1-3 Inhibitors and Their Synergistic Anti-Leukemia Effects with Venetoclax.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.

Flexible Wearable Electrochemical Sensors Based on AuNR/PEDOT:PSS for Simultaneous Monitoring of Levodopa and Uric Acid in Sweat.

As a facile substitute for the invasive technique of blood testing, wearable electrochemical sensors exhibit high potential for the noninvasive and real-time monitoring of biomarkers in human sweat. However, owing to enzyme specificity, the simultaneous detection of multiple biomarkers by enzymatic analysis is challenging. Moreover, sweat accumulation under sensors causes sweat contamination, which hinders real-time biomarker detection from sweat. This study reports the design and fabrication of flexible wearable electrochemical sensors containing a composite comprising Au nanorods (AuNRs) and poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) for the nonenzymatic detection of levodopa (LD) and uric acid (UA) in sweat. Each sensor was integrated with a flexible three-electrode system and a microfluidic patch for sweat sampling. AuNRs immobilized by PEG-doped PEDOT:PSS showed excellent analytical performance for LD and UA at different potentials. Thus, the newly fabricated sensors could detect LD and UA over a broad detection range with high sensitivity and showed a low limit of detection for both species. On-body assessments confirmed the ability of these sensors to simultaneously detect LD and UA in real time. Therefore, this study could open new frontiers in the fabrication of wearable electrochemical sensors for the pharmacokinetic profile tracking of LD and gout management.

Tuning the Emission of Bis-ethylenedioxythiophene-thiophenes upon Aggregation.

The ability of small lipophilic molecules to penetrate the blood-brain barrier through transmembrane diffusion has enabled researchers to explore new diagnostics and therapies for brain disorders. Until now, therapies targeting the brain have mainly relied on biochemical mechanisms, while electrical treatments such as deep brain stimulation often require invasive procedures. An alternative to implanting deep brain stimulation probes could involve administering small molecule precursors intravenously, capable of crossing the blood-brain barrier, and initiating the formation of conductive polymer networks in the brain through in vivo polymerization. This study examines the aggregation behavior of five water-soluble conducting polymer precursors sharing the same conjugate core but differing in side chains, using spectroscopy and various computational chemistry tools. Our findings highlight the significant impact of side chain composition on both aggregation and spectroscopic response.

Electrochemical detection of carbendazim using molecularly imprinted poly(3,4-ethylenedioxythiophene) on Co,N co-doped hollow carbon nanocage@CNTs-modified electrode.

Precisely detecting trace pesticides and their residues in food products is crucial for ensuring food safety. Herein, a high-performance electrochemical sensing platform was developed for the detection of carbendazim (CBZ) using Co,N co-doped hollow carbon nanocage@carbon nanotubes (Co,N-HC@CNTs) obtained from core-shell ZIF-8@ZIF-67 combined with a poly(3,4-ethylenedioxythiophene) (PEDOT) molecularly imprinted polymer (MIP). The Co,N-HC@CNTs exhibited excellent electrocatalytic performance, benefitting from the synergistic effect of CNTs that provide a large specific surface area and excellent electrical conductivity, Co,N co-doped carbon nanocages that offer high electrocatalytic activity and hollow nanocage structures that ensure rapid diffusion kinetics. The conductive PEDOT-MIP provided specific binding sites for CBZ detection and significantly amplified the detection signal. The sensor showed superior selectivity for CBZ with an extremely low detection limit of 1.67 pmol L-1. Moreover, the method was successfully applied to detect CBZ in tomato, orange and apple samples, achieving satisfactory recovery and accuracy, thus demonstrating its practical feasibility.

Printable Poly(3,4-ethylenedioxythiophene)-Based Conductive Patches for Cardiac Tissue Remodeling.

Myocardial cardiopathy is one of the highest disease burdens worldwide. The damaged myocardium has little intrinsic repair ability, and as a result, the distorted muscle loses strength for contraction, producing arrhythmias and fainting, and entails a high risk of sudden death. Permanent implantable conductive hydrogels that can restore contraction strength and conductivity appear to be promising candidates for myocardium functional recovery. In this work, we present a printable cardiac hydrogel that can exert functional effects on networks of cardiac myocytes. The hydrogel matrix was designed from poly(vinyl alcohol) (PVA) dynamically cross-linked with gallic acid (GA) and the conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting patches exhibited excellent electrical conductivity, elasticity, and mechanical and contractile strengths, which are critical parameters for reinforcing weakened cardiac contraction and impulse propagation. Furthermore, the PVA-GA/PEDOT blend is suitable for direct ink writing via a melting extrusion. As a proof of concept, we have proven the efficiency of the patches in propagating the electrical signal in adult mouse cardiomyocytes through in vitro recordings of intracellular Ca2+ transients during cell stimulation. Finally, the patches were implanted in healthy mouse hearts to demonstrate their accommodation and biocompatibility. Magnetic resonance imaging revealed that the implants did not affect the essential functional parameters after 2 weeks, thus showing great potential for treating cardiomyopathies.

Smartphone-enabled flow injection amperometric glucose monitoring based on a screen-printed carbon electrode modified with PEDOT@PB and a GOx@PPtNPs@MWCNTs nanocomposite.

This study presents a modified screen-printed carbon electrode (SPCE) to determine glucose in a custom-built flow injection system. The biosensor was constructed by immobilizing glucose oxidase on porous platinum nanoparticles decorated on multi-walled carbon nanotubes (GOx@PPtNPs@MWCTNs). The fabrication of the biosensor was completed by coating the GOx@PPtNPs@MWCTNs nanocomposite on an SPCE modified with a nanocomposite of poly(3,4-ethylenedioxythiophene) and Prussian blue (GOx@PPtNPs@MWCTNs/PEDOT@PB/SPCE). The fabricated electrode accurately measured hydrogen peroxide (H2O2), the byproduct of the GOx-catalyzed oxidation of glucose, and was then applied as a glucose biosensor. The glucose response was amperometrically determined from the PB-mediated reduction of H2O2 at an applied potential of -0.10 V in a flow injection system. Under optimal conditions, the developed biosensor produced a linear range from 2.50 µM to 1.250 mM, a limit of detection of 2.50 µM, operational stability over 500 sample injections, and good selectivity. The proposed biosensor determined glucose in human plasma samples, achieving recoveries and results that agreed with the hexokinase-spectrophotometric method (P > 0.05). Combining the proposed biosensor with the custom-built sample feed, a portable potentiostat and a smartphone, enabled on-site glucose monitoring.

Discovery of a Covalent Inhibitor That Overcame Resistance to Venetoclax in AML Cells Overexpressing BFL-1.

Clinical and biological studies have shown that overexpression of BFL-1 is one contributing factor to venetoclax resistance. The resistance might be overcome by a potent BFL-1 inhibitor, but such an inhibitor is rare. In this study, we show that 56, featuring an acrylamide moiety, inhibited the BFL-1/BID interaction with a Ki value of 105 nM. More interestingly, 56 formed an irreversible conjugation adduct at the C55 residue of BFL-1. 56 was a selective BFL-1 inhibitor, and its MCL-1 binding affinity was 10-fold weaker, while it did not bind BCL-2 and BCL-xL. Mechanistic studies showed that 56 overcame venetoclax resistance in isogenic AML cell lines MOLM-13-OE and MV4-11-OE, which both overexpressed BFL-1. More importantly, 56 and venetoclax combination promoted stronger apoptosis induction than either single agent. Collectively, our data show that 56 overcame resistance to venetoclax in AML cells overexpressing BFL-1. These attributes make 56 a promising candidate for future optimization.

Computational therapeutic repurposing of tavaborole targeting arginase-1 for venous leg ulcer.

Venous leg ulcers (VLUs) pose a growing healthcare challenge due to aging, obesity, and sedentary lifestyles. Despite various treatments available, addressing the complex nature of VLUs remains difficult. In this context, this study investigates repurposing boronated drugs to inhibit arginase 1 activity for VLU treatment. The molecular docking study conducted by Schrodinger GLIDE targeted the binuclear manganese cluster of arginase 1 enzyme (2PHO). Further, the ligand-protein complex was subjected to molecular dynamic studies at 500 ns in Gromacs-2019.4. Trajectory analysis was performed using the GROMACS simulation package of protein RMSD, RMSF, RG, SASA, and H-Bond. The docking study revealed intriguing results where the tavaborole showed a better docking score (-3.957 Kcal/mol) compared to the substrate L-arginine (-3.379 Kcal/mol) and standard L-norvaline (-3.141 Kcal/mol). Tavaborole interaction with aspartic acid ultimately suggests that the drug molecule binds to the catalytic site of arginase 1, potentially influencing the enzyme's function. The dynamics study revealed the compounds' stability and compactness of the protein throughout the simulation. The RMSD, RMSF, SASA, RG, inter and intra H-bond, PCA, FEL, and MMBSA studies affirmed the ligand-protein and protein complex flexibility, compactness, binding energy, van der waals energy, and solvation dynamics. These results revealed the stability and the interaction of the ligand with the catalytic site of arginase 1 enzyme, triggering the study towards the VLU treatment.

Array-wide uniform PEDOT:PSS electroplating from potentiostatic deposition.

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics.

Dual electro-/pH-responsive nanoparticle/hydrogel system for controlled delivery of anticancer peptide.

An electro-chemo-responsive carrier has been engineered for the controlled release of a highly hydrophilic anticancer peptide, CR(NMe)EKA (Cys-Arg- N-methyl-Glu-Lys-Ala). Remotely controlled on demand release of CR(NMe)EKA, loaded in electro-responsive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles, has been achieved by applying electrical stimuli consisting of constant positive (+0.50 V) or negative voltages (-0.50 V) at pre-defined time intervals. In addition, after loading CR(NMe)EKA/PEDOT nanoparticles into an injectable pH responsive hydrogel formed by phenylboronic acid grafted to chitosan (PBA-CS), the efficiency of the controlled peptide release has increased approximately by a factor of 2.6. The hydration ratio of such hydrogel is significantly lower in acidic environments than in neutral and basic media, which has been attributed to the dissociation of the boronate bonds between polymer chains. Hence, the electro-controlled peptide release from PBA-CS/CR(NMe)EKA/PEDOT hydrogels, in the acidic environment of tumors, combines the effects of the oxidation and reduction of PEDOT chains on the interactions with the peptide and the carrier, with the peptide concentration gradient at the interface between the collapsed hydrogel and the release medium. Furthermore, the peptide released by electro-stimulation preserved its bioactivity assessed by promoting human prostate cancer cells death. Overall, this work is a promising attempt to develop a carrier platform for small hydrophilic anticancer peptides, which delivery rationale is synergistically regulated by the electrical and pH responsiveness of the carrier.

Molecular Memory Micromotors for Fast Snake Venom Toxin Dynamic Detection.

The analysis and detection of snake venom toxins are a matter of great importance in clinical diagnosis for fast treatment and the discovery of new pharmaceutical products. Current detection methods have high associated costs and require the use of sophisticated bioreceptors, which in some cases are difficult to obtain. Herein, we report the synthesis of template-based molecularly imprinted micromotors for dynamic detection of α-bungarotoxin as a model toxin present in the venom of many-banded krait (Bungarus multicinctus). The specific recognition sites are built-in in the micromotors by incubation of the membrane template with the target toxin, followed by a controlled electrodeposition of a poly(3,4-ethylenedioxythiophene)/poly(sodium 4-styrenesulfonate) polymeric layer, a magnetic Ni layer to promote magnetic guidance and facilitate washing steps, and a Pt layer for autonomous propulsion in the presence of hydrogen peroxide. The enhanced fluid mixing and autonomous propulsion increase the likelihood of interactions with the target analyte as compared with static counterparts, retaining the tetramethylrhodamine-labeled α-bungarotoxin on the micromotor surface with extremely fast dynamic sensor response (after just 20 s navigation) in only 3 µL of water, urine, or serum samples. The sensitivity achieved meets the clinically relevant concentration postsnakebite (from 0.1 to 100 µg/mL), illustrating the feasibility of the approach for practical applications. The selectivity of the protocol is very high, as illustrated by the absence of fluorescence in the micromotor surface in the presence of α-cobratoxin as a representative toxin with a size and structure similar to those of α-bungarotoxin. Recoveries higher than 95% are obtained in the analysis of urine- and serum-fortified samples. The new strategy holds considerable promise for fast, inexpensive, and even onsite detection of several toxins using multiple molecularly imprinted micromotors with tailored recognition abilities.