Modified Au:Fe-Ni magnetic micromotors improve drug delivery and diagnosis in MCF-7 cells and spheroids.

Nano/micromotors hold immense potential for revolutionizing drug delivery and detection systems, especially in the realm of cancer diagnosis and treatment, owing to their distinctive features, including precise propulsion, maneuverability, and meticulously designed surface modifications. In this study, we explore the capabilities of modified and magnetically driven micromotors as active drug delivery systems within 2D and 3D cell culture environments and cancer diagnosis. We synthesized gold (Au) and iron-nickel (Fe-Ni) metallic-based magnetic micromotors (Au:Fe-Ni MMs) through electrochemical methods, equipping them with functionalities for controlled doxorubicin (DOX) release and cancer cell recognition. In 2D and spheroids of MCF-7 adenocarcinoma cells, the Au segment of these micromotors was utilized to help DOX loading through poly(sodium-4-styrenesulfonate) (PSS) functionalization, and the attachment of antiHER2 antibodies for specific recognition. This innovative approach enabled controlled drug release within the cancerous microenvironment, coupled with magnetic (Fe-Ni) propulsion for biocompatible drug delivery to MCF-7 cells. Furthermore, antiHER2 immobilized Au:Fe-Ni MMs effectively interacted with receptors, capitalizing on the overexpression of HER2 antigens on MCF-7 cells. Encouraging outcomes were observed, particularly in spheroid models, underscoring the remarkable potential of these multifunctional micromotors for advancing intelligent drug delivery methodologies and diagnostic purposes.

Label-Free Electrochemical Biosensor Platforms for Cancer Diagnosis: Recent Achievements and Challenges.

With its fatal effects, cancer is still one of the most important diseases of today's world. The underlying fact behind this scenario is most probably due to its late diagnosis. That is why the necessity for the detection of different cancer types is obvious. Cancer studies including cancer diagnosis and therapy have been one of the most laborious tasks. Since its early detection significantly affects the following therapy steps, cancer diagnosis is very important. Despite researchers' best efforts, the accurate and rapid diagnosis of cancer is still challenging and difficult to investigate. It is known that electrochemical techniques have been successfully adapted into the cancer diagnosis field. Electrochemical sensor platforms that are brought together with the excellent selectivity of biosensing elements, such as nucleic acids, aptamers or antibodies, have put forth very successful outputs. One of the remarkable achievements of these biomolecule-attached sensors is their lack of need for additional labeling steps, which bring extra burdens such as interference effects or demanding modification protocols. In this review, we aim to outline label-free cancer diagnosis platforms that use electrochemical methods to acquire signals. The classification of the sensing platforms is generally presented according to their recognition element, and the most recent achievements by using these attractive sensing substrates are described in detail. In addition, the current challenges are discussed.

Achievements of Graphene and Its Derivatives Materials on Electrochemical Drug Assays and Drug-DNA Interactions.

Graphene, emerging as a true two-dimensional (2D) material, has attracted increasing attention due to its unique physical and electrochemical properties such as high surface area, excellent conductivity, high mechanical strength, and ease of functionalization and mass production. The entire scientific community recognizes the significance and potential impact of graphene. Electrochemical detection strategies have advantages such as being simple, fast, and low-cost. The use of graphene as an excellent interface for electrode modification provides a promising way to construct more sensitive and stable electrochemical (bio)sensors. The review presents sensors based on graphene and its derivatives for electrochemical drug assays from pharmaceutical dosage forms and biological samples. Future perspectives in this rapidly developing field are also discussed. In addition, the interaction of several important anticancer drug molecules with deoxyribonucleic acid (DNA) that was immobilized onto graphene-modified electrodes has been detailed in terms of dosage regulation and utility purposes.

Chitosan functionalized gold-nickel bimetallic magnetic nanomachines for motion-based deoxyribonucleic acid recognition.

In this present study, the preparation of chitosan functionalized gold­nickel wire nanomachines (nanomotors) (CS@Au-Ni NMs) for motion-based double-stranded deoxyribonucleic acid (dsDNA) recognition and detection was described. Synthesis of the nanomachines was accomplished by Ni layer formation using direct current (DC) magnetron sputtering over electrochemically deposited Au wires. Subsequently, biopolymer chitosan was dispersed onto this bimetallic layer by drop casting which could provide a novel and functional surface for leading bio-applications. CS@Au-Ni NMs were characterized via scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and zeta potential analysis methods for the elucidation of structural morphology, elemental composition and electrophoretic mobility. On account of presenting the application of these magnetic nanomachines, they were interacted with different concentrations of dsDNA and the changes in their velocities were investigated. The speed CS@Au-Ni NMs were measured as 19 µm/s under 22 mT magnetic field. These magnetically guided nanomachines demonstrated a practical and good sensing ability by recognizing dsDNA between 0.01 mg/L and 10 mg/L. Electrochemical characterization was also performed to identify the surface characteristics. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) experiments presented the interaction of the NMs with dsDNA by indicating the convenient recognition.

Current status of micro/nanomotors in drug delivery.

Synthetic micro/nanomotors (MNMs) are novel, self-propelled nano or microscale devices that are widely used in drug transport, cell stimulation and isolation, bio-imaging, diagnostic and monitoring, sensing, photocatalysis and environmental remediation. Various preparation methods and propulsion mechanisms make MNMs "tailormade" nanosystems for the intended purpose or use. As the one of the newest members of nano carriers, MNMs open a new perspective especially for rapid drug transport and gene delivery. Although there exists limited number of in-vivo studies for drug delivery purposes, existence of in-vitro supportive data strongly encourages researchers to move on in this field and benefit from the manoeuvre capability of these novel systems. In this article, we reviewed the preparation and propulsion mechanisms of nanomotors in various fields with special attention to drug delivery systems.

RF plasma-enhanced conducting Polymer/W5O14 based self-propelled micromotors for miRNA detection.

Functionalized micro/nanomotors having immobilized biological molecules provide excellent and powerful tools for the detection of target molecules. Based on surface modifications and mobilities of micromotors, we report herein a new experimental design of high-speed, self-propelled and plasma modified micromotors for biomedical applications. Within this scope, in the first step, poly (3,4-ethylenedioxythiophene) (PEDOT) was in-situ synthesized onto W5O14 (tungsten trioxide) wires by using radio frequency (RF) rotating plasma reactor. Then, W5O14/PEDOT-Platinum (Pt) hybrid micromotors were fabricated by using magnetron sputtering technique. The detection of miRNA-21 was performed using both single-stranded DNA (ssDNA) (probe DNA) immobilized W5O14-Pt and W5O14/PEDOT-Pt micromotors. The fluorescence signals were determined after hybridization of probe DNA immobilized these novel W5O14-Pt and W5O14/PEDOT-Pt micromotors with different molar concentrations of the synthetic target (6-carboxyfluorescein dye (FAM)-labeled miRNA-21). The changes in the micromotor speeds after the hybridization process were also evaluated. W5O14/PEDOT-Pt micromotors presented better sensor properties compared to the W5O14-Pt micromotors. A good linearity for miRNA-21 concentration between 0.1 nM and 100 nM was obtained for these micromotors based on their fluorescence intensities. The detection limit was found as 0.028 nM for W5O14/PEDOT-Pt micromotors (n = 3). Thus, sensor and motor characteristics of the W5O14-Pt micromotors were improved by RF plasma enhanced PEDOT coatings. The new catalytic W5O14 based micromotors demonstrated here had great potential for the development of sensitive and simple sensing platforms for detection of miRNA-21.

Electroactive polyglycine coatings for nanobiosensing applications: Label-free DNA hybridization, DNA-Antitumor agent interaction and antitumor agent determination.

Bioinspired materials have attracted great attention due to their great functionality, bioactivity and biocompability. In particular, electroactive polyamino acid surfaces endow preparation of robust coatings for various applications. In this research article, preparation of carbon nanotubes doped polyglycine coated electrodes and their applications in the biomedical field such as DNA hybridization, DNA-antitumor agent interaction and antitumor agent determination were described. This biosensing platform was created using a simple, reproducible and fast in situ and one-pot electropolymerization procedure onto graphite surfaces by cyclic voltammetry. The coated electrodes were characterized with cyclic voltammetry and electrochemical impedance spectroscopy (EIS). After the characterization studies, bioapplications of the proposed electrode were demonstrated. The new electrode led to significant improvement for the investigation of the electrochemical behavior of double-stranded DNA (dsDNA). 6-fold and 5-fold improvements were obtained for oxidation of the electroactive DNA bases, guanine (G) and adenine (A), respectively over the bare electrode. For these steps, each electrode was characterized with scanning electron microscopy (SEM) and energy dispersive X-ray (EDX). Then, DNA hybridization studies were performed in the light of these results. The proposed electrode allowed the quantification of specific target DNA down to 11.2 fM in serum samples (n = 3). In addition, it constituted a sensitive biosensing platform for electrochemical monitoring of the interaction between dsDNA and a commonly used antitumor agent, Mitomycin C. Mitomycin C determination was also carried out using the inhibition effect occurred at the guanine oxidation signal. The detection limit of this antitumor agent was found as 1.78 mg L-1 in untreated serum samples (n = 3).

Poly-L-lysine Coated Surfaces for Ultrasensitive Nucleic Acid Detection.

Poly-L-lysine is one of the biocompatible polymers having amino and carboxyl groups in its structure. This attractive feature of poly-L-lysine makes it very convenient for bioactive molecule attachment. This study details the preparation of poly-L-lysine-based pencil graphite electrodes (PLL/PGEs) and use of the coated electrodes for direct ultrasensitive DNA hybridization detection. In the first part of this study, poly-L-lysine coated electrodes were prepared using L-lysine as the monomer by cyclic voltammetry (CV) with different cyclic scans. The effect of these cyclic scans during the electropolymerization was investigated. Coated electrodes were characterized by cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). Then, one-pot preparation of poly-L-lysine composites with graphene (GN) and multi-walled carbon nanotubes (MWCNTs) onto the pencil graphite electrodes were achieved. Electrochemical responses of these 3 electrodes were compared. After all, electrochemical DNA hybridization was performed using the poly-L-lysine-based electrodes prepared at optimum polymerization condition. The PLL/PGE coated electrode presented a good linear response in the target concentration range of 1.0×10-13 to 1.0×10-6 with a detection limit of 2.25×10-14 using differential pulse voltammetry as the detection method. We believe that poly-L-lysine-based surfaces will be useful for further clinical applications.

Electrochemical bacterial detection using poly(3-aminophenylboronic acid)-based imprinted polymer.

Biosensors can deliver the rapid bacterial detection that is needed in many fields including food safety, clinical diagnostics, biosafety and biosecurity. Whole-cell imprinted polymers have the potential to be applied as recognition elements in biosensors for selective bacterial detection. In this paper, we report on the use of 3-aminophenylboronic acid (3-APBA) for the electrochemical fabrication of a cell-imprinted polymer (CIP). The use of a monomer bearing a boronic acid group, with its ability to specifically interact with cis-diol, allowed the formation of a polymeric network presenting both morphological and chemical recognition abilities. A particularly beneficial feature of the proposed approach is the reversibility of the cis-diol-boronic group complex, which facilitates easy release of the captured bacterial cells and subsequent regeneration of the CIP. Staphylococcus epidermidis was used as the model target bacteria for the CIP and electrochemical impedance spectroscopy (EIS) was explored for the label-free detection of the target bacteria. The modified electrodes showed a linear response over the range of 103-107cfu/mL. A selectivity study also showed that the CIP could discriminate its target from non-target bacteria having similar shape. The CIPs had high affinity and specificity for bacterial detection and provided a switchable interface for easy removal of bacterial cell.

Biosensing applications of titanium dioxide coated graphene modified disposable electrodes.

In the present work, preparation of titanium dioxide coated graphene (TiO2/graphene) and the use of this nanocomposite modified electrode for electrochemical biosensing applications were detailed. The nanocomposite was prepared with radio frequency (rf) rotating plasma method which serves homogeneous distribution of TiO2 onto graphene. TiO2/graphene was characterized with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) analysis. Then, this nanocomposite was dissolved in phosphate buffer solution (pH 7.4) and modified onto disposable pencil graphite electrode (PGE) by dip coating for the investigation of the biosensing properties of the prepared electrode. TiO2/graphene modified PGE was characterized with SEM, EDS and cyclic voltammetry (CV). The sensor properties of the obtained surface were examined for DNA and DNA-drug interaction. The detection limit was calculated as 1.25mgL(-1) (n=3) for double-stranded DNA (dsDNA). RSD% was calculated as 2.4% for three successive determinations at 5mgL(-1) dsDNA concentration. Enhanced results were obtained compared to the ones obtained with graphene and unmodified (bare) electrodes.

Polymer/carbon nanotubes coated graphite surfaces for highly sensitive nitrite detection.

This study describes the preparation of poly(vinylferrocenium)/multi-walled carbon nanotubes (PVF(+)/MWCNTs) coated electrode and its use for sensitive electrochemical nitrite detection. PVF(+)/MWCNTs composite coated disposable pencil graphite electrode (PVF(+)/MWCNTs/PGE) was prepared by electropolymerization of poly(vinylferrocene) (PVF) in the presence of MWCNTs with one-step electropolymerization. Characterization of PVF(+)/MWCNTs/PGE was carried out with scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Then electrochemical detection of nitrite was performed using differential pulse voltammetry (DPV). Nanocomposite coated electrode showed high sensitivity to nitrite with a detection limit of 0.1 µM. The electrode platform was successfully applied to a commercial mineral water sample.

Poly(3,4-ethylenedioxythiophene) coated chitosan modified disposable electrodes for DNA and DNA-drug interaction sensing.

The need for sensitive, selective, rapid and low-cost detection systems for DNA and DNA-drug interactions are in crucial demand for diagnostics and real-world applications. This work details the preparation of poly(3,4-ethylenedioxythiophene) (PEDOT) coated chitosan (CHIT) and the use of PEDOT coated CHIT modified disposable pencil graphite electrodes (PGEs) for DNA and DNA-anticancer drug interaction sensing. PEDOT coated CHIT (PEDOT/CHIT) was prepared with rotating plasma polymerization using radio frequency (RF: 13.56 MHz) power generator. Then, modification of PEDOT/CHIT onto PGE was performed. The use of the prepared electrode was carried out using differential pulse voltammetry (DPV). Cyclic voltammetry (CV) and scanning electron microscopy (SEM) were used to characterize the PEDOT/CHIT/PGE. The performance of the electrode was compared with CHIT/PGE and unmodified PGE. The electrode exhibited high sensitivity for the investigation of DNA sensing and DNA-anticancer drug interaction. Such disposable sensing platform hold considerable promise for diverse bioapplications.

Leptin-to-adiponectin ratio in obese adolescents with nonalcoholic fatty liver disease.

The leptin-to-adiponectin (L/A) ratio has been used to show insulin resistance (IR) in recent years. The aim of this study was to investigate the L/A ratio in obese adolescents and compare this ratio in patients with and without nonalcoholic fatty liver disease (NAFLD) and also with healthy controls. The second aim was to search the possible correlations between the L/A ratio with the markers of IR and inflammation. A total of 47 obese (mean age: 13.1±2.1 years) and 19 healthy children (mean age: 13.8±0.3 years) were included in the study. The presence of fatty liver was identified by ultrasonography. Cases were divided into three groups as NAFLD (+) and NAFLD (-) obese patients and controls. Liver biochemistries, insulin and serum lipids, C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, adiponectin, and leptin were determined. The L/A ratio was calculated. IR was estimated according to the homeostasis model assessment of insulin resistance (HOMA-IR). The L/A ratio was significantly higher in NAFLD (+) patients than in the other two groups, and in NAFLD (-) patients than the healthy peers. Moreover, L/A ratio correlated more strongly with weight for height (r: 0.528, p<0.0001), alanine aminotransferase (ALT) (r: 0.499, p<0.0001), triglyceride (r: 0.591, p<0.0001), and HOMA-IR (r: 0.574, p<0.0001) than did either leptin and adiponectin alone. This study shows that the L/A ratio is a noninvasive predictor of NAFLD in obese children and correlates with weight for height, ALT, triglyceride, and HOMA-IR better than each single adipokine.

Ultrasound-propelled nanoporous gold wire for efficient drug loading and release.

Ultrasound (US)-powered nanowire motors based on nanoporous gold segment are developed for increasing the drug loading capacity. The new highly porous nanomotors are characterized with a tunable pore size, high surface area, and high capacity for the drug payload. These nanowire motors are prepared by template membrane deposition of a silver-gold alloy segment followed by dealloying the silver component. The drug doxorubicin (DOX) is loaded within the nanopores via electrostatic interactions with an anionic polymeric coating. The nanoporous gold structure also facilitates the near-infrared (NIR) light controlled release of the drug through photothermal effects. Ultrasound-driven transport of the loaded drug toward cancer cells followed by NIR-light triggered release is illustrated. The incorporation of the nanoporous gold segment leads to a nearly 20-fold increase in the active surface area compared to common gold nanowire motors. It is envisioned that such US-powered nanomotors could provide a new approach to rapidly and efficiently deliver large therapeutic payloads in a target-specific manner.

Effects of pentoxifylline on gentamicin-induced nephrotoxicity.

We aimed to investigate the underlying mechanisms responsible for the renoprotective effects of pentoxifylline (PTX) in gentamicin (GEN)-induced nephropathy. On this purpose, 26 female Wistar rats (200-250 g) were included and four groups were formed. The first one was the control group (n:5). The rats in other groups (n:7 for each) received 50 mg/kg twice daily intraperitoneal (i.p.) PTX, 100 mg/kg i.p. GEN and both GEN and PTX at the same doses for consecutive 8 days, respectively. Rats were weighed both at the beginning and end of the study. After the last dose, 24-hour urines were collected and the rats were sacrificed. Blood samples and kidney tissues were obtained for biochemical, histological, oxidative stress, and apoptotic parameters. Body weights were similar in all groups at the beginning of the study. Rats in GEN group had significant weight loss, tubular damage, and increased apoptosis, while GEN + PTX group had significantly better outcomes. Scr, urinary protein/creatinine, and TBARS levels were significantly higher and Ccr and SOD levels were significantly lower in GEN and GEN + PTX groups in comparison to control and PTX groups, but the levels were similar between GEN and GEN + PTX groups. In conclusion, concomitant administration of PTX provides renoprotection via suppressing apoptosis in GEN-induced nephropathy.

Functionalized ultrasound-propelled magnetically guided nanomotors: toward practical biomedical applications.

Magnetically guided ultrasound-powered nanowire motors, functionalized with bioreceptors and a drug-loaded polymeric segment, are described for "capture and transport" and drug-delivery processes. These high-performance fuel-free motors display advanced capabilities and functionalities, including magnetic guidance, coordinated aligned movement, cargo towing, capture and isolation of biological targets, drug delivery, and operation in real-life biological and environmental media. The template-prepared three-segment Au-Ni-Au nanowire motors are propelled acoustically by mechanical waves produced by a piezoelectric transducer. An embedded nickel segment facilitates a magnetically guided motion as well as transport of large "cargo" along predetermined trajectories. Substantial improvement in the speed and power is realized by the controlled concavity formation at the end of the motor nanowire using a sphere lithography protocol. Functionalization of the Au segments with lectin and antiprotein A antibody bioreceptors allows capture and transport of E. coli and S. aureus bacteria, respectively. Potential therapeutic applications are illustrated in connection to the addition of a pH-sensitive drug-loaded polymeric (PPy-PSS) segment. The attractive capabilities of these fuel-free acoustically driven functionalized Au-Ni-Au nanowires, along with the simple preparation procedure and minimal adverse effects of ultrasonic waves, make them highly attractive for diverse in vivo biomedical applications.

Fabrication of a polyaniline ultramicroelectrode via a self assembled monolayer modified gold electrode.

Herein, we report a simple and inexpensive way for the fabrication of an ultramicroelectrode and present its characterization by electrochemical techniques. The fabrication of polyaniline UME involves only two steps: modification of a gold (Au) electrode by self assembled monolayers (SAM) and then electrodeposition of polyaniline film on this thiol-coated Au electrode by using cyclic voltammetry and constant potential electrolysis methods. Two types of self-assembled monolayers (4-mercapto-1-butanol, MB, and 11-mercaptoundecanoic acid, MUA) were used, respectively, to see the effect of chain length on microelectrode formation. Microelectrode fabrication and utility of the surface was investigated by cyclic voltammetric measurements in a redox probe. The thus prepared polyaniline microelectrode was then used for DNA immobilization. Discrimination between double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) was obtained with enhanced electrochemical signals compared to a polyaniline-coated Au electrode. Different modifications on the electrode surfaces were examined using scanning electron microscopy (SEM).

Cibacron Blue F3GA modified disposable pencil graphite electrode for the investigation of affinity binding to bovine serum albumin.

In this work, Cibacron Blue F3GA (CB) modified pencil graphite electrodes (PGEs) were prepared and their affinities to bovine serum albumin were investigated. Preparation of the PGEs was performed using cyclic voltammetry (CV) and passive adsorption techniques. Improved electrochemical results were obtained with the PGEs prepared by CV technique compared to the PGEs prepared by passive adsorption technique. In order to obtain more sensitive results number of scans used in CV technique and the effect of concentration of CB were studied. Scanning electron microscopy (SEM), atomic force microscopy (AFM) and electrochemical impedance spectroscopy (EIS) were used for the characterization of modified electrodes. The modified PGEs were then used for the electrochemical monitoring of affinity interaction between CB and bovine serum albumin. The effect of BSA concentration and interfering species (tryptophan, glucose and immunoglobulin G) on the response of the electrode were examined. The aim of this study was to prepare an easy, fast, stable and cheap modified electrode for the investigation of the well-known affinity of CB to serum albumin. The electrochemistry can provide alternative routes for dye-protein interaction instead of using classical time-consuming methods.

Electrochemical characterization of redox polymer modified electrode developed for monitoring of adenine.

Electrochemical characterization of redox polymer for monitoring of adenine was described in this study using poly(vinylferrocenium) (PVF(+)) modified platinum (Pt) electrode. Scanning electron microscope (SEM) was used for the surface characterization. The electrochemical behaviors of polymer modified and adenine immobilized polymer modified electrodes were investigated by using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). In order to obtain more sensitive and improved electrochemical signals, analytical parameters such as the effects of polymeric film thickness, immobilization time of adenine, pH and adenine concentration were examined on the response of the polymer modified electrode. Alternating current (AC) impedance spectroscopy was used for the characterization of polymer modified and adenine immobilized polymer modified electrodes. The effect of possible interferents on the response of the electrode was examined.

Self-propelled carbohydrate-sensitive microtransporters with built-in boronic acid recognition for isolating sugars and cells.

A new nanomotor-based target isolation strategy, based on a "built-in" recognition capability, is presented. The concept relies on a poly(3-aminophenylboronic acid) (PAPBA)/Ni/Pt microtube engine coupling the selective monosaccharide recognition of the boronic acid-based outer polymeric layer with the catalytic function of the inner platinum layer. The PAPBA-based microrocket is prepared by membrane-templated electropolymerization of 3-aminophenylboronic acid monomer. The resulting boronic acid-based microengine itself provides the target recognition without the need for additional external functionalization. "On-the-fly" binding and transport of yeast cells (containing sugar residues on their wall) and glucose are illustrated. The use of the recognition polymeric layer does not hinder the efficient propulsion of the microengine in aqueous and physiological media. Release of the captured yeast cells is triggered via a competitive sugar binding involving addition of fructose. No such capture and transport are observed in control experiments involving other cells or microengines. Selective isolation of monosaccharides is illustrated using polystyrene particles loaded with different sugars. Such self-propelled nanomachines with a built-in recognition capability hold considerable promise for diverse applications.