Point-of-Care (POC) testing for biomarker detection demands techniques that are easy to use, readily available, low-cost, and with rapid response times. This paper describes the development of a ...fully open-source, modular, wireless, battery-powered, smartphone-controlled, low-cost potentiostat capable of conducting electrochemical impedance spectroscopy for the electrochemical detection of the S100B protein captured in an ANTI-S100B functionalized thin-film gold interdigitated electrode platform to support traumatic brain injury diagnosis and treatment. EIS results from the developed potentiostat were validated with a commercial benchtop potentiostat by comparing impedance magnitude and phase values along the EIS frequency range. In addition, an experimental design was performed for detecting S100B in spiked human plasma samples with S100B concentrations of clinical utility, and a calibration curve was found for quantifying S100B detection. No statistically significant differences were found between EIS results from the developed potentiostat and the commercial potentiostat. Statistically significant differences in the changes in charge transfer resistance signal between each tested S100B concentration (p < 0.05) were found, with a limit of detection of 35.73 pg/mL. The modularity of the proposed potentiostat allows easier component changes according to the application demands in power, frequency excitation ranges, wireless communication protocol, signal amplification and transduction, precision, and sampling frequency of ADC, among others, when compared to state-of-the-art open-source EIS potentiostats. In addition, the use of minimal, easy acquirable open-source hardware and software, high-level filtering, accurate ADC, Fast Fourier Transform with low spectral leakage, wireless communication, and the simple user interface provides a framework for facilitating EIS analysis and developing new affordable instrumentation for POC biosensors integrated systems.
Chitosan (CS) is a versatile biopolymer used in the fabrication of different types of drug delivery systems. It is recognized mainly by its pH-responsive behavior, mucoadhesive, and membrane ...permeation enhancer properties, which can be explored for modulated drug release and localized delivery. Other biological properties (immune adjuvant, and antitumoral) put this biopolymer at the forefront of raw materials for manufacturing new multifunctional products. Their material attributes can be improved by chemical modification, resulting in CS-based derivatives with controlled hydrophobicity, better solubility, and higher bio(mucoadhesive) capacity. The resultant CS-based materials have been used to fabricate nanoparticles (CS NPs) for the delivery of small molecules and macromolecules into body tissues. Despite many studies that have reported the efficacy and safety of CS NPs, there are still some important issues to be considered before they reach the market. Herein, we demonstrate the perceived risks of using CS NPs can be partially explained by some important gaps in basic science, technological processes, and aspects related to quality control and regulatory affairs. This review discusses the challenges and possible solutions for each of the above-mentioned points with the perspective of enabling CS NPs as technological platforms for the pharmaceutical industry.
Multidrug resistant microorganisms are a growing challenge and new substances that can be useful to treat infections due to these microorganisms are needed. Silver nanoparticle may be a future option ...for treatment of these infections, however, the methods described in vitro to evaluate the inhibitory effect are controversial.
This study evaluated the in vitro activity of silver nanoparticles against 36 susceptible and 54 multidrug resistant Gram-positive and Gram-negative bacteria from clinical sources. The multidrug resistant bacteria were oxacilin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., carbapenem- and polymyxin B-resistant A. baumannii, carbapenem-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae. We analyzed silver nanoparticles stabilized with citrate, chitosan and polyvinyl alcohol and commercial silver nanoparticle. Silver sulfadiazine and silver nitrate were used as control. Different methods were used: agar diffusion, minimum inhibitory concentration, minimum bactericidal concentration and time-kill. The activity of AgNPs using diffusion in solid media and the MIC methods showed similar effect against MDR and antimicrobial-susceptible isolates, with a higher effect against Gram-negative isolates. The better results were achieved with citrate and chitosan silver nanoparticle, both with MIC90 of 6.75 μg mL(-1), which can be due the lower stability of these particles and, consequently, release of Ag(+) ions as revealed by X-ray diffraction (XRD). The bactericidal effect was higher against antimicrobial-susceptible bacteria.
It seems that agar diffusion method can be used as screening test, minimum inhibitory concentration/minimum bactericidal concentration and time kill showed to be useful methods. The activity of commercial silver nanoparticle and silver controls did not exceed the activity of the citrate and chitosan silver nanoparticles. The in vitro inhibitory effect was stronger against Gram-negative than Gram-positive, and similar against multidrug resistant and susceptible bacteria, with best result achieved using citrate and chitosan silver nanoparticles. The bactericidal effect of silver nanoparticle may, in the future, be translated into important therapeutic and clinical options, especially considering the shortage of new antimicrobials against the emerging antimicrobial resistant microorganisms, in particular against Gram-negative bacteria.
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► The geno- and cytotoxicity of gold nanoparticles in cancer and healthy cells were investigated. ► The reactive oxygen species (ROS) generation was evidenced for both cells. ► The ...healthy cells exhibit less sensitive to DNA damage than cancer cells. ► The nanoparticulate systems can be applied in cancer therapy with reduced side effects.
Engineered nanomaterials have been extensively applied as active materials for technological applications. Since the impact of these nanomaterials on health and environment remains undefined, research on their possible toxic effects has attracted considerable attention. It is known that in humans, for example, the primary site of gold nanoparticles (AuNps) accumulation is the liver. The latter has motivated research regarding the use of AuNps for cancer therapy, since specific organs can be target upon appropriate functionalization of specific nanoparticles. In this study, we investigate the geno and cytotoxicity of two types of AuNps against human hepatocellular carcinoma cells (HepG2) and peripheral blood mononuclear cells (PBMC) from healthy human volunteers. The cells were incubated in the presence of different concentrations of AuNps capped with either sodium citrate or polyamidoamine dendrimers (PAMAM). Our results suggest that both types of AuNps interact with HepG2 cells and PBMC and may exhibit in vitro geno and cytotoxicity even at very low concentrations. In addition, the PBMC were less sensitive to DNA damage toxicity effects than cancer HepG2 cells upon exposure to AuNps.
The objective of this study was to formulate and evaluate a unique matrix mixture (nanomiemgel) of nanomicelle and nanoemulsion containing aceclofenac and capsaicin using in vitro and in vivo ...analyses and to compare it to a marketed formulation (Aceproxyvon).
Nanomicelles were prepared using Vitamin E TPGS by solvent evaporation method and nanoemulsion was prepared by high-pressure homogenization method. In vitro drug release and human skin permeation studies were performed and analyzed using HPLC. The efficiency of nanomiemgel as a delivery system was investigated using an imiquimod-induced psoriatic like plaque model developed in C57BL/6 mice.
Atomic Force Microscopy images of the samples exhibited a globular morphology with an average diameter of 200, 250 and 220 nm for NMI, NEM and NMG, respectively. Nanomiemgel demonstrated a controlled release drug pattern and induced 2.02 and 1.97-fold more permeation of aceclofenac and capsaicin, respectively than Aceproxyvon through dermatomed human skin. Nanomiemgel also showed 2.94 and 2.09-fold greater Cmax of aceclofenac and capsaicin, respectively than Aceproxyvon in skin microdialysis study in rats. The PASI score, ear thickness and spleen weight of the imiquimod-induced psoriatic-like plaque model were significantly (p<0.05) reduced in NMG treated mice compared to free drug, NEM, NMI & Aceproxyvon.
Using a new combination of two different drug delivery systems (NEM+NMI), the absorption of the combined system (NMG) was found to be better than either of the individual drug delivery systems due to the utilization of the maximum possible paths of absorption available for that particular drug.
This paper brings an overview of the use of nanostructured films in several types of biosensors, with emphasis on the advantageous control of molecular architecture which is typical of the ...layer-by-layer (LbL) and Langmuir–Blodgett films. Following introductory sections on film fabrication and detection methods, we concentrate on the immobilization of biomolecules on these nanostructured films used in units for biosensing. Important contributions in the literature in biosensors based on electrochemical and optical measurements are highlighted. Furthermore, a discussion is presented on how the concept of electronic tongues has been extended to biosensing, which resulted in increased sensitivity and selectivity. The integration of sensing units with micro-electronics is commented upon, especially in the context of using field-effect transistors (FETs) for biosensing. Examples of LbL and LB films containing proteins, lipids, metallic nanoparticles and carbon nanotubes, which are used for detecting a variety of analytes, will be provided. The prospects for clinical diagnosis with such biosensors are also assessed. Throughout the review, emphasis is placed on the importance of control of molecular architecture, particularly with synergistic combination of organic and inorganic materials. For example, nanostructured films containing capped gold nanoparticles or carbon nanotubes exhibited enhanced performance in biosensing. It is hoped that this survey may assist researchers in choosing materials, molecular architectures, and detection principles, which may be tailored for specific applications.
Neuronal damage secondary to traumatic brain injury (TBI) is a rapidly evolving condition, which requires therapeutic decisions based on the timely identification of clinical deterioration. Changes ...in S100B biomarker levels are associated with TBI severity and patient outcome. The S100B quantification is often difficult since standard immunoassays are time-consuming, costly, and require extensive expertise. A zero-length cross-linking approach on a cysteamine self-assembled monolayer (SAM) was performed to immobilize anti-S100B monoclonal antibodies onto both planar (AuEs) and interdigitated (AuIDEs) gold electrodes via carbonyl-bond. Surface characterization was performed by atomic force microscopy (AFM) and specular-reflectance FTIR for each functionalization step. Biosensor response was studied using the change in charge-transfer resistance (Rct) from electrochemical impedance spectroscopy (EIS) in potassium ferrocyanide, with S100B ranging 10-1000 pg/mL. A single-frequency analysis for capacitances was also performed in AuIDEs. Full factorial designs were applied to assess biosensor sensitivity, specificity, and limit-of-detection (LOD). Higher Rct values were found with increased S100B concentration in both platforms. LODs were 18 pg/mL(AuES) and 6 pg/mL(AuIDEs). AuIDEs provide a simpler manufacturing protocol, with reduced fabrication time and possibly costs, simpler electrochemical response analysis, and could be used for single-frequency analysis for monitoring capacitance changes related to S100B levels.
An electrochemical immunosensor was developed for the determination of apo-Tf (non-iron-bound) and holo-Tf (iron-bound) using polyclonal antibody transferrin (anti-Tf) immobilized at an electrode ...surface as a biorecognition platform. The monitoring was based on the anti-Tf binding with both Tf forms which allows the detection of cancer cells due to the constant iron cycle and the overexpression of anti-Tf on the cancer cell surface. The immunosensor characterization was performed using electrochemical impedance spectroscopy (EIS), which evaluated the impedimetric biorecognition of the antigens-antibody by the use of K
4
Fe(CN)
6
redox group. The immunosensor was able to detect both forms of Tf in terms of charge transfer resistance (
R
ct
). Analytical curves showed a limit of detection of 0.049 and 0.053 ng mL
−1
for apo-Tf and holo-Tf, respectively. The immunosensor was applied to the detection of the two cancer cells A549 (lung carcinoma) and MCF-7 (breast carcinoma) and compared with BHK570, a healthy cell line. The impedimetric response of healthy cells differs significantly from that of the cancerous cells, as revealed by a Dunnett’s test in 95% confidence level—ca. 10
2
cells mL
−1
—indicating the feasibility of the immunosensor to discriminate both types of cells. The indirect detection of anti-Tf based on apo-Tf and holo-Tf binding can be considered an advanced approach for cancer recognition.
Graphical abstract
Gold nanorods (AuNRs) are rod-shaped nanoparticles (NPs) with special optical properties that allow their application in several areas including photothermal therapy, diagnosis, drug and gene ...delivery, cellular imaging, and biosensors. Their high potential for many applications increases the possibility of release in aquatic environments, which can cause risks to organisms. In this study, we evaluated toxic effects of AuNRs on cladoceran and fish (
Ceriodaphnia dubia
and
Danio rerio
) and their recovery after post-exposure periods. The EC
50
of 0.03 mg L
−1
was found for
C. dubia
in the acute exposure. There was a significant decrease in the number of neonates produced and in the filtration rate of
C. dubia
after sub-lethal exposure to AuNRs. The toxic mechanism of these NPs to cladocerans was attributed to increases in the reactive oxygen species (ROS) generation. After 4 h of recovery in clean medium,
C. dubia
were able to reestablish the filtration rate. Enzymatic biomarkers for
D. rerio
showed significant increases in the activity of superoxide dismutase, catalase, and lipid peroxidation after sub-lethal exposure to AuNRs. These biomarkers were recovered after 168 h in clean water. These results are pivotal on the comprehension of AuNR toxicity to aquatic organisms and are useful in assessing this novel nanomaterial impacts on aquatic biota.
Nanomaterials have emerged as promising candidates for cancer therapy and diagnosis as they can solve long-term issues such as drug solubility, systemic distribution, tumor acquired resistance, and ...improve the performance of diagnostic methods. Among inorganic nanomaterials, AgNPs have been extensively studied in the context of cancer treatment and the reported results have raised exciting expectations. In this review, we provide an overview of the recent research on AgNPs antitumoral properties, their application in different cancer treatment modalities, their potential in biosensors development, and also highlight the main challenges and possible strategies to enable its translation to clinical use.
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•An overview of the antitumoral properties of AgNPs and how they can be explored for cancer therapy is provided.•We highlight the novel strategies using AgNPs to improve the performance of biosensors for cancer diagnosis.•The challenges concerning toxicity of AgNPs and the possible strategies to overcome their limitations are presented.