Alendronate-Functionalized Graphene Quantum Dots as an Effective Fluorescent Sensing Platform for Arsenic Ion Detection.

Alendronate-functionalized graphene quantum dots (ALEN-GQDs) with a quantum yield of 57% were synthesized via a two-step route: preparation of graphene quantum dots (GQDs) by pyrolysis method using citric acid as the carbon source and post functionalization of GQDs via a hydrothermal method with alendronate sodium. After careful characterization of the obtained ALEN-GQDs, they were successfully employed as sensing materials with superior selectivity and sensitivity for the detection of nanomolar levels of arsenic ions (As(III)). According to the mechanistic investigation, arsenic ions can quench the fluorescence intensity of ALEN-GQDs through metal-ligand interaction between the As(III) ions and the surface functional groups of the fluorescent probe. This probe provided a rapid method to monitor As(III) with a wide detection range (44 nM-1.30 µM) and a low detection limit of 13 nM. Finally, to validate the applicability, this novel fluorescent probe was successfully applied for the quantitative determination of As(III) in rice and water samples.

Selective detection of manganese(II) ions based on the fluorescence turn-on response via histidine functionalized carbon quantum dots.

Herein, water-soluble emissive carbon quantum dots (His-CQDs) were synthesized from pyrolysis of sodium citrate in the presence of histidine under hydrothermal conditions. The as-synthesized His-CQDs were characterized using Fourier transform infrared (FT-IR), fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques. The obtained His-CQDs display a strong emission peak at 534 nm when excited at 476 nm with a high quantum yield (61.8 %). The as-synthesized His-CQDs were applied as a new platform for highly selective determination of Mn(II) based on the fluorescence "turn-on" response with a limit of detection of 1.85 µg L-1 (at 3σ) and a linear range of 3.50-35.5 µg L-1 in aqueous solution. The sensing mechanism of the His-CQDs probe for the detection of Mn(II) was studied via density functional theory (DFT), FT-IR, and EDTA complexation methodology. In addition, His-CQDs were successfully applied to determine the accurate amounts of Mn(II) in whole blood control material. More importantly, the integrating such an efficient sensor with point-of-care technology can enable portable, easy-to-use, and rapid sensing systems for better biological and clinical applications.

Fluorescence sensing and imaging with carbon-based quantum dots for early diagnosis of cancer: A review.

This review discusses recent advances and the reported strategies over the last ten years on the use of carbon-based quantum dots (QDs), including carbon dots (CDs), graphene quantum dots (GQDs), and polymer dots (PDs) in the design of fluorescence imaging and biosensing system for early diagnosis of cancers. Besides, this study comprehensively reports the latest developments in these years in the fluorescence imaging (FI) area with special attention to carbon-based QDs that take advantage of the excellent properties offered by these zero-dimensional (0D) nanomaterials as fluorescent tags. The most remarkable advantages of these carbon nanomaterials in the development of fluorescence sensing and imaging strategies compared to the conventional dyes arise from sharp emission spectra, long photostability, low-cost synthesis, reliability, reproducibility, high fluorescent intensity, and high surface functional groups such as carboxyl and amide, which impart better solubility in many solvents and aqueous media and facilitate their easy functionalization with biological species. The final section discusses the main challenges to be met to take full advantage of these properties in fluorescence bio-sensing and imaging as well as the possible future trends in this field based on the great advances that have occurred in recent years.

Nanomaterials-based hyperthermia: A literature review from concept to applications in chemistry and biomedicine.

Hyperthermia, the mild elevation of temperature to 40-45 °C, can induce cancer cell death and enhance the effects of radiotherapy and chemotherapy. Due to the nature of hyperthermia, especially their ability to combine nanotechnology, hyperthermia possesses the potential to open a novel paradigm for the therapeutic strategies. However, achievement of its full potential as a clinically relevant treatment modality has been restricted by its inability to effectively and preferentially heat malignant cells. The main challenge of current hyperthermia treatment is to adequately heat whole volumes of deep-seated tumors without overheating surrounding healthy tissues. So, hyperthermia is under clinical trials (research study with people) and is not widely available. In this Review, we summarize a basic knowledge of hyperthermia before focusing on their applications to the cancer therapy and synthesis. We try to give a comprehensive view of the role of nanomaterials in the designing of hyperthermia-based therapeutic protocols and compare the studies in this field with the purpose of providing a source of helpful information for planning forthcoming hyperthermia researches. However, establishing comparisons between hyperthermia studies is a challenge due to the widely different conditions used by different authors, which, in some cases, is aggravated by the lack of crucial information concerning a certain aspect of the procedure.

Familial Aggregation in Vitamin D Deficiency Disorder.

Introduction The relationship between vitamin D deficiency and some diseases (i.e., heart diseases, malignancies, and infectious diseases) has extensively been studied. There is, however, no epidemiological report on whether the familial predisposing factors have any role in the occurrence of vitamin D deficiency. The aim of this study was to investigate the familial aggregation of vitamin D deficiency disorder in the northwest region of Iran. Materials and Methods A total number of 930 individuals from the general population were invited/registered to the Family Medicine Clinic of Asadabadi Hospital, Tabriz University of Medical Sciences, Iran. A blood sample was obtained from subjects to measure the level of vitamin D. The blood tests were carried out by the enzyme-linked immunosorbent assay method using Biorexfars diagnostics in the Asadabadi Hospital Laboratory. We calculated odds ratio (OR) with 95% confidence intervals (95% CI) to estimate the aggregation of vitamin D deficiency among relatives. Results We ascertained 580 cases with vitamin D deficiency disorder representing an overall prevalence rate of 62.4% (95% CI: 59-65%) in the northwest region. An aggregation of the vitamin D deficiency was found among brothers (OR = 1.55, 95% CI: 0.72-3.32), sisters (OR = 1.24, 95% CI: 0.80-1.93), and spouses (OR = 1.18, 95% CI: 0.76-1.82) of the cases. Other relatives (including parents, grandparents, grandchildren, aunts, nieces, and nephews) showed no aggregation of deficiency in the family in this study. Conclusion Our findings indicated that there might be an aggregational occurrence of vitamin D deficiency in some of the family members. Therefore, to be able to perform early preventive intervention, we would suggest testing the blood level of vitamin D for brothers, sisters, and spouse if one was diagnosed as having vitamin D deficiency.

A nanoscale genosensor for early detection of COVID-19 by voltammetric determination of RNA-dependent RNA polymerase (RdRP) sequence of SARS-CoV-2 virus.

A voltammetric genosensor has been developed for the early diagnosis of COVID-19 by determination of RNA-dependent RNA polymerase (RdRP) sequence as a specific target of novel coronavirus. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses an RdRP for the replication of its genome and the transcription of its genes. Here, the silver ions (Ag+) in the hexathia-18-crown-6 (HT18C6) were used for the first time as a redox probe. Then, the HT18C6(Ag) incorporated carbon paste electrode (CPE) was further modified with chitosan and PAMAM dendrimer-coated silicon quantum dots (SiQDs@PAMAM) for immobilization of probe sequences (aminated oligonucleotides). The current intensity of differential pulse voltammetry using the redox probe was found to decrease with increasing the concentration of target sequence. Based on such signal-off trend, the proposed genosensor exhibited a good linear response to SARS-CoV-2 RdRP in the concentration range 1.0 pM-8.0 nM with a regression equation I (µA) = - 6.555 log [RdRP sequence] (pM) + 32.676 (R2 = 0.995) and a limit of detection (LOD) of 0.3 pM. The standard addition method with different spike concentrations of RdRP sequence in human sputum samples showed a good recovery for real sample analysis (> 95%). Therefore, the developed voltammetric genosensor can be used to determine SARS-CoV-2 RdRP sequence in sputum samples. PAMAM-functionalized SiQDs were used as a versatile electrochemical platform for the SARS-CoV-2 RdRP detection based on a signal off sensing strategy. In this study, for the first time, the silver ions (Ag+) in the hexathia-18-crown-6 carrier were applied as an electrochemical probe.

Dual-modal label-free genosensor based on hemoglobin@gold nanocluster stabilized graphene nanosheets for the electrochemical detection of BCR/ABL fusion gene.

For the first time, we have successfully synthesized stable graphene nanosheets from graphite powder through sonication in the hemoglobin-capped gold nanoclusters (Hb@AuNCs) solution for biosensing application. This approach, as a simple method for the exfoliation and fragmentation of graphite in a nanocluster solution, enabled us to produce stable aqueous graphene dispersions at low cost and without the need for hazardous chemicals or tedious experimental procedures. In this method, Hb@AuNCs were used not only as stabilizing agent of graphene through non-covalent bonding, but also as dispersing agent of few-layer graphene nanosheets. The Hb@AuNCs stabilized graphene (Hb@AuNCs-G) was characterized by high resolution transmission electron microscopy (HRTEM), zeta-sizer and Raman spectroscopy. Then, the graphene nanosheets were applied as a novel versatile electrochemical platform for ultrasensitive biosensing of short DNA species of chronic myelogenous leukemia (CML) based on the "signal off" and "signal on" strategies. For this purpose, a single strand DNA (ssDNA) was immobilized on the Hb@AuNCs-G/AuNPs modified electrode surface and acted as the biorecognition element. Methylene blue (MB), as the signaling probe, was then intercalated into the ssDNA. The intercalated MB was liberated upon interaction with the synthetic complementary DNA (cDNA, target), thereby resulting in the apparent reduction of MB redox signal. This designed "signal off" sensing system enabled the voltammetric determination of the target cDNA over a dynamic linear range (DLR) of 0.1 fM to 10 pM with a limit of detection (LOD) of 0.037 fM. In the "signal on" strategy, the response to the cDNA was detected by monitoring the change in the electron transfer resistance (Rct) using the ferro/ferricyanide system as a redox probe. The charge transfer resistance of the probe was found to increase linearly with increasing concentration of target cDNA in the range of 0.1 fM-10 pM with a limit of detection of 0.030 fM. Finally, the selectivity and feasibility of genosensor was evaluated by the analysis of derived nucleotides from mismatched sequences and the clinical samples of patients with leukemia as real samples, respectively.

Biosensing strategies based on organic-scaffolded metal nanoclusters for ultrasensitive detection of tumor markers.

The recent rapid advances in the synthesis, functionalization and application of nanomaterials have enabled scientists to develop metal nanoclusters (MNCs) stabilized with a variety of scaffolds/protecting ligands including thiols, polymers, proteins, dendrimers and nucleic acids. Considering the unique optical, electronic and physical properties of MNCs, they have been successfully used for the tumor marker biosensing assays. In recent years, the ultrasensitive and accurate detection of tumor markers has been of critical importance for the screening or diagnosis of cancers at their early stages. Nanoclusters have revolutionized the design of biosensors and provided an opportunity for the selective and sensitive determination of tumor markers. Here, we review the synthesis, stabilization and promising applications of fluorescent MNCs, with particular focus on their potential for designing tumor marker biosensors. Finally, the current challenges and future perspectives on the emerging MNC-based biosensors are highlighted as well. Our intended audiences are the broader scientific communities interested in the nanomaterial-based biosensors, and our review paper will, hopefully, open up new horizons for those scientists who manipulae the biological properties of nanoclusters. This review is based on publications available up to January 2020.

Electrochemical genosensor based on carbon nanotube/amine-ionic liquid functionalized reduced graphene oxide nanoplatform for detection of human papillomavirus (HPV16)-related head and neck cancer.

In continuing our effort focused towards the design and development of nanostructured carbon-based biosensors, herein we report an amine-ionic liquid functionalized reduced graphene oxide (NH2-IL-rGO) immunosensing nanoplatform for the electrochemical detection of human papillomavirus (HPV16) DNA in patients with HPV16-positive head and neck cancer (HNC). The model reaction considered in this work was based on grafting of IL to the surface of GO via its silylanization with 3-chloropropyltrimethoxysilane followed by N-alkylation with sodium imidazole salt. Then, the obtained NH2-IL-rGO was immobilized on a multiwalled carbon nanotube (MWCNT) modified electrode surface and, subsequently used for loading aminated DNA probes via covalent bonds by the glutaraldehyde (GA) reagent. In the presence of anthraquinone-2-sulfonic acid monohydrate sodium salt (AQMS) as a redox-active DNA intercalator, the hybridization of ssDNA probes with the target HPV16 DNA strands (complementary strands) led to a significant increase in the genosensor response. The strong specific interaction between the immobilized probe chain and the complementary chain enabled the detection of the HPV16 gene with the differential pulse voltammetry (DPV) measurements. The described method provided an excellent accuracy and good selectivity, compared to the existing methods. This low-cost genosensor can detect ultralow concentrations of HPV16 DNA with a limit of detection of 1.3 nM (at 3σ) and a linear range of 8.5 nM-10.7 µM. To validate the accuracy and performance of method, the extracted clinical sample DNA was used on the pDNA-modified electrode unlike other works that used PCR products.

HIV biosensors for early diagnosis of infection: The intertwine of nanotechnology with sensing strategies.

Human immunodeficiency virus (HIV) is a lentivirus that leads to acquired immunodeficiency syndrome (AIDS). With increasing awareness of AIDS emerging as a global public health threat, different HIV testing kits have been developed to detect antibodies (Ab) directed toward different parts of HIV. A great limitation of these tests is that they can not detect HIV antibodies during early virus infection. Therefore, to overcome this challenge, a wide range of biosensors have been developed for early diagnosis of HIV infection. A significant amount of these studies have been focused on the application of nanomaterials for improving the sensitivity and accuracy of the sensing methods. Following an introduction into this field, a first section of this review covers the synthesis and applicability of such nanomaterials as metal nanoparticles (NPs), quantum dots (QDs), carbon-based nanomaterials and metal nanoclusters (NCs). A second larger section covers the latest developments concerning nanomaterial-based biosensors for HIV diagnosis, with paying a special attention to the determination of CD4+ cells as a hall mark of HIV infection, HIV gene, HIV p24 core protein, HIV p17 peptide, HIV-1 virus-like particles (VLPs) and HIV related enzymes, particularly those that are passed on from the virus to the CD4+ T lymphocytes and are necessary for viral reproduction within the host cell. These studies are described in detail along with their diverse principles/mechanisms (e.g. electrochemistry, fluorescence, electromagnetic-piezoelectric, surface plasmon resonance (SPR), surface enhanced Raman spectroscopy (SERS) and colorimetry). Despite the significant progress in HIV biosensing in the last years, there is a great need for the development of point-of-care (POC) technologies which are affordable, robust, easy to use, portable, and possessing sufficient quantitative accuracy to enable clinical decision making. In the final section, the focus is on the portable sensing devices as a new standard of POC and personalized diagnostics.

An immunosensing device based on inhibition of mediator's faradaic process for early diagnosis of prostate cancer using bifunctional nanoplatform reinforced by carbon nanotube.

In this study, a simple and lable-free voltammetric immunosensor was successfully developed for the ultrasensitive detection of prostate specific antigen (PSA). To do this, multiwalled carbon nanotube (MWCNT)/L-histidine functionalized reduced graphene oxide (His-rGO) was demonstrated as a bifunctional nanoplatform for covalently attaching thionine redox indicator and anti-PSA antibody (Ab). The MWCNT enhanced electrical conductivity and facilitated the electron transfer between thionine and the glassy carbon electrode. While, the presence of anti-PSA antibody blocked the electron transfer of thionine and decreased redox signals. The principle response of proposed immunosensor was based on the selective interaction of PSA with thionine-NH2-GO-COOH-Ab. This selective interaction led to further decrease of response current of attached electrochemical probe. The liner calibration curve for tumor marker determination was 10 fg mL-1-20 ng mL-1 (R2 = 0.996). Under optimized conditions, the immunosensor was able to selectively detect PSA with a limit of detection (LOD) of 2.8 fg mL-1 at 3σ. The relative standard deviations (RSDs) for single-electrode repeatability and electrode-to-electrode reproducibility were less than 2.9% and 5.7% (n = 5), respectively. Furthermore, the as-proposed immunosensor showed excellent performance in detection of PSA in the human serum and saliva samples, which implies that the current strategy has a promising feature for the clinical assessment of tumor marker status in patients with prostate cancer.

A review on nanomaterial-based electrochemical, optical, photoacoustic and magnetoelastic methods for determination of uranyl cation.

This review (with 177 refs) gives an overview on nanomaterial-based methods for the determination of uranyl ion (UO22+) by different types of transducers. Following an introduction into the field, a first large section covers the fundamentals of selective recognition of uranyl ion by receptors such as antibodies, aptamers, DNAzymes, peptides, microorganisms, organic ionophores (such as salophens, catechols, phenanthrolines, annulenes, benzo-substituted macrocyclic diamides, organophosphorus receptors, calixarenes, crown ethers, cryptands and ß-diketones), by ion imprinted polymers, and by functionalized nanomaterials. A second large section covers the various kinds of nanomaterials (NMs) used, specifically on NMs for electrochemical signal amplification, on NMs acting as signal tags or carriers for signal tags, on fluorescent NMs, on NMs for colorimetric assays, on light scattering NMs, on NMs for surface enhanced Raman scattering (SERS)-based assays and wireless magnetoelastic detection systems. We then discuss detection strategies, with subsections on electrochemical methods (including ion-selective and potentiometric systems, voltammetric systems and impedimetric systems). Further sections treat colorimetric, fluorometric, resonance light scattering-based, SERS-based and photoacoustic methods, and wireless magnetoelastic detection. The current state of the art is summarized, and current challenges are discussed at the end. Graphical abstract An overview is given on nanomaterial-based methods for the detection of uranyl ion by different types of transducers (such as electrochemical, optical, photoacoustic, magnetoelastic, etc) along with a critical discussion of their limitations, benefits and application to real samples.

Employing AgNPs doped amidoxime-modified polyacrylonitrile (PAN-oxime) nanofibers for target induced strand displacement-based electrochemical aptasensing of CA125 in ovarian cancer patients.

In this study, a high-performance biosensing nanoplatform based on amidoxime-modified polyacrylonitrile nanofibers decorated with Ag nanoparticles (AgNPs-PAN-oxime NFs) is described. The AgNPs-PAN-oxime NFs were prepared by the combination of electrospinning technique and chemical modification of nitrile group in the PAN. The proposed signal amplifiying nanoplatform was applied in the fabrication of an electrochemical aptasensor for the sensitive detection of CA 125 based on aptamer-cDNA duplex and target induced strand displacement recognition mechanism. The aptasensing interface offers high sensitivity and selectivity for detection of tumor marker due to inherent advantages such as high specific surface area of NFs, good conductivity by doping AgNPs into the polymer NFs and especially the ideal selectivity of anti CA 125 aptamer to its target. The electrochemical aptasensor revealed a wide dynamic linear range (DLR) from 0.01 to 350 U mL-1 with a correlation coefficient of 0.991 and limit of detection (LOD) of 0.0042 U mL-1. Additionally, the designed aptasensor showed acceptable selectivity, reproducibility, repeatability and stability. The satisfactory results for determination of CA 125 in serum samples compared to ELISA method (p-value > 0.05) indicated the potential application of aptasensor in clinical monitoring of tumor biomarker for early diagnosis and management of ovarian cancer.

An overview of nanoscale radionuclides and radiolabeled nanomaterials commonly used for nuclear molecular imaging and therapeutic functions.

Recent advances in the field of nanotechnology applications in nuclear medicine offer the promise of better diagnostic and therapeutic options. In recent years, increasing efforts have been focused on developing nanoconstructs that can be used as core platforms for attaching medical radionuclides with different strategies for the purposes of molecular imaging and targeted drug delivery. This review article presents an introduction to some commonly used nanomaterials with zero-dimensional, one-dimensional, two-dimensional, and three-dimensional structures, describes the various methods applied to radiolabeling of nanomaterials, and provides illustrative examples of application of the nanoscale radionuclides or radiolabeled nanocarriers in nuclear nanomedicine. Especially, the passive and active nanotargeting delivery of radionuclides with illustrating examples for tumor imaging and therapy was reviewed and summarized. The accurate and early diagnosis of cancer can lead to increased survival rates for different types of this disease. Although, the conventional single-modality diagnostic methods such as positron emission tomography/single photon emission computed tomography or MRI used for such purposes are powerful means; most of these are limited by sensitivity or resolution. By integrating complementary signal reporters into a single nanoparticulate contrast agent, multimodal molecular imaging can be performed as scalable images with high sensitivity, resolution, and specificity. The advent of radiolabeled nanocarriers or radioisotope-loaded nanomaterials with magnetic, plasmonic, or fluorescent properties has stimulated growing interest in the developing multimodality imaging probes. These new developments in nuclear nanomedicine are expected to introduce a paradigm shift in multimodal molecular imaging and thereby opening up an era of new diagnostic medical imaging agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 251-285, 2019.

Clinical aspects of radiolabeled aptamers in diagnostic nuclear medicine: A new class of targeted radiopharmaceuticals.

Targeted radiopharmaceuticals offer the possibility of improved imaging with reduced side effects. Up to now, a variety of biological receptors such as aptamers have been successfully radiolabeled and applied to diagnostic imaging of cancers. The concept of using radio-labeled aptamers for binding to their targets has stimulated an immense body of research in diagnostic nuclear medicine. These biological recognition elements are single-stranded oligonucleotides that interact with their target molecules with high affinity and specificity in unique three-dimensional structures. Because of their high affinity and specificity, the receptor-binding aptamers labeled with gamma emitters such as 99mTc, 64Cu, 111In, 18F and 67Ga can facilitate the visualization of receptor-expressing tissues noninvasively. Compared to the antibody-based radiopharmaceuticals, the radiolabeled aptamers provide a number of advantages for clinical diagnostics including high stability, low cost, and ease of production and modification, low immunogenicity and, especially, superior tissue penetration because of their smaller size. In this review, we present recent progresses and challenges in aptamer-based diagnostic radiopharmaceuticals and highlight some representative applications of aptamers in nuclear medicine.

Recent advances in designing nanomaterial based biointerfaces for electrochemical biosensing cardiovascular biomarkers.

Early diagnosis of cardiovascular disease (CVD) is critically important for successful treatment and recovery of patients. At present, detection of CVD at early stages of its progression becomes a major issue for world health. The nanoscale electrochemical biosensors exhibit diverse outstanding properties, rendering them extremely suitable for the determination of CVD biomarkers at very low concentrations in biological fluids. The unique advantages offered by electrochemical biosensors in terms of sensitivity and stability imparted by nanostructuring the electrode surface together with high affinity and selectivity of bioreceptors have led to the development of new electrochemical biosensing strategies that have introduced as interesting alternatives to conventional methodologies for clinical diagnostics of CVD. This review provides an updated overview of selected examples during the period 2005-2018 involving electrochemical biosensing approaches and signal amplification strategies based on nanomaterials, which have been applied for determination of CVD biomarkers. The studied CVD biomarkers include AXL receptor tyrosine kinase, apolipoproteins, cholesterol, C-reactive protein (CRP), D-dimer, fibrinogen (Fib), glucose, insulin, interleukins, lipoproteins, myoglobin, N-terminal pro-B-type natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α) and troponins (Tns) on electrochemical transduction format. Identification of new specific CVD biomarkers, multiplex bioassay for the simultaneous determination of biomarkers, emergence of microfluidic biosensors, real-time analysis of biomarkers and point of care validation with high sensitivity and selectivity are the major challenges for future research.

Advances in the design of nanomaterial-based electrochemical affinity and enzymatic biosensors for metabolic biomarkers: A review.

This review (with 340 refs) focuses on methods for specific and sensitive detection of metabolites for diagnostic purposes, with particular emphasis on electrochemical nanomaterial-based sensors. It also covers novel candidate metabolites as potential biomarkers for diseases such as neurodegenerative diseases, autism spectrum disorder and hepatitis. Following an introduction into the field of metabolic biomarkers, a first major section classifies electrochemical biosensors according to the bioreceptor type (enzymatic, immuno, apta and peptide based sensors). A next section covers applications of nanomaterials in electrochemical biosensing (with subsections on the classification of nanomaterials, electrochemical approaches for signal generation and amplification using nanomaterials, and on nanomaterials as tags). A next large sections treats candidate metabolic biomarkers for diagnosis of diseases (in the context with metabolomics), with subsections on biomarkers for neurodegenerative diseases, autism spectrum disorder and hepatitis. The Conclusion addresses current challenges and future perspectives. Graphical abstract This review focuses on the recent developments in electrochemical biosensors based on the use of nanomaterials for the detection of metabolic biomarkers. It covers the critical metabolites for some diseases such as neurodegenerative diseases, autism spectrum disorder and hepatitis.

Signalling probe displacement electrochemical aptasensor for malignant cell surface nucleolin as a breast cancer biomarker based on gold nanoparticle decorated hydroxyapatite nanorods and silver nanoparticle labels.

Nucleolin is a multifunctional protein that is markedly overexpressed on the surface of most cancer cells. By taking advantage of the high affinity and specificity of the AS1411 aptamer for nucleolin, a signalling probe displacement electrochemical aptasensor was developed. The thiolated AS1411 aptamer was conjugated to hydroxyapatite nanorods (HApNRs) decorated with gold nanoparticles (AuNPs). To further increase the electrical conductivity of the interface, the ionic liquid 1-ethyl-3-methylimidazolium alanine with its high ion conductivity was placed on the electrode surface. Then, the aptamer was immobilized on the modified electrode and conjugated to signalling c-DNA tagged with AgNPs (c-DNA@AgNPs). In the presence of the MCF7 target cells, the signalling probe is displaced and released from the electrode surface. This leads to a decrease in the current that is proportional to the concentration of cancer cells in the range from 10 to 106 cells mL-1, with a detection limit as low as 8 ± 2 cells mL-1 (n = 3) (based as 3σ/m, where σ is the standard deviation of the blank and m is the slope of the calibration plot). This method presents a promising tool for highly sensitive and selective detection of surface nucleolin on MCF7 cancer cells. Graphical abstract HApNR-AuNP-AS1411 aptamer nanocomposite as an electrochemical sensing interface was immobilized on the gold electrode surface and conjugated to signaling c-DNA tagged with AgNPs for determination of surface nucleolin on MCF7 cancer cells.

Recent advances in design of electrochemical affinity biosensors for low level detection of cancer protein biomarkers using nanomaterial-assisted signal enhancement strategies.

The main advances in control and early diagnosis of cancer is greatly aided by low level detection of tumor markers in biological samples. Extensive efforts have been devoted to developing some ultrasensitive electrochemical biosensors for detection of cancer markers with high selectivity. These efforts include the development of the bioreceptors with high specificity and affinity, synthesis of novel signal amplifiers based on nanomaterials and the exploration of appropriate design strategies. Electrochemical measurement protocols are suitable for mass fabrication of miniaturized devices. They have a major role in the move towards rapid and simplified testing for point-of-care usage. This review discusses the remarkable advances of the last 6 years in the electrochemical affinity biosensors for determination of protein and glycoprotein tumor markers, with a particular focus on antibodies and aptamers as biorecognition probes.

A sandwich-type electrochemical immunosensor based on in situ silver deposition for determination of serum level of HER2 in breast cancer patients.

The sensitive quantification of Human Epidermal growth factor Receptor 2 (HER2), as a key prognostic tumor marker, plays a critical role in screening, early diagnosis and management of breast cancer. This paper describes a sandwich-type immunoassay with silver signal enhancement strategy for highly sensitive detection of HER2. For this purpose, the target capturing step was designed by functionalization of 3-aminopropyltrimethoxysilane coated magnetite nanoparticles with antibody (antiHER2/APTMS-Fe3O4), as a platform bioconjugate (PB), and immobilized at a bare GCE. Then, in the presence of label-free immunosensor, the PB was covered by magnetic gold nanoparticles self-assembled with thiolated antibodies (antiHER2/Hyd@AuNPs-APTMS-Fe3O4) containing chemically reduced silver ions, as a label bioconjugate (LB). Under optimum conditions, a linear relationship between the differential pulse voltammetric (DPV) stripping signal of silver and the logarithm of HER2 concentrations was obtained in the range of 5.0 × 10-4-50.0ngmL-1 (R2 = 0.9906) with a detection limit of 2.0 × 10-5ngmL-1. The effectiveness of this protocol was evaluated experimentally through employing of designed immunosensor for detection of the serum level of tumor marker. The good consistency of the results with those obtained by the enzyme-linked immunosorbent assay (ELISA) conventional method (p-value of < 0.05) showed that this immunosensor can be applied for the testing of HER2 in clinical samples of breast cancer patients.