Superparamagnetic iron oxide nanoparticles (SPIONs) and luminescent semiconductor quantum dots (QDs) have been at the center of biomedicinal research in the last decades, utilized for imaging, diagnostics, and therapy. SPIONs are known and utilized for magnetic resonance imaging (MRI), magnetic hyperthermia and photothermal therapy (PTT) and drug delivery [1, 2]. QDs, on the other hand, are very well established in the bioimaging and theranostics as an alternative to organic fluorophores due to their unique properties such as narrow emission bands, size-tunable and strong fluorescence and excellent photostability [3, 4]. Light-induced localized therapies, namely photodynamic therapy (PDT) and PTT, emerge as an alternative and/or complementary treatments along with conventional chemotherapy in the field of cancer therapeutics [5, 6]. Hybrid nanoparticles composed of magnetic-luminescent properties are highly appealing as they provide dual-imaging ability and enhanced photothermal properties, along with being excellent drug delivery vehicles [7]. In this study, luminescent-superparamagnetic Ag2S-Fe3O4 (AS-SPION) hybrid nanoparticles were developed via a simple ligand exchange method using 2-mercaptopropionic acid (2-MPA) coated AS QDs replacing lauric acid (LA) coating on SPIONs. Synthesis of both particles and the hybrids were previously reported [8, 9]. Final hybrids were then loaded with 5-aminolevulinic acid (5-ALA), which is an FDA approved natural precursor of PDT agent protoporphyrin IX (PPIX), to achieve imaging guided enhanced PDT-PTT combination therapy on prostate cancer cells. By loading 5-ALA to nanoparticles, its bioavailability and the efficiency of the combination therapy can be increased. The hydrodynamic size of the hybrids were less than 100 nm and they had strong emission in the medical imaging window (850-900 nm). The comparative PTT potential of the QDs vs. hybrids were initially investigated in the solution by irradiating the samples at 640 nm (215 mW) and 808 nm (400 mW) at different Ag concentrations. After determining the optimal PTT conditions in the solution, followed by in-vitro dark cytotoxicity of AS-2MPA QDs, AS-SPION hybrids, free ALA, and AS-SPION-ALA particles for LnCap, PC3 and Du145 cell lines, best treatment parameters were defined. Additionally, L929 cells were used to prove the non-toxic nature of the particles. PDT-PTT combination therapy was applied via co-irradiation of the cells with 640 and 808 nm laser at 300 mW and 700 mW power, respectively, for 5 minutes and cell death was evaluated with standard MTT assay. Additionally, cell death mechanisms were investigated in terms of ROS generation, apoptosis/necrosis and live/dead imaging. This study was focused on the determination of advantages of having hybrid nanoparticles providing dual-modality, enhanced phototherapy effect and the difference generated from combination therapy in comparison to monotherapies in the treatment of prostate cancer.

A cysteine (Cys) activatable chlorinated hemicyanine (Cl-Cys) was introduced as a tumour selective image-guided dual phototherapy agent. Cl-Cys exhibited a significant turn on response in its near-IR emission signal and activated its singlet oxygen generation as well as photothermal conversion potentials upon reacting with Cys. The laser irradiation of Cl-Cys induced significant cell death in cancer cells with high Cys level, while it stayed deactivated and non-emissive in a healthy cell line. A profound synergistic PDT/PTT effect was observed at high doses. Remarkably, Cl-Cys marks the first ever example of Cys-responsive small organic-based therapeutic agent and holds a great promise to develop new activity-based photosensitizers for dual phototherapy action.

eIF3d is a protein biomarker which has a potential for the diagnosis of various cancers. Herein, a bio-platform was constructed for eIF3d sensing by using LSG and surface functionalization with anti eIF3d antibody via EDC/NHS chemistry. Following the surface modifications, XPS and several electrochemical methods were used. Difference in the signals were related to biomarker amounts between 75-500 ng/mL. LOD was calculated as 50.4 ng/mL. Selectivity of biosensor was tested by using of various interference molecules. EIF3d was also successfully detected in synthetic biological samples. Thus, to the best of our knowledge, this study is one of the rare studies on use of LSGs in immunosensor studies.

Phototherapies, in the form of photodynamic therapy (PDT) and photothermal therapy (PTT), are very promising treatment modalities for cancer since they provide locality and turn-on mechanism for toxicity, both of which are critical in reducing off-site toxicity. Irradiation of photosensitive agents demonstrated successful therapeutic outcomes; however, each approach has its limitations and needs to be improved for clinical success. The combination of PTT and PDT may work in a synergistic way to overcome the limitations of each method and indeed improve the treatment efficacy. The development of single photosensitive agents capable of inducing both PDT and PTT is, therefore, extremely advantageous and highly desired. Cyanine dyes are shown to have such potential, hence have been very popular in the recent years. Luminescence of cyanine dyes renders them as phototheranostic molecules, reporting the localization of the photosensitive agent prior to irradiation to induce phototoxicity, hence allowing image-guided phototherapy. In this review, we mainly focus on the cyanine dye–based phototherapy of different cancer cells, concentrating on the advancements achieved in the last ten years.

The cover image is based on the Full Paper Laser-scribed Graphene Electrodes as an Electrochemical Immunosensing Platform for Cancer Biomarker ‘eIF3d' by Simge Balaban et al., DOI: 10.1002/elan.202060482.

Herein, we first constructed a functional surface using a catechol-attached polypeptide (CtP) for the detection of JWH-018 (N-4-hydroxypentyl metabolite). K2 antibody was then incorporated to the polymer via covalent cross-linker. Step-by-step modifications on the glassy carbon electrode surface were characterized by electrochemical measurements such as differential pulse voltammetry, cyclic voltammetry, impedance spectroscopy, and X-ray photoelectron spectroscopy. Linearity and the limit of detection for JWH-018 (N-4-hydroxypentyl metabolite) were determined as 10-500 ng/mL with an equation of y = 0.0018x + 0.136 (R-2 = 0.993) and 5.892 ng/mL, respectively. The selectivity of the biosensor was evaluated with different interfering molecules (methamphetamine, codeine, and cocaine). Finally, the biosensor was successfully used in the determination of JWH-018 (N-4-hydroxypentyl metabolite) in spiked synthetic urine samples, and a high-performance liquid chromatography (HPLC) system was used as a reference method to confirm the sample application. The results show that this biosensor platform can be applied to detect other JWH series of synthetic cannabinoids with high sensitivity and accuracy.

INTRODUCTION:The importance of biomarkers for pharmaceutical drug development and clinical diagnostics is more significant than ever in the current shift toward personalized medicine. Biomarkers have taken a central position either as companion markers to support drug development and patient selection, or as indicators aiming to detect the earliest perturbations indicative of disease, minimizing therapeutic intervention or even enabling disease reversal. Protein biomarkers are of particular interest given their central role in biochemical pathways. Hence, capabilities to analyze multiple protein biomarkers in one assay are highly interesting for biomedical research.AREAS COVERED:We here review multiple methods that are suitable for robust, high throughput, standardized, and affordable analysis of protein biomarkers in a multiplex format. We describe innovative developments in immunoassays, the vanguard of methods in clinical laboratories, and mass spectrometry, increasingly implemented for protein biomarker analysis. Moreover, emerging techniques are discussed with potentially improved protein capture, separation, and detection that will further boost multiplex analyses.EXPERT COMMENTARY:The development of clinically applied multiplex protein biomarker assays is essential as multi-protein signatures provide more comprehensive information about biological systems than single biomarkers, leading to improved insights in mechanisms of disease, diagnostics, and the effect of personalized medicine.

The need for a continuous, real-time monitoring of specific diseases represents an unmet scientific need. Evidently, cancer is one of the most important diseases where it is crucial to increase the rates of patient survival and monitor disease prognosis. Herein, a novel type of immunoassay was developed for detection of cancer biomarkers, using alpha-fetoprotein (AFP) and mucin-16 (MUC16) as model analytes. Using gold nanoparticle (AuNP) bioconjugates as a signal production tool, relevant antibody (Ab)-conjugated AuNPs were prepared on the nitrocellulose (NC) membrane. To construct a spot-like point-of-care (POC) immunoassay, cysteamine conjugated AuNPs (AuNP-Cys) were immobilized on the NC membrane and antibodies were conjugated to the nanoparticle on the detection pad, following a treatment with the samples that contains AFP or MUC16 which are well-known protein biomarkers for liver and ovarian cancer. By using the change in the colorimetric properties of AuNPs, detection of tumor markers was achieved by using a smartphone image and color analysis software at the final stage. Image J application was used for the evaluation of color changes depending on the biomarker concentration in buffer or spiked synthetic serum samples. The linear range was found as 0.1 ng/mL-100 ng/mL for AFP and 0.1-10 ng/mL for MUC16. Limit-of-detection (LOA) was calculated as 1.054 ng/mL and 0.413 ng/mL for AFP and MUC16, respectively. Interferent molecules, Her2, Immunoglobulin G (IgG) and bovine serum albumin (BSA) were tested on the system. Furthermore, synthetic serum samples spiked with selected analyte molecule were applied on the system and measured successfully.

Endogenous steroids such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) have commonly used as doping materials by athletes and to date novel techniques are needed for detection of these molecules. In this study, antibody-based electrochemical biosensor has developed for testing level of the DHEA-S. For this aim, gold surfaces were initially modified with cysteamine (Cys) and then, DHEA-S antibody was immobilized on the surface via glutaraldehyde (GA) as a crosslinking agent. The stepwise modification of electrode surface was monitored by using various electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Linear range was determined as 2.5-100 ng/mL DHEA-S using differential pulse voltammetry (DPV) technique, as well. Moreover, repeatability (+/- S.D.), coefficient of variation (%) and limit of detection (LOD) values were calculated as 0.033, 1.030 and 3.971, respectively. Also, DHEA-S in synthetic serum and urine samples were successfully determined with standard addition method and confirmation analysis were performed with liquid chromatography quadrupole-time of flight mass spectrometry (LC-QTOF/MS) system. The selectivity was studied with the addition of some interfering molecules (testosterone, bovine serum albumin (BSA), cholesterol, uric acid, lactic acid, codein (COD), ascorbic acid, DHEA). Consequently, this work is proposed as practical, innovative and cost-effective technique that can be easily adapted for the miniaturized form for the analysis of other doping substances as well as DHEA-S for the future works.

In this Feature, the most recent developments as well as "pros and cons" in smartphone sensing, which have been developed using various functional nanoparticles in paper-based sensing systems, will be discussed. Additionally, smart phone sensing and POC combination as a potential tool that opens a gate for knowledge flow "from lab scale data to public use" will be evaluated.

Introduction: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and associated with decreased lung function and inflammation. The heterogeneity of COPD and its molecular and clinical features hinder efficient patient stratification and introduction of personalized therapeutic approaches. The available clinical tools do not efficiently predict the progression and exacerbations of the disease. Areas covered: An overview of the most recent studies on putative COPD protein biomarkers and the challenges for implementing their use in the clinical setting is presented. Expert commentary: Proteomics biomarker discovery in COPD has mostly focused on approaches evaluating specific proteins on a limited number of samples. The most promising protein candidates can be classified into five main biological categories: extracellular matrix (ECM) remodeling, inflammation/immune response, oxidative stress response, vascular tone regulation, and lipid metabolism. To efficiently stratify COPD patients and predict exacerbations, it will be necessary to implement biomarker panels to better represent the complex pathophysiology of this disease. The application of unbiased proteomics and bioinformatics followed by appropriate clinical validation studies will contribute to the achievement of this aim while increasing the number of validated biomarkers that can enter the qualification processes by the regulatory entities.

During the last decade, progress has been made in the on-site detection of abused drug use. Herein, we present an electrochemical biosensor for the detection of one of the synthetic cannabinoids (SCs), JWH-073, using poly (methyl methacrylate) (PMMA) hyperbranched copolymer (HBC) as a base coating and antibody molecules to bind the JWH-073 to the surface. Modification of the surface is proved with various techniques such as differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectrometry. The limit of detection and linearity (in logarithmic scale) for JWH-073 were found to be 31.87 ng/mL and 25-500 ng/mL, respectively. The selectivity of the proposed biosensor was also tested in the presence of interfering molecules and the response was much higher for JWH-073 in all measurements. In the final part of the study, synthetic urine was tested with the device and the relative standard deviation value was calculated to be less than 5.0%. The confirmation of data from the resulting bio-platform was performed via LC-QTOF/MS. This work is the first of its kind, a novel, rapid, cost-effective sensing platform for the detection of the SC.

A novel catechol-bearing polypeptide (CtP) was synthesized and used as a component of electrochemical biosensor involving both enzymatic activity and affinity-based sensing systems. Glucose oxidase (GOx) and anti-immunoglobulin G (Anti-IgG) were selected as model biorecognition elements for the selective analysis of glucose and IgG. Step-by-step surface modifications were followed using various techniques such as cyclic voltammetry (CV) and electrochemical impedance spectrometry (EIS) as well as X-ray photoelectron spectroscopy (XPS). Additionally, contact angles were measured in order to observe surface properties. Amperometric measurements using the GOx biosensor were performed at -0.7 V by following the oxygen consumption due to the enzymatic reaction in different glucose concentrations. Affinity-based interactions via IgG sensor were monitored using the differential pulse voltammetry (DPV) technique. As the "surface design with CtP" approach employed herein is generally applicable and easily adaptable to obtain functional matrices for biomolecule immobilization, CtP-coated surfaces can be promising platforms for the fabrication of various biobased sensing systems.