Development of a cysteine responsive chlorinated hemicyanine for image-guided dual phototherapy.

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.

Analytical techniques for multiplex analysis of protein biomarkers.

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.

Paper-based colorimetric spot test utilizing smartphone sensing for detection of biomarkers.

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 (LOD) 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.

Systematic review on recent potential biomarkers of chronic obstructive pulmonary disease.

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.

Paper-Based Analytical Methods for Smartphone Sensing with Functional Nanoparticles: Bridges from Smart Surfaces to Global Health.

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.

Surface Modification with a Catechol-Bearing Polypeptide and Sensing Applications.

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.