Development of novel focal adhesion kinase (FAK) inhibitors for targeting cancer: Structural insights and therapeutic potential.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase frequently overexpressed in various cancer cells, facilitating tumor growth through the regulation of cell adhesion, migration, and proliferation. Consequently, targeting FAK is considered a promising anti-tumor strategy, particularly for invasive cancers. Numerous potent small-molecule inhibitors have progressed to clinical trials.

Steric Hindrance-Mediated Enzymatic Reaction Enable Homogeneous Dual Fluorescence Indicators Aptasensing of Hepatocellular Carcinoma CTCs.

Circulating tumor cells (CTCs) serve as important biomarkers in the liquid biopsy of hepatocellular carcinoma (HCC). Herein, a homogeneous dual fluorescence indicators aptasensing strategy is described for CTCs in HCC, with the core assistance of a steric hindrance-mediated enzymatic reaction. CTCs in the sample could specifically bind to a 5'-biotin-modified glypican-3 (GPC3) aptamer and remove the steric hindrance formed by the biotin-streptavidin system.

Fructose@histone synergistically improve the performance of DNA-templated Cu NPs: rapid analysis of LAM in tuberculosis urine samples using a handheld fluorometer and a smartphone RGB camera.

This study presented a nanoparticle-enhanced aptamer-recognizing homogeneous detection system combined with a portable instrument (NASPI) to quantify lipoarabinomannan (LAM). This system leveraged the high binding affinity of aptamers, the high sensitivity of nanoparticle cascade amplification, and the stabilization effect of dual stabilizers (fructose and histone), and used probe-Cu to achieve LAM detection at concentrations ranging from 10 ag mL to 100 fg mL, with a limit of detection of 3 ag mL using a fluorometer. It can also be detected using an independently developed handheld fluorometer or the red-green-blue (RGB) camera of a smartphone, with a minimum detection concentration of 10 ag mL.

Self-Assembled DNA Machine and Selective Complexation Recognition Enable Rapid Homogeneous Portable Quantification of Lung Cancer CTCs.

In this study, we systematically investigated the interactions between Cu and various biomolecules, including double-stranded DNA, Y-shaped DNA nanospheres, the double strand of the hybridization chain reaction (HCR), the network structure of cross-linked HCR (cHCR), and small molecules (PPi and His), using Cu as an illustrative example. Our research demonstrated that the coordination between Cu and these biomolecules not only is suitable for modulating luminescent material signals through complexation reactions with Cu but also enhances signal intensities in materials based on chemical reactions by increasing spatial site resistance and local concentration. Building upon these findings, we harnessed the potential for signal amplification in self-assembled DNA nanospheres and the selective complexation modulation of calcein in conjunction with the aptamer targeting mucin 1 as a recognition probe.

Target proteins-regulated DNA nanomachine-electroactive substance complexes enable separation-free electrochemical detection of clinical exosome.

Simple and reliable profiling of tumor-derived exosomes (TDEs) holds significant promise for the early detection of cancer. Nonetheless, this remains challenging owing to the substantial heterogeneity and low concentration of TDEs. Herein, we devised an accurate and highly sensitive electrochemical sensing strategy for TDEs via simultaneously targeting exosomal mucin 1 (MUC1) and programmed cell death ligand 1 (PD-L1).

Insight into small-molecule inhibitors targeting extracellular nucleotide pyrophosphatase/phosphodiesterase1 for potential multiple human diseases.

Extracellular nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been identified as a type II transmembrane glycoprotein. It plays a crucial role in various biological processes, such as bone mineralization, cancer cell proliferation, and immune regulation. Consequently, ENPP1 has garnered attention as a promising target for pharmacological interventions.

Single-Cell Liquid Biopsy of Lung Cancer: Ultra-Simplified Efficient Enrichment of Circulating Tumor Cells and Hand-Held Fluorometer Portable Testing.

Herein, we propose a aper-based aboratory via enzyme-free nucleic acid mplification and nanomaterial-assisted ation exchange reactions (CERs) assisted single-cell-level analysis (PLACS). This method allowed for the rapid detection of mucin 1 and trace circulating tumor cells (CTCs) in the peripheral blood of lung cancer patients. Initially, an independently developed method requiring one centrifuge, two reagents (lymphocyte separation solution and erythrocyte lysate), and a three-step, 45 min sample pretreatment was employed.

Biomolecules-mediated electrochemical signals of Cu: Y-DNA nanomachines enable homogeneous rapid one-step assay of lung cancer circulating tumor cells.

This study presents a straightforward efficient technique for extracting circulating tumor cells (CTCs) and a rapid one-step electrochemical method (45 min) for detecting lung cancer A549 cells based on the specific recognition of mucin 1 using aptamers and the modulation of Cu electrochemical signals by biomolecules. The CTCs separation and enrichment process can be completed within 45 min using lymphocyte separation solution (LSS), erythrocyte lysis solution (ELS), and three centrifugations. Besides, the influence of various biomolecules on Cu electrochemical signals is comprehensively discussed, with DNA nanospheres selected as the medium.

Advancements in dual-target inhibitors of PI3K for tumor therapy: Clinical progress, development strategies, prospects.

Phosphoinositide 3-kinases (PI3Ks) modify lipids by the phosphorylation of inositol phospholipids at the 3'-OH position, thereby participating in signal transduction and exerting effects on various physiological processes such as cell growth, metabolism, and organism development. PI3K activation also drives cancer cell growth, survival, and metabolism, with genetic dysregulation of this pathway observed in diverse human cancers. Therefore, this target is considered a promising potential therapeutic target for various types of cancer.

New Perylene-Based Chemiluminescent Polymer Nanoparticles for Highly Selective Detection of the Superoxide Anion In Vivo.

The superoxide anion (O) is one of the primary reactive oxygen species in biological systems. Developing a determination system for O in vivo has attracted much attention thanks to its complex biological function. Herein, we proposed a new perylene-based chemiluminescence (CL) probe, the SH-PDI polymer, which was capable of generating strong CL signals with O in comparison with other ROS.

Simplified Rapid Enrichment of CTCs and Selective Recognition Prereduction Enable a Homogeneous ICP-MS Liquid Biopsy Strategy of Lung Cancer.

The effective enrichment and hypersensitivity analysis of circulating tumor cells (CTCs) in clinical whole blood samples are highly significant for clinical tumor liquid biopsy. In this study, we established an easy operation and affordable CTCs extraction technique while simultaneously performing the homogeneous inductively coupled plasma mass spectrometry (ICP-MS) determination of CTCs in lung cancer clinical samples based on selective recognition reactions and prereduction phenomena. Our strategy allowed for the pretreatment of whole blood samples in less than 45 min after step-by-step centrifugation, which only required lymphocyte separation solution and erythrocyte lysate.

Novel Near-Infrared Iridium(III) Complex for Chemiluminescence Imaging of Hypochlorous Acid.

Chemiluminescence (CL) probes that possess near-infrared (NIR) emission are highly desirable for in vivo imaging due to their deeper tissue penetration ability and intrinsically high sensitivity. Herein, a novel iridium-based CL probe () with direct NIR emission was reported as the result of hypochlorous acid (HClO)-initiated oxidative deoximation. To improve its biocompatibility and extend the CL time for in vivo imaging applications, this was prepared as a CL nanoparticle probe (s) through encapsulation by an amphiphilic polymer Pluronic F127 (F127).

Endoplasmic Reticulum Peroxynitrite Fluctuations in Hypoxia-Induced Endothelial Injury and Sepsis with a Two-Photon Fluorescence Probe.

Sepsis is a serious systemic inflammatory disease that frequently results in death. Early diagnosis and timely targeted interventions could improve the therapeutic effect. Recent work has revealed that the reactive oxygen species (ROS) in the endoplasmic reticulum (ER) and hypoxia-induced endothelial injury play significant roles in sepsis.

Simultaneous Monitoring of HOCl and Viscosity with Drug-Induced Pyroptosis in Live Cells and Acute Lung Injury.

Pyroptosis is a newly identified form of cell death that is closely correlated with many diseases. Recent studies have indicated that the inflammation in pyroptosis would accelerate the generation of reactive oxygen species (ROS). In addition, intracellular viscosity is another key microenvironmental parameter that reflects many physiological and pathological states in the early stage, hypochlorous acid (HOCl), as an important ROS, also plays significant roles in a variety of pathologies.

A smart probe for simultaneous imaging of the lipid/water microenvironment in atherosclerosis and fatty liver.

A smart lipid droplet specific fluorescent probe (LDs-DM) with dual-emission in water (706 nm) and oil (535 nm) under single-excitation was prepared for revealing the ultra-structure of the aqueous and lipidic microenvironment in living cells, fatty liver tissues and atherosclerotic plaques without fluorescence emission crosstalk. This work is expected to provide inspiration for designing a novel probe with color switching ability.

Two-photon ratiometric fluorescent probe for imaging of hypochlorous acid in acute lung injury and its remediation effect.

Acute lung injury (ALI) is a pulmonary inflammatory disease with high morbidity and mortality rates. However, owing to the unknown etiology and rapid progression of the disease, the diagnosis of ALI is full of challenges with no effective treatment. Since the inflammatory response and oxidative stress played vital roles in the development of ALI, we herein developed the largest emission cross-shift (△λ = 145 nm) two-photon ratiometric fluorescent probe of TPRS-HOCl with high selectivity and short response time toward hypochlorous acid (HOCl) for exploring the relevance between the degree of ALI and HOCl concentration in the development process of the disease.

A Two-Photon Excited Near-Infrared Iridium(III) Complex for Multi-signal Detection and Multimodal Imaging of Hypochlorite.

Hypochlorite (ClO), as a type of reactive oxygen species (ROS), plays a crucial role in the process of oxidative stress and is closely related to many diseases. Thus, developing a method for detecting and imaging of ClO with high sensitivity and selectivity is of great significance. However, the applications of most luminescent probes are limited to the fact that the excitation and emission wavelengths of them are in the visible light region rather than in the near-infrared (NIR) region.

Simultaneous monitoring of polarity changes of lipid droplets and lysosomes with two-photon fluorescent probes.

Intracellular polarity is an essential feature of cell physiological state and abnormal polarity changes of various organelles are related to many diseases. Thus, monitoring of polarity changes of multiple subcellular in living cells contributes to understanding different physiological and pathological processes more accurately. However, most of the previous reports on polarity probes mainly monitored the polarity of a single organelle.

Multifunctional Reduced Graphene Oxide-Based Nanoplatform for Synergistic Targeted Chemo-Photothermal Therapy.

As for cancer treatments, synergistic therapy provides outstanding strategies to facilitate multiple anticancer pathways to induce improved therapeutic efficacy. Here, because of excellent physicochemical and biological properties, tea polyphenol-reduced and functionalized graphene oxide (TPG) was used to develop one single nanoplatform for synergistic targeted photo-chemotherapy. Specifically, a multifunctional nanoplatform with anti-PDL1-conjugated TPG (TPDL1) as a targeted therapy, loading the anticancer drug doxorubicin hydrochloride (DOX) on TPDL1 (TPD) as chemotherapy, and TPDL1 as a photothermal agent with near-infrared (NIR) irradiation as photothermal therapy (PTT) was constructed to reduce side effects and enhance the therapeutic efficacy.

Ratiometric two-photon fluorescent probe for detection of hypochlorite in living cells.

Hypochlorite (ClO) as an important component of reactive oxygen species (ROS), has a close connection to lots of physiological activities, such as signal transmission, maintaining the stability of internal environment, etc. Thus, there is an important meaning to accurately identify and detect ClO with fast response time on biological research. In the study, we designed and synthesized three fluorescent probes with different recognizing moieties for ClO detecting.

Multimodal Imaging Iridium(III) Complex for Hypochlorous Acid in Living Systems.

Biomolecule tracing with different imaging methods is of great significance for more accurately unravelling the fundamental processes in living systems. However, considering the different principles of each imaging method for probe design, it is still a great challenge to apply one molecular probe to achieve two or even more imaging analyses for biomarkers. In general, traditional oxime was reported as a recognition group for fluorescence imaging of HOCl.

Heparan sulfate proteoglycan promotes fibroblast growth factor-2 function for ischemic heart repair.

It is well known that the basic fibroblast growth factor (bFGF) promotes angiogenesis after myocardial infarction (MI), but its biological functions decrease in the event of diffusion, enzymolysis, and weak binding with co-receptors in vivo. Heparan sulfate proteoglycans (HSPG) are a major component of extracellular matrices and have been shown to regulate a wide range of cellular functions and bioprocesses by acting as a co-receptor for bFGF and affecting its bioactivities. However, the influence of HSPG on the function of bFGF after myocardial infarction is unknown.