pH-Activatable Molecular Probe for COX-2 Imaging in Human Oral Squamous Carcinoma Cells and Patient-Derived Tissues.

For developing a successful cancer therapeutic modality, the early precise detection of cancer cells in patient biopsies in oral squamous cell carcinoma (OSCC) is crucial. This could help researchers create new diagnostic and therapeutic tools and assist clinicians in recommending more effective treatment plans and improving patient survival. We have developed an SMPD, cyclooxygenase-2 (COX-2) targeting pH-activable fluorophore named , combining a potent COX-2 inhibitor, celecoxib, linked to a naphthalimide fluorophore with an acidic microenvironment-responsive piperazine moiety for specific optical imaging of OSCC in cells and patient tissues.

Rational fragment-based design of compounds targeting the PWWP domain of the HRP family.

Lens epithelium-derived growth factor p75 (LEDGF/p75), member of the hepatoma-derived growth-factor-related protein (HRP) family, is a transcriptional co-activator and involved in several pathologies including HIV infection and malignancies such as MLL-rearranged leukemia. LEDGF/p75 acts by tethering proteins to the chromatin through its integrase binding domain. This chromatin interaction occurs between the PWWP domain of LEDGF/p75 and nucleosomes carrying a di- or trimethylation mark on histone H3 Lys36 (H3K36me2/3).

Theranostic Fluorescent Probes.

The ability to gain spatiotemporal information, and in some cases achieve spatiotemporal control, in the context of drug delivery makes theranostic fluorescent probes an attractive and intensely investigated research topic. This interest is reflected in the steep rise in publications on the topic that have appeared over the past decade. Theranostic fluorescent probes, in their various incarnations, generally comprise a fluorophore linked to a masked drug, in which the drug is released as the result of certain stimuli, with both intrinsic and extrinsic stimuli being reported.

Targeting chemokine receptors from the inside-out: discovery and development of small-molecule intracellular antagonists.

Ever since the first biologically active chemokines were discovered in the late 1980s, these messenger proteins and their receptors have been the target for a plethora of drug discovery efforts in the pharmaceutical industry, as well as in academia. Owing to the publication of several chemokine receptor X-ray crystal structures, a highly druggable, intracellular, allosteric binding site which partially overlaps with the G protein binding site was discovered. This intriguing, new approach for chemokine receptor antagonism has captured researchers around the world, pushing the exploration of this intracellular binding site and new antagonists thereof.

Picomolar-sensitive β-amyloid fibril fluorophores by tailoring the hydrophobicity of biannulated π-elongated dioxaborine-dyes.

The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities.

Calix[]triazolium based turn-on fluorescent sensing ensemble for selective adenosine monophosphate (AMP) detection.

A novel calix[]triazolium was synthesized and exhibited excellent selectivity for AMP. The binding between calix[]triazolium and chromenolate anions forms a non-fluorescent complex and the resulting supramolecular ensemble selectively detects AMP in water and induces "turn-on" fluorescence. The sensing platform is the first macrocyclic system to discriminate AMP from ADP and ATP through fluorescence changes.

Data driven evaluation of healthy volunteer characteristics at screening for phase I clinical trials to inform on study design and optimize screening processes.

Protocols for clinical trials describe inclusion and exclusion criteria based on general and compound-specific considerations to ensure subject safety and data quality. In phase I clinical trials, healthy volunteers (HVs) are screened against these criteria that often specify predefined eligibility ranges for vital signs, electrocardiogram, and laboratory tests. HVs are excluded if baseline parameters deviate from these ranges even though this may not indicate underlying pathology, which could delay trial execution.

A Small Molecule Strategy for Targeting Cancer Stem Cells in Hypoxic Microenvironments and Preventing Tumorigenesis.

Breast cancer consists of heterogenic subpopulations, which determine the prognosis and response to chemotherapy. Among these subpopulations, a very limited number of cancer cells are particularly problematic. These cells, known as breast cancer stem cells (BCSCs), are thought responsible for metastasis and recurrence.

Human Glioblastoma Visualization: Triple Receptor-Targeting Fluorescent Complex of Dye, SIWV Tetra-Peptide, and Serum Albumin Protein.

Fluorescence guided surgery (FGS) has been highlighted in the clinical site for guiding surgical procedures and providing the surgeon with a real-time visualization of the operating field. FGS is a powerful technique for precise surgery, particularly tumor resection; however, clinically approved fluorescent dyes have often shown several limitations during FGS, such as non-tumor-targeting, low in vivo stability, insufficient emission intensity, and low blood-brain barrier penetration. In this study, we disclose a fluorescent dye complex, peptide, and protein for the targeted visualization of human glioblastoma (GBM) cells and tissues.

Mitochondrial relocation of a common synthetic antibiotic: A non-genotoxic approach to cancer therapy.

Tumor recurrence as a result of therapy-induced nuclear DNA lesions is a major issue in cancer treatment. Currently, only a few examples of potentially non-genotoxic drugs have been reported. Mitochondrial re-localization of ciprofloxacin, one of the most commonly prescribed synthetic antibiotics, is reported here as a new approach.

Visualizing mitochondria and mouse intestine with a fluorescent complex of a naphthalene-based dipolar dye and serum albumin.

We have explored a new research field of fluorophores through the manipulation of fluorophore-binding proteins. The development of a new imaging agent for tracing a specific organelle or a particular site within a living organism has been of great interest in the field of basic science as well as translational medicine. In this work and for the first time, we will disclose a new naphthalene-based dipolar dye and its complex, with serum albumin (SA), and show their applicability for the selective imaging of mitochondria in cells and the intestine in a mouse.

Combining viscosity-restricted intramolecular motion and mitochondrial targeting leads to selective tumor visualization.

We report a novel fluorescent molecular conjugate, V-M1, enabling an accurate visualization of tumor tissues. The emission wavelength of V-M1 exceeds 650 nm, which is well within the near-infrared therapeutic window. Tumor accumulation of this cationic dye allows the visualization of cancerous cells as a function of mitochondrial viscosity.

STORM imaging of mitochondrial dynamics using a vicinal-dithiol-proteins-targeted probe.

Stochastic optical reconstruction microscopy (STORM) is a promising method for the visualization of ultra-fine mitochondrial structures. However, this approach is limited to monitoring dynamic intracellular events owing to its low temporal resolution. We developed a new strategy to capture mitochondrial dynamics using a compressed sensing STORM algorithm following raw data pre-treatments by a noise-corrected principal component analysis and K-factor image factorization.

MDM2-Associated Clusterization-Triggered Emission and Apoptosis Induction Effectuated by a Theranostic Spiropolymer.

Heteroatom-containing spiropolymers were constructed in a facile manner by a catalyst-free multicomponent spiropolymerization route. P1a2b as the most potent of these spiropolymers, demonstrates cluster-triggered emission resulting from strong interactions with the MDM2 protein. By preventing the anti-apoptotic p53/MDM2 interaction, P1a2b triggers apoptosis in cancerous cells, while demonstrating a good biocompatibility and non-toxicity in non-cancerous cells.

Crown ether-appended calix[2]triazolium[2]arene as a macrocyclic receptor for the recognition of the HPO anion.

A crown ether-appended calix[2]triazolium[2]arene, which exhibits excellent selectivity for HPO compared to other anions, has been designed and synthesized. The selectivity of the prepared receptor for HPO is caused by the stabilization of HPO by the neighboring triazolium hydrogen bond donors and crown ether hydrogen bond acceptors.

Nanomolar detection of adenosine triphosphate (ATP) using a nanostructured fluorescent chemosensing ensemble.

We report a novel nanostructured chemosensing ensemble PyNp-C13/UD, obtained by self-assembling uranine dye (UD) and an amphiphilic pyridinium salt PyNp-C13. The ensemble was developed for the fluorescence turn-on sensing of ATP in aqueous solutions and inside living cells. The assembly operates via an indicator displacement assay (IDA) method with an ultra-low detection limit of 6.

In Vitro Activation of Cytochrome P450 46A1 (CYP46A1) by Efavirenz-Related Compounds.

Cytochrome P450 46A1 (CYP46A1) is a central nervous system-specific enzyme, which catalyzes cholesterol 24-hydroxylation. Currently CYP46A1 is being evaluated in a clinical trial for activation by small doses of the anti-HIV drug efavirenz. Eight efavirenz-related compounds were investigated for CYP46A1 activation in vitro, induction of a CYP46A1 spectral response, spectral values, interaction with the P450 allosteric sites, and a model of binding to the enzyme active site.

Revealing Protein Aggregates under Thapsigargin-Induced ER Stress Using an ER-Targeted Thioflavin.

Endoplasmic reticulum-thioflavin T ), a thioflavin T-based fluorescent chemosensor, was developed to detect protein aggregates in the endoplasmic reticulum (ER) and was applied to live cells under various forms of ER stress. Upon dithiothreitol (DTT)-induced reductive denaturation of lysozyme and albumin, the intensity was increased in a protein concentration-dependent way, following a nonfluorescent lag phase. detects protein aggregates rather than unfolded proteins in solution, and the protein aggregation can be visualized in the presence of lipid membranes or native proteins.

Enhanced sensitivity of fluorescence-based Fe(ii) detection by freezing.

The first example of combining the fluorescent probe-based freeze concentration effect with N-oxide chemistry is reported for the highly sensitive and selective detection of ferrous ion (Fe(ii)). Interestingly, our preliminary results demonstrated that the fluorescence intensity of Fe(ii) was markedly enhanced upon freezing, and the location of Fe(ii) in the freezing state was visualized by confocal microscopy using a cryostage.

Ultrasensitive electrochemical genosensor for direct detection of specific RNA sequences derived from avian influenza viruses present in biological samples.

An electrochemical genosensor based on an epoxy-phenanthroline-Fe(III)-NH2-ssDNA layer for the detection of RNA derived from Avian Influenza is presented. The biosensor preparation consists of: (I) modification of gold electrodes with aminoethanethiol, (II) modification of the self-assembled monolayer of aminoethanethiol with 5,6-epoxy-5,6-dihydro-[1,10]-phenanthroline using "click" chemistry, (III) a first step of complexation of Fe(III) by 5,6-epoxy-5,6-dihydro-[1,10]-phenanthroline, (IV) a second step of complexation of Fe(III) by 5,6-epoxy-5,6-dihydro-[1,10]-phenanthroline, (V) immobilization of the single stranded amino-DNA probe via "click" chemistry between epoxy and amino groups. The interactions between the ssDNA probe and RNA targets were explored with Osteryoung Square Wave Voltammetry.

A colorimetric and fluorescent lighting-up sensor based on ICT coupled with PET for rapid, specific and sensitive detection of nitrite in food.

An anthracene carboxyimide derivative was synthesized as a colorimetric and fluorogenic sensor to determine NO with a rapid response (<4 min), excellent selectivity and a low detection limit (84 nM). Paper strips containing the sensor were applied to visually determine the NO content in food.

Coumarin-Based Small-Molecule Fluorescent Chemosensors.

Coumarins are a very large family of compounds containing the unique 2-chromen-2-one motif, as it is known according to IUPAC nomenclature. Coumarin derivatives are widely found in nature, especially in plants and are constituents of several essential oils. Up to now, thousands of coumarin derivatives have been isolated from nature or produced by chemists.

Harnessing Intramolecular Rotation To Enhance Two-photon Imaging of Aβ Plaques through Minimizing Background Fluorescence.

The aggregation of amyloid beta (Aβ) proteins in senile plaques is a critical event during the development of Alzheimer's disease, and the postmortem detection of Aβ-rich proteinaceous deposits through fluorescent staining remains one of the most robust diagnostic tools. In animal models, fluorescence imaging can be employed to follow the progression of the disease, and among the different imaging methods, two-photon microscopy (TPM) has emerged as one of the most powerful. To date, several near-infrared-emissive two-photon dyes with a high affinity for Aβ fibrils have been developed, but there has often been a tradeoff between excellent two-photon cross-sections and large fluorescence signal-to-background ratios.