Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy.

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function and contributes to immunotherapy failure. However, acidic conditions in the TME disrupt the interaction between cancer and immune cells, driving tumor-infiltrating T cells and NK cells into an inactivated, anergic state.

Immunotherapy Enhancement by Targeting Extracellular Tumor pH in Triple-Negative Breast Cancer Mouse Model.

Triple-negative breast cancer (TNBC), as one of the most aggressive forms of breast cancer, is characterized by a poor prognosis and a very low rate of disease-free and overall survival. In recent years, immunotherapeutic approaches targeting T cell checkpoint molecules, such as cytotoxic lymphocyte antigen-4 (CTLA-4), programmed death1 (PD-1) or its ligand, programmed death ligand 1 (PD-L1), have shown great potential and have been used to treat various cancers as single therapies or in combination with other modalities. However, despite this remarkable progress, patients with TNBC have shown a low response rate to this approach, commonly developing resistance to immune checkpoint blockade, leading to treatment failure.

Development of Curcumin and Piperine-Loaded Bio-Active Self-Nanoemulsifying Drugs and Investigation of Their Bioactivity in Zebrafish Embryos and Human Hematological Cancer Cell Lines.

Purpose: Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy.

Methods: CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature.

Energy Harvesting by Mesoporous Reduced Graphene Oxide Enhanced the Mediator-Free Glucose-Powered Enzymatic Biofuel Cell for Biomedical Applications.

Harnessing electrochemical energy in an engineered electrical circuit from biochemical substrates in the human body using biofuel cells is gaining increasing research attention in the current decade due to the wide range of biomedical possibilities it creates for electronic devices. In this report, we describe and characterize the construction of just such an enzymatic biofuel cell (EBFC). It is simple, mediator-free, and glucose-powered, employing only biocompatible materials.

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin.

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.

Sensitive Detection of Thiourea Hazardous Toxin with Sandwich-Type Nafion/CuO/ZnO Nanospikes/Glassy Carbon Composite Electrodes.

In this research study, we developed a voltammetric electrochemical sensor probe with a copolymer Nafion () decorated with hydrothermally prepared sandwich-type CuO/ZnO nanospikes (NSs) onto a glassy carbon electrode (GCE) for reliable thiourea (TU) detection. The detailed characterizations in terms of structural morphology, binding energy, elemental compositions, grain size and crystallinity for synthesized NSs were performed by field emission scanning electron microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD) analysis, respectively. The differential pulse voltammetric (DPV) analysis for TU showed good linearity at current-versus-TU concentration on the calibration plot in the 0.

Dendrimer-Based Nanomedicine (Paramagnetic Nanoparticle, Nanocombretastatin, Nanocurcumin) for Glioblastoma Multiforme Imaging and Therapy.

In brain tumors, delivering nanoparticles across the blood-brain tumor barrier presents a major challenge. Dual mode magnetic resonance imaging and fluorescent imaging probes have been developed where relaxation based Gd-DOTA or ParaCEST agents and a Near-Infrared (NIR) fluorescent dye, DL680 were conjugated on the surface of dendrimer. The and imaging of the dual-modality contrast agent showed excellent potential utility for identifying the location of glioma tumors.

Glioblastoma: Targeting Angiogenesis and Tyrosine Kinase Pathways.

Angiogenesis is a hallmark of glioblastoma (GBM) and remains an important therapeutic target in its treatment, especially for recurrent GBM. GBMs are characterized by the release of vascular endothelial growth factor (VEGF), an important regulator and promoter of angiogenesis. Therefore, antiangiogenic therapies (AATs) targeting VEGF or VEGF receptors (VEGFRs) were designed and thought to be an effective tool for controlling the growth of GBM.

Enhancing the Performance of Dye Sensitized Solar Cells Using Silver Nanoparticles Modified Photoanode.

In this study, silver nanoparticles were synthesized, characterized, and applied to a dye-sensitized solar cell (DSSC) to enhance the efficiency of solar cells. The synthesized silver nanoparticles were characterized with UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, and field emission scanning electron microscopy. The silver nanoparticles infused titanium dioxide film was also characterized by Fourier transform infrared and Raman spectroscopy.

MiR-17-92 enriched exosomes derived from multipotent mesenchymal stromal cells enhance axon-myelin remodeling and motor electrophysiological recovery after stroke.

MiR-17-92 cluster enriched exosomes derived from multipotent mesenchymal stromal cells (MSCs) increase functional recovery after stroke. Here, we investigate the mechanisms underlying this recovery. At 24 h (h) post transient middle cerebral artery occlusion, rats received control liposomes or exosomes derived from MSCs infected with pre-miR-17-92 expression lentivirus (Exo-miR-17-92) or control lentivirus (Exo-Con) intravenously.

Photophysical Studies of Ruthenium-Based Complexes and the Performance of Nanostructured TiO Based Dye Sensitized Solar Cells.

Dye-sensitized solar cells (DSSCs) have attracted enormous attention in the last couple of decades due to their relatively small size, low cost and minimal environmental impact. DSSCs convert solar energy to electrical energy with the aid of a sensitizing dye. In this work, two ruthenium-based dyes, tris(bipyridine)ruthenium(II) chloride (Rubpy) and ruthenium(II)2,2'-bis(benzimidazol-2-yl)-4,4'-bipyridine (RubbbpyH), were synthesized, characterized, and investigated for use as dye sensitizers in the fabrication of DSSCs.

Lipoic Acid Decorated Gold Nanoparticles and Their Application in the Detection of Lead Ions.

A simple colorimetric method has been developed for the detection of lead (Pb) in water samples using lipoic acid-functionalized gold nanoparticles. The lipoic acid-functionalized gold nanoparticles are induced to aggregate in the presence of the Pb which results in a change in the color of the functionalized gold nanoparticles. The change in color and the amount of Pb producing the change could be monitored via UV-visible spectrophotometry.

Terahertz Reflectometry Imaging of Carbon Nanomaterials for Biological Application.

The multiwalled carbon nanotubes has a myriad of applications due to its unique electrical and mechanical properties. The biomedical application of multiwalled carbon nanotubes that have been reported include drug delivery, medical imaging, gene delivery, tissue regeneration, and diagnostics. Proper characterization is required to enhance the potential application of the multiwalled carbon nanotubes.

MRI Monitoring of Cerebral Blood Flow after the Delivery of Nanocombretastatin across the Blood Brain Tumor Barrier.

Introduction of polymeric nanoparticles in cancer therapeutics is widely investigated since nanomedicine often enables the intratumoral delivery of drugs with increased efficacy with minimal side effects. In this study MRI monitoring was employed to study the therapeutic effect of nanocombretastatin (G3-CA4) in an orthotopic glioma model. Water insoluble combretastatin (CA4) was conjugated to a small-sized water soluble G3-succinamic acid PAMAM dendrimer.

Dendrimer-based Nanoparticle for Dye Sensitized Solar Cells with Improved Efficiency.

Dye sensitized solar cells were fabricated with DyLight680 (DL680) dye and its corresponding europium conjugated dendrimer, DL680-Eu-G5PAMAM, to study the effect of europium on the current and voltage characteristics of the DL680 dye sensitized solar cell. The dye samples were characterized by using Absorption Spectroscopy, Emission Spectroscopy, Fluorescence lifetime and Fourier Transform Infrared measurements. Transmission electron microscopy imaging was carried out on the DL680-Eu-G5PAMAM dye and DL680-Eu-G5PAMAM dye sensitized titanium dioxide nanoparticles to analyze the size of the dye molecules and examine the interaction of the dye with titanium dioxide nanoparticles.

Fluorinated Eu-based multimodal contrast agent for temperature- and redox-responsive magnetic resonance imaging.

Magnetic resonance imaging (MRI) using redox-active, Eu-containing complexes is one of the most promising techniques for noninvasively imaging hypoxia . In this technique, positive (-weighted) contrast enhancement persists in areas of relatively low oxidizing ability, such as hypoxic tissue. Herein, we describe a fluorinated, Eu-containing complex in which the redox-active metal is caged by intramolecular interactions.

Application of Dendrimer-based Nanoparticles in Glioma Imaging.

Dendritic polymers or dendrimers present an alternate template for the development of nanoparticulate-based drug delivery and imaging systems. The smaller size (~7-12 nm) of dendrimers have the advantage over the other particles, because its smaller size can possibly improve tumor penetration and the inclusion of tumor specific drug release mechanisms. A Paramagnetic Chemical Exchange Saturation Transfer (PARACEST) MRI contrast agent, Eu-DOTA-Gly4 or a clinical relevant Gd-DOTA was conjugated on the surface of a G5 PAMAM dendrimer.

Temozolomide arrests glioma growth and normalizes intratumoral extracellular pH.

Gliomas maintain an acidic extracellular pH (pH), which promotes tumor growth and builds resistance to therapy. Given evidence that acidic pH beyond the tumor core indicates infiltration, we hypothesized that imaging the intratumoral pH in relation to the peritumoral pH can provide a novel readout of therapeutic influence on the tumor microenvironment. We used Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), which utilizes chemical shifts of non-exchangeable protons from macrocyclic chelates (e.

MicroRNA cluster miR-17-92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats.

Background And Purpose: Multipotent mesenchymal stromal cell (MSC) harvested exosomes are hypothesized as the major paracrine effectors of MSCs. In vitro, the miR-17-92 cluster promotes oligodendrogenesis, neurogenesis, and axonal outgrowth. We, therefore, investigated whether the miR-17-92 cluster-enriched exosomes harvested from MSCs transfected with an miR-17-92 cluster plasmid enhance neurological recovery compared with control MSC-derived exosomes.

Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models.

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM.

pH-Dependent Cellular Internalization of Paramagnetic Nanoparticle.

A hallmark of the tumor microenvironment in malignant tumor is extracellular acidosis, which can be exploited for targeted delivery of drugs and imaging agents. A pH sensitive paramagnetic nanoaparticle (NP) is developed by incorporating GdDOTA-4AmP MRI contrast agent and pHLIP (pH Low Insertion Peptide) into the surface of a G5-PAMAM dendrimer. pHLIP showed pH-selective insertion and folding into cell membranes, but only in acidic conditions.

Targeting Triple Negative Breast Cancer with a Small-sized Paramagnetic Nanoparticle.

There is no available targeted therapy or imaging agent for triple negative breast cancer (TNBC). We developed a small-sized dendrimer-based nanoparticle containing a clinical relevant MRI contrast agent, GdDOTA and a NIR fluorescent dye, DL680. Systemic delivery of dual-modal nanoparticles led to accumulation of the agents in a flank mouse model of TNBC that were detected by both optical and MR imaging.

Targeting Glioma with a Dual Mode Optical and Paramagnetic Nanoprobe across the Blood-brain Tumor Barrier.

In brain tumors, delivering nanoparticles across the blood-tumor barrier presents major hurdles. A clinically relevant MRI contrast agent, GdDOTA and a near-infrared (NIR) fluorescent dye, DL680 were conjugated to a G5 PAMAM dendrimer, thus producing a dual-mode MRI and NIR imaging agent. Systemic delivery of the subsequent nano-sized agent demonstrated glioma-specific accumulation, probably due to the enhanced permeability and retention effect.

Myelin-targeted, texaphyrin-based multimodal imaging agent for magnetic resonance and optical imaging.

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results.