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The immunosuppressive microenvironment of solid tumours reduces the antitumour activity of chimeric antigen receptor T cells (CAR-T cells). Here, we show that the release-through the implantation of a hyaluronic acid hydrogel-of CAR-T cells targeting the human chondroitin sulfate proteoglycan 4, polymer nanoparticles encapsulating the cytokine interleukin-15 and platelets conjugated with the checkpoint inhibitor programmed death-ligand 1 into the tumour cavity of mice with a resected subcutaneous melanoma tumour inhibits the local recurrence of the tumour as well as the growth of distant tumours, through the abscopal effect. The hydrogel, which functions as a reservoir, facilitates the enhanced distribution of the CAR-T cells within the surgical bed, and the inflammatory microenvironment triggers platelet activation and the subsequent release of platelet-derived microparticles. The post-surgery local delivery of combination immunotherapy through a biocompatible hydrogel reservoir could represent a translational route for preventing the recurrence of cancers with resectable tumours.

Chimeric antigen receptor T cell (CAR T) therapy was a milestone in the treatment of relapsed and refractory B cell malignancies. However, beneficial effects of CAR T cells have not been obtained in solid tumors yet. Herein, we implement a porous microneedle patch that accommodates CAR T cells and allows in situ penetration-mediated seeding of CAR T cells when implanted in the tumor bed or in the post-surgical resection cavity. CAR T cells loaded in the pores of the microneedle tips were readily escorted to the tumor in an evenly scattered manner without losing their activity. Such microneedle-mediated local delivery enhanced infiltration and immunostimulation of CAR T cells as compared to direct intratumoral injection. This tailorable patch offers a transformative platform for scattered seeding of living cells for treating a variety of tumors.

Blood tests are a vital source of information for disease diagnosis and monitoring. Blood sample contamination due to hemolysis (the rupturing of red blood cells) is a significant problem that can result in incorrect diagnoses, delayed treatment, and inappropriate prescriptions. Therefore, a simple, rapid test is needed to detect the occurrence of hemolysis. Here we propose a new miniature spectroscopic device, integrated onto an optical fiber platform, which can quickly and reliably determine the amount of free hemoglobin in a small droplet of blood plasma. Optimal design parameters for the device were first calculated theoretically, and then the device was fabricated and tested. Experimental tests demonstrated that the device can quickly measure free plasma hemoglobin over a wide range of concentration (0–500 mg/dL) and with a low detection limit (

Nanoscale metal composite materials with tunable properties have attracted interest in many areas, such as catalysis, electronics, and photography. Typical matrices include zeolites, metal oxides, or polymer films. This study reports for first time the incorporation of a dinuclear copper (II) complex in polyethylene oxide (PEO) fiber mat by electrospinning. EPR studies have shown that the complex remained intact and stable within the polymer fibers. The fiber morphology was characterized by SEM. The absorption of the complex allowed to monitor the composition and distribution of the metal on the material.

Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (AβCs) with a multicompartmental 'vesicles-in-vesicle' superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the AβCs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (

We developed an antigen delivery system based on the nanoerythrocyte vehicle combined with anti–PD-L1 for cancer immunotherapy., Erythrocytes or red blood cells (RBCs) represent a promising cell-mediated drug delivery platform due to their inherent biocompatibility. Here, we developed an antigen delivery system based on the nanoerythrosomes derived from RBCs, inspired by the splenic antigen-presenting cell targeting capacity of senescent RBCs. Tumor antigens were loaded onto the nanoerythrosomes by fusing tumor cell membrane–associated antigens with nanoerythrosomes. This tumor antigen–loaded nanoerythrosomes (nano-Ag@erythrosome) elicited antigen responses in vivo and, in combination with the anti–programmed death ligand 1 (PD-L1) blockade, inhibited the tumor growth in B16F10 and 4T1 tumor models. We also generated a tumor model showing that “personalized nano-Ag@erythrosomes” could be achieved by fusing RBCs and surgically removed tumors, which effectively reduced tumor recurrence and metastasis after surgery.

This study demonstrates the potential of porphyrin modified antimicrobial peptides for indication of bacterial targets on the basis of changes in the spectrophotometric characteristics of the construct. Detection is a result of changes in the structure of the antimicrobial peptide upon target binding. Those constructs comprised of peptides that offer little or no change in conformation upon interaction with bacterial cells demonstrated negligible changes in absorbance and fluorescence when challenged using Escherichia coli or Bacillus cereus. CD analysis confirms the presence/absence of conformational changes in the porphyrin-peptide constructs. Differing spectrophotometric responses were observed for constructs utilizing different peptides. The incorporation of metals into the porphyrin component of the constructs was shown to alter their spectrophotometric characteristics as well as the resulting absorbance and fluorescence changes noted upon interaction with a target. The described constructs offer the potential to enable a new type of biosensing approach in which the porphyrin-peptide indicators offer both target recognition and optical transduction, requiring no additional reagents. Keywords: Antimicrobial peptide, Porphyrin, Bacterial detection, Absorbance, Fluorescence

Aniline-peptide (FLDQV, FLDQVC, Dansyl-FLDQV, Dansyl-FLDQVC, and FLDQV-AMC) mixtures underwent oxidative chemical and electrochemical polymerization in excess of aniline. The products of the chemical polymerization were low molecular weight polymers containing more than 70% peptide. Electrochemically polymerized species polyaniline-FLDQV (PANI-FLDQV) consisted mainly of polyaniline units containing about 10% peptide. The solubility of the latter in 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) was similar to the camphorsulfonic acid (CSA) doped emeraldine base (PANI-CSA) solubility, however the weight composition of the electrospun fibers produced from the two polymers was significantly different. 2D 1H-13C HSQC analyses were employed to analyze the binding between the aniline and peptide moieties. Binding of peptide to polyaniline is reflected by the appearance of extra cross-peaks which display line broadening between the free polyaniline and the free pentapeptide. Peptides may be chemically bonded to the polymer molecules, but they may also act as doping agents to the nitrogen atoms via hydrogen bonding.

Hydrogen peroxide (H

The phenol photocatalytic degradation was investigated using heterogeneous catalyst Ag-doped ZnO nanowires under UV irradiation. Ag-ZnO nanowires were immobilized on borosilicate glass via a simple hydrothermal technique. Preliminary photodegradation studies were performed with Ag-ZnO nanowires at various concentrations of phenol (10 - 60 mg/L) at undiluted pH. After determination of the optimal initial concentration (30 mg/L), additional parameters including pH and light intensity were investigated to optimize photodegradation of phenol for large-scale application. The experimental results illustrate that the kinetics of degradation of phenol are pseudo-first order. Based on the relationship, experimental model and empirical correlation were generated and compared for validity. The experimental data were found to fit a cubic model (linear in UV irradiation intensity, I, and cubic in pH), over ranges of 10 - 60 W (UV lamp power) and 2.7 - 11.0 (pH) with a coefficient of determination (R2) of 0.9934. This model, of the form K(I, pH) = c00 + c10I + c01pH + c11IpH + c02pH2 + c12IpH2 + c03pH3 was found to yield a better fit than simpler (quadratic) or more complex (quartic) polynomial-based models considered. The model parameters cij and corresponding 95% confidence intervals were obtained.

We propose a new approach to the modular packaging of microfluidic components, in which different functional components are not only fabricated separately but are also designed to be individually removable for the purposes of replacement or subsequent analysis. In this paper, we demonstrate one such component: a stand-alone microfluidic filter that can be custom-fabricated and then connected, disconnected, and replaced on a microfluidic chip as needed. This filter is also designed such that particles captured on the filter can be further analyzed or processed directly on the filter itself—for example, for microscopic examination or cell culturing. The filter is a thin (1 μm) transparent silicon nitride membrane that can be designed and fabricated according to specifications for different applications. This material is suitable for microscale fabrication; filtration of a variety of solutions, including biological samples; and subsequent particle imaging and processing. The porous nature of the thin filter allows for particle separation under relatively low pressures, thus protecting the particles from rupture or membrane damage. We describe two methods for integrating the filter apparatus onto a microfluidic chip such that it can be inserted, removed, and replaced. To demonstrate the utility of this approach, we fabricated custom-designed silicon-based filters, incorporated them onto microfluidic systems then filtered microparticles and live cells from test solutions, and finally removed the filters to image the microparticles and culture the cells directly on the filter membranes.

Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are pregnancy-related complications with high rates of morbidity and mortality. HELLP syndrome, in particular, can be difficult to diagnose. Recent work suggests that elevated levels of free cell hemoglobin in blood plasma can, as early as the first trimester, potentially serve as a diagnostic biomarker for impending complications. We therefore developed a point-of-care mobile phone–based platform that can quickly characterize a patient's level of hemolysis by measuring the color of blood plasma. The custom hardware and software are designed to be easy to use. A sample of the whole blood (~10 µL or less) is first collected into a clear capillary tube or microtube, which is then inserted into a low-cost 3D-printed sample holder attached to the phone. A 5–10 min period of quiescence allows for gravitational sedimentation of the red blood cells, leaving a layer of yellowish plasma at the top of the tube. The phone camera then photographs the capillary tube and analyzes the color components of the cell-free plasma layer. The software converts these color values to a concentration of free hemoglobin, based on a built-in calibration curve, and reports the patient's hemolysis level: non-hemolyzed, slightly hemolyzed, mildly hemolyzed, frankly hemolyzed, or grossly hemolyzed.. The accuracy of the method is ~1 mg dL−1. This phone-based point-of-care system provides the potentially life-saving advantage of a turnaround time of about 10 min (versus 4+hours for conventional laboratory analytical methods) and a cost of approximately one dollar USD (assuming you have the phone and the software are already available).

Polyaniline in form of emeraldine salt and emeraldine base was used as a matrix to attach several labeled and non-labeled dioxin selective pentapeptides both directly to the polymer and using glutaraldehyde as a linker. The peptides have been selected as a model to study the binding process due to their smaller size, lower sensitivity to the environment and potential application as solid state extraction reagents for chlorinated toxins. The composition and the properties of the compounds were investigated by means of elemental analysis, XPS, FTIR, UV/vis, and fluorescence spectroscopy. The results have shown that 3.30-7.76% peptides were attached to the emeraldine base both with and without a linker. Glutaraldehyde and the peptides were connected to the matrix via chemical bond resulting in formation of compounds whit similar composition and stability in a broad pH range. The influence of the linker and the peptides on the electronic properties and composition of the polymer have been investigated by principal component analysis.

Hydrogen peroxide (H2 O2 )-responsive materials have been employed as drug delivery or diagnostic systems to treat or detect diseases with abnormal oxidative stress. A number of H2 O2 -responsive systems have been developed, and they have achieved great progress in controlled drug delivery for disease treatment. However, pathological sites with elevated H2 O2 level, such as cancer and inflammation, have their own characteristics; therefore the material structures and the subsequent formulations should be reasonably designed to acquire maximized therapeutic effects. In this progress report, we overview the development of H2 O2 -responsive functional groups for constructing H2 O2 -responsive formulations, as well as the guidance for designing suitable formulations to treat each specific pathological condition. The challenges and perspectives in this field are also discussed.

Three novel aza-crown ether derivatives incorporating 4-amino-7-nitrobenzaoxa-1,3-diazole (NBD) chromophore were synthesized and their structure confirmed by (1)H-NMR, IR and elemental analysis. The influence of the solvent polarity and protonation on the photophysical properties of NBD-15-crown-5 was studied by UV/Vis and fluorescence methods. The influence of the investigated cations on the absorption spectra of the ligands was negligible, however emission was strongly affected. Complexation and binding stability of NBD-aza-15-crown-5 and NBD-aza-18-crown-6 were studied using fluorescence spectroscopy. NBD-aza-18-crown-6 exhibits strong selectivity toward Ca(2+) and Sr(2+) ions with formation constants about 10(3) times higher than the formation constants with the other ions included in the study.

The present study investigates the binding properties of four dansyl substituted aza-crown ethers with alkali, alkaline earth metal ions and ammonium. The influence of the solvent polarity and protonation on the photophysical properties of the compounds was studied by UV/Vis and fluorescence methods. The host species caused only slight changes on the absorption spectra of the ligands. The fluorescence changes were more pronounced and concentration dependent thus allowing to calculate the binding constants of the process. The most stable complex under our working conditions was the one between Ba(2+) and DNS18C6.