Comparison of dose selection based on target engagement versus inhibition of receptor-ligand interaction for checkpoint inhibitors.

Immune checkpoint inhibitors block the interaction between a receptor on one cell and its ligand on another cell, thus preventing the transduction of an immunosuppressive signal. While inhibition of the receptor-ligand interaction is key to the pharmacological activity of these drugs, it can be technically challenging to measure these intercellular interactions directly. Instead, target engagement (or receptor occupancy) is commonly measured, but may not always be an accurate predictor of receptor-ligand inhibition, and can be misleading when used to inform clinical dose projections for this class of drugs.

Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade.

DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia.

Quantifying the efficacy of checkpoint inhibitors on CD8 cytotoxic T cells for immunotherapeutic applications via single-cell interaction.

The inhibition of the PD1/PDL1 pathway has led to remarkable clinical success for cancer treatment in some patients. Many, however, exhibit little to no response to this treatment. To increase the efficacy of PD1 inhibition, additional checkpoint inhibitors are being explored as combination therapy options.

Machine learning-aided quantification of antibody-based cancer immunotherapy by natural killer cells in microfluidic droplets.

Natural killer (NK) cells have emerged as an effective alternative option to T cell-based immunotherapies, particularly against liquid (hematologic) tumors. However, the effectiveness of NK cell therapy has been less than optimal for solid tumors, partly due to the heterogeneity in target interaction leading to variable anti-tumor cytotoxicity. This paper describes a microfluidic droplet-based cytotoxicity assay for quantitative comparison of immunotherapeutic NK-92 cell interaction with various types of target cells.

Interaction kinetics with transcriptomic and secretory responses of CD19-CAR natural killer-cell therapy in CD20 resistant non-hodgkin lymphoma.

We investigated the cytolytic and mechanistic activity of anti-CD19 chimeric antigen receptor natural killer (CD19.CAR.NK92) therapy in lymphoma cell lines (diffuse large B-cell, follicular, and Burkitt lymphoma), including rituximab- and obinutuzumab-resistant cells, patient-derived cells, and a human xenograft model.

Photosensitizer Tailored Surface Functionalized Carbon Dots for Visible Light Induced Targeted Cancer Therapy.

Herein, a photosensitizer (riboflavin) tailored surface functionalized carbon dot () was designed to utilize it in visible light induced targeted cancer therapy. At first, phenylboronic acid appended biotinylated blue emitting carbon dot () was synthesized. Riboflavin having "diol" moiety was covalently linked with this to prepare by using complementary boronate-diol linkage.

Anti-myeloma activity and molecular logic operation by Natural Killer cells in microfluidic droplets.

Immune-targeted therapies that activate effector lymphocytes such as Natural Killer (NK) cells are currently being investigated for the treatment of Multiple myeloma (MM), the second most common form of hematological cancer. However, individual NK cells are highly heterogeneous in their cytolytic potential, making it difficult to detect, quantify and correlate the outcome of dynamic effector-target cell interactions at single cell resolution. Here, we present a microfluidic bioassay platform capable of activity-based screening of cellular and molecular immunotherapies.

Ultrafast Parallelized Microfluidic Platform for Antimicrobial Susceptibility Testing of Gram Positive and Negative Bacteria.

Antimicrobial susceptibility testing (AST) is an essential diagnostic procedure to determine the correct course of treatment for various types of pathogen infections. Patients are treated with broad spectrum antibiotics until AST results become available, which has contributed to the emergence of multidrug resistant bacteria worldwide. Conventional AST methods require 16-24 h to assess sensitivity of the bacteria to a given drug and establish its minimum inhibitory concentration (MIC).

Microstructure characterization of biocompatible heterojunction hydrogen titanate-AgO nanocomposites for superior visible light photocatalysis and antibacterial activity.

Hydrogen trititanate (HTiO·2HO) and hydrogen trititanate/AgO hybrid nanocomposites (NCs) with novel structure have been synthesized by a simple solvothermal route followed by Na/H ion-exchange. Growths of hydrogen trititanate with nanofiber (HTNF) and nanotube (HTNT) morphologies and hydrogen trititanate-AgO (HTFAG and HTTAG) nanocomposites have been tailored by controlling the solvent media. Detailed microstructure characterization of all these samples have been carried out by Rietveld refinement of XRD data and analyzing FESEM/HRTEM micrographs and FTIR spectra.

Self-assembly of surface functionalized amphiphilic carbon dots: tuning in morphological manifestations.

Despite the continuous surge of interest in supramolecular chemistry, the design and synthesis of building blocks to develop diverse examples of self-assemblies is still challenging. During the past decades, formation of self-assemblies such as micelles, vesicles, and gels with a fibril network using amphiphiles has been investigated at length. Considering the increasing applications of these self-aggregates across the scientific domain, it is crucial to adopt an alternative strategy for the preparation of self-aggregates using a new building block that has been applied in diverse domains.

Microfluidic assembly of hydrogel-based immunogenic tumor spheroids for evaluation of anticancer therapies and biomarker release.

Diffuse large B cell lymphoma (DLBCL), the most common subtype of Non-Hodgkin lymphoma, exhibits pathologic heterogeneity and a dynamic immunogenic tumor microenvironment (TME). However, the lack of preclinical in vitro models of DLBCL TME hinders optimal therapeutic screening. This study describes the development of an integrated droplet microfluidics-based platform for high-throughput generation of immunogenic DLBCL spheroids.

Tunable Aggregation-Induced Multicolor Emission of Organic Nanoparticles by Varying the Substituent in Naphthalene Diimide.

In this article, we have designed l-aspartic acid-linked naphthalene diimide (NDI)-based amphiphilic molecules having a benzyl ester group at both the terminals with varying substituents (NAB-1-5). The substituent was judiciously modified from an electron-withdrawing group (EWG) like nitrobenzene to an electron-donating group (EDG), methoxybenzene, and finally to an extended aromatic residue (naphthalene) to regulate the π-electron density at the terminal of NDI derivatives. All of the synthesized NDI derivatives were molecularly dissolved in dimethyl sulfoxide (DMSO), and with an increase in the water content within the DMSO solution, the NDI derivative starts to get self-assembled through J-aggregation at and above 40% water content.

Glucose oxidase mediated targeted cancer-starving therapy by biotinylated self-assembled vesicles.

Herein, we demonstrate glucose oxidase (GOx) mediated targeted cancer-starving therapy by self-assembled vesicle of trimesic acid based biotinylated amphiphile (TMB). The TMB vesicles entrapped GOx and selectively killed cancer cells (HeLa, B16F10), with ∼6-fold higher efficiency compared to non-cancer cells (CHO, NIH3T3), by blocking the energy supply to tumors through the oxidation of intracellular glucose.

Tailor-Made Self-Assemblies from Functionalized Amphiphiles: Diversity and Applications.

The objective of this feature article is to coalesce our recent advancements on different expressions of tailor-made supramolecular self-assemblies and to explore them as a function of molecular architecture. In the last decade, we have developed a library of elegant and simple functional amphiphilic small molecules, which have very interesting abilities to form diverse manifestations of supramolecular self-assemblies such as micelles, reverse micelles, vesicles, fibers, supramolecular gels, and so on. Each of the expressions of the self-aggregated structures has its individual prominence and finds important applications in the fields of chemistry, physics, biology, and others.

Dynamic Analysis of Human Natural Killer Cell Response at Single-Cell Resolution in B-Cell Non-Hodgkin Lymphoma.

Natural killer (NK) cells are phenotypically and functionally diverse lymphocytes that recognize and kill cancer cells. The susceptibility of target cancer cells to NK cell-mediated cytotoxicity depends on the strength and balance of regulatory (activating/inhibitory) ligands expressed on target cell surface. We performed gene expression arrays to determine patterns of NK cell ligands associated with B-cell non-Hodgkin lymphoma (b-NHL).

Self-Assembled Vesicle-Carbon Nanotube Conjugate Formation through a Boronate-Diol Covalent Linkage.

A vesicle-single walled carbon nanotube (CNT) conjugate was developed by a boronic acid-diol covalent linkage between a self-assembled vesicle and dispersed CNT. Trimesic acid based phenylboronic acid appended triple-tailed amphiphiles (T1 and T1S) were synthesized that formed monolayered vesicles through H-aggregation in DMSO-water (2:1 v/v) and pure water, respectively. Aqueous CNT dispersion was prepared with cholesterol-based glucose-functionalized amphiphile (D1).

Quantification of intercellular adhesion forces measured by fluid force microscopy.

The mechanics of cancer cell adhesion to its neighboring cells, homotypic or heterotypic, have significant impact on tumor progression and metastasis. Intercellular adhesion has been quantified previously using atomic force microscopy-based methods. Here we show the feasibility of the recently developed fluidic force microscopy (FluidFM) to measure adhesive forces exerted by breast cancer cells.

Equivalent Resistance from the Quantum to the Classical Transport Limit.

We generalize the concept of equivalent resistance to the entire range from coherent quantum to diffusive classical transport by introducing the notion of transport equivalent networks. We show that this novel concept presents us with a platform to simplify the structure of quantum networks while preserving their global and local transport properties, even in the presence of electron-phonon or electron-electron interactions. This allows us to describe the evolution of equivalent quantum networks to equivalent classical resistor networks with increasing interaction strength.

A droplet-merging platform for comparative functional analysis of m1 and m2 macrophages in response to e. coli-induced stimuli.

Microfluidic droplets are used to isolate cell pairs and prevent crosstalk with neighboring cells, while permitting free motility and interaction within the confined space. Dynamic analysis of cellular heterogeneity in droplets has provided insights in various biological processes. Droplet manipulation methods such as fusion and fission make it possible to precisely regulate the localized environment of a cell in a droplet and deliver reagents as required.

Isothermal Amplification Strategies for Detection in Microfluidic Devices.

Isothermal rolling circle amplification (RCA) is used to detect nucleic and non-nucleic acid biomarkers with high sensitivity. Immuno-RCA, the specific detection of proteins via antigen-antibody recognition, has been miniaturized for microfluidic platforms to reduce reagent and sample consumption, accelerate reaction kinetics, and enhance the sensitivity and specificity of detection.

Fluorescent Indicator Displacement Assay: Ultrasensitive Detection of Glutathione and Selective Cancer Cell Imaging.

This Research Article reports the development of nanohybrid comprising of anionic carbon dots (ACD) protected gold nanoparticle (GNP). ACD directly cap GNP through its anionic surface functionalization leading to the formation of stable aqueous GNP dispersion. This newly developed ACD-GNP nanohybrid has been thoroughly characterized by different spectroscopic and microscopic techniques.

Hydrophobically Tailored Carbon Dots toward Modulating Microstructure of Reverse Micelle and Amplification of Lipase Catalytic Response.

This article delineates the modulation of microstructure of cationic reverse micelle utilizing hydrophobically modified carbon dots (CDs) with varying surface functionalizations. Citric acid was used as the source of the carbon core, and Na-salt of glycine, glycine, Na-salt of 11-aminoundecanoic acid, 11-aminoundecanoic acid, and n-hexadecylamine were used for the surface fabrication of CDs to produce CD 1s, CD 1a, CD 2s, CD 2a, and CD 3, respectively. All these CDs having dimension of 5-7 nm were characterized by spectroscopic and microscopic techniques.

Innovative Tools and Technology for Analysis of Single Cells and Cell-Cell Interaction.

Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities.

T Cell Dynamic Activation and Functional Analysis in Nanoliter Droplet Microarray.

Objective: Characterization of the heterogeneity in immune reactions requires assessing dynamic single cell responses as well as interactions between the various immune cell subsets. Maturation and activation of effector cells is regulated by cell contact-dependent and soluble factor-mediated paracrine signalling. Currently there are few methods available that allow dynamic investigation of both processes simultaneously without physically constraining non-adherent cells and eliminating crosstalk from neighboring cell pairs.

Spatially-resolved intracellular sensing of hydrogen peroxide in living cells.

Understanding intracellular redox chemistry requires new tools for the site-specific visualization of intracellular oxidation. We have developed a spatially-resolved intracellular sensor of hydrogen peroxide, HyPer-Tau, for time-resolved imaging in live cells. This sensor consists of a hydrogen peroxide-sensing protein tethered to microtubules.