A Molecular Thermodynamic Model of Complexation in Mixtures of Oppositely Charged Polyelectrolytes with Explicit Account of Charge Association/Dissociation

Into an extended Voorn–Overbeek (EVO) free energy model of polyelectrolyte (PE) complexation and phase behavior, we incorporate three classes of short-ranged electrostatic effects, namely counterion association–dissociation, cross-chain ion pairing (IP), and charge regulation by treating each as a reversible chemical reaction leading to a corresponding law of mass action in a self-consistent fashion. The importance of each reaction is controlled by a corresponding chemistry-dependent standard free energy input parameter. Our model also accounts for Born (or ion solvation) energy using a linear mixing rule for the effective dielectric constant. In monophasic systems, the proposed model can qualitatively explain the observed shifts in acidity and basicity observed in potentiometric titration of weak PEs in the presence of salt and oppositely charged PEs in accordance with Le Châtelier’s principle. We demonstrate how a competition between counterion condensation (CC) and IP alone can explain the complex coacervation of strongly charged PEs as well as the existence of a critical salt concentration. Binodal diagrams predicted in our model are also affected by long-ranged electrostatics and are most sensitive to IP strength both for weak and strong PEs. The extent of IP increases in the dense phase at the expense of reduced CC upon coacervation consistent with counter release view of complex coacervation. We compare binodal diagrams predicted by our model against experimental data for both weakly and strongly dissociating polyions pairs and find a plausible parameter set that leads to an acceptable and partial agreement with experiments in the two cases, respectively

Relationship between Polyelectrolyte Bulk Complexation and Kinetics of Their Layer-by-Layer Assembly

The effects of pH and salinity on both the bulk phase behavior and the layer-by-layer (LbL) growth kinetics are investigated for polyanion poly­(acrylic acid) or PAA with two polycations, namely poly­(<i>N</i>,<i>N</i>-dimethylaminoethyl methacrylate) or PDMAEMA and poly­(diallyldimethylammonium chloride) or PDADMAC, with the goal of relating the phase behavior to the LbL growth kinetics. Depending on salinity, pH, and mixing ratio, the complex formed in the bulk is either a powdery precipitate or a gel-like coacervate, and the multilayers grow either linearly or exponentially with deposition time. In addition to primary Coulombic interactions, we observe that polymer-specific interactions have a profound effect on both bulk complexation and LbL growth of the three PE pairs studied here. The overall strength of interaction between polyelectrolytes, as indicated by their phase behavior, has a nonmonotonic effect on LbL growth rate, apparently because stronger interactions not only increase the driving force for diffusion but also reduce the effective diffusion coefficient of a polyelectrolyte molecule through the LbL multilayer. As a result, there is little correspondence between coacervation and exponential growth on one hand and precipitation and linear growth on the other. Salt concentration has a nonmonotonic effect on LbL growth kinetics at pH 7, with exponential growth found over the range 15–60% of the critical salt concentration (<i>C</i>_S^c) needed to transition from coacervation to a clear solution in the bulk, regardless of the physical chemistry of polyelectrolytes employed, whereas salt concentrations both below and above this range result in linearly growing films. Finally, for our polyelectrolyte pairs at pH 7, we report a “universal curve” for the dependence of LbL growth rate, normalized by its maximum value, against the salt concentration, normalized by <i>C</i>_S^c. If it proves to be robust, this correlation could be used to estimate optimal salinity for LbL growth from bulk measurements of the critical salt concentration needed to suppress complexation

Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies

AbstractAdvancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years

Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies

AbstractAdvancements in adoptive cell therapy over the last four decades have revealed various new therapeutic strategies, such as chimeric antigen receptors (CARs), which are dedicated immune cells that are engineered and administered to eliminate cancer cells. In this context, CAR T-cells have shown significant promise in the treatment of hematological malignancies. However, many obstacles limit the efficacy of CAR T-cell therapy in both solid tumors and hematological malignancies. Consequently, CAR-NK and CAR-M cell therapies have recently emerged as novel therapeutic options for addressing the challenges associated with CAR T-cell therapies. Currently, many CAR immune cell trials are underway in various human malignancies around the world to improve antitumor activity and reduce the toxicity of CAR immune cell therapy. This review will describe the comprehensive literature of recent findings on CAR immune cell therapy in a wide range of human malignancies, as well as the challenges that have emerged in recent years