Attractive Gel Research Articles

Attractive Pickering emulsion gel loaded with oxaliplatin and lactate dehydrogenase inhibitor increases the anti-tumor effect in hepatocellular carcinoma

Attractive Pickering emulsion gel loaded with oxaliplatin and lactate dehydrogenase inhibitor increases the anti-tumor effect in hepatocellular carcinoma

Effects of Attractive Pickering emulsion gels loaded with oxaliplatin and lactate dehydrogenase inhibitors in hepatocellular carcinoma.

e16235 Background: Oxaliplatin (OXA) can be used as a palliative treatment for advanced hepatocellular carcinoma (HCC). While most patients still have rapid disease progression after OXA due to the drug resistance. The lactate dehydrogenase A (LDHA) inhibitors can reduce the inflammation-induced effects, metastasis, and proliferation potential of cancer cells. The combination of OXA and LDHA inhibitor may be an effective treatment for HCC. Methods: We adopt the water-in-oil attractive Pickering emulsion gel (APEG) to deliver OXA and LDHA inhibitor, GSK2837808A (GSK). OXA is dissolved in water and GSK is dissolved in iodized oil. We injected OXA+GSK@gel into the peritumoral tissues of subcutaneously tumorigenic HCC model mice, then observe the tumor size. Next, we apply immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay on the dissected tumors to explore the cell proliferation and apoptosis. Meanwhile, flow analysis on the dissected tumors is applied to investigate the tumor immune microenvironment in HCC. Results: This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly. OXA+GSK@gel has significant anti-tumor effect on HCC model, which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis. Meanwhile, flow analysis confirm that it could activate the tumor immune microenvironment in HCC. The infiltration of CD8+ T cells was increased, thereby providing better anti-tumor effect. Conclusions: The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.

Predicting yielding in attractive colloidal gels.

One of the defining characteristics of soft glassy materials is their ability to exhibit a yield stress, which can result in an overall elasto-visco-plastic mechanics. To design soft materials with specific properties, it is essential to gain a comprehensive understanding of the topological and structural failure points that occur during yielding. However, predicting these failure points, which lead to yielding, is challenging due to the dynamic nature of structure development and its cooccurrence with other complicated processes, such as local rearrangements and anisotropy. In this study, we employ a series of tools from network science to investigate colloidal gels as a model for soft glassy materials during yielding. Our findings reveal that edge betweenness centrality can be utilized as a universal predictor for yielding across various state variables, including the volume fraction of solids, the strength, and the range of attraction between colloids.

Aqueous Laponite® dispersions are attractive gels, not repulsive Wigner glasses: A critical commentary

An aqueous dispersion of Laponite® has been studied in the literature for over the past three decades. Typically, the aqueous dispersion of Laponite® undergoes incessant evolution of its microstructure, wherein its elastic modulus and the mean relaxation time show a continuous increase as a function of time. A considerable amount of discussion has revolved around the nature of this dispersion, specifically whether it can be classified as a repulsive Wigner glass state, characterized by disconnected Laponite® particles stabilized by electrostatic repulsions, or an attractive gel state, in which the particles form a percolated space-spanning network. The proponents of the Wigner glass state also conjecture that this system experiences a glass–glass transition after a period of 2 days has elapsed since its preparation. In this Commentary, we explore this topic from a rheological point of view, analyzing the published literature and performing new experiments. Aided by additional evidence from the literature, we propose that rheological behavior overwhelmingly suggests that an aqueous dispersion of Laponite® undergoes a sol–attractive gel transition and remains in the attractive gel state over at least up to 7 days without undergoing any additional transition. Importantly, rheology, despite being a macroscopic tool governed by principles of mechanics, offers profound insight into the microstructure of this particular system. The corresponding analysis conclusively determines the state of an aqueous dispersion of Laponite® to be an attractive gel.

The effect of thixotropy on the yield transition in reversible, colloidal gels.

Thixotropic yield-stress fluids (TYSFs) are a unique class of materials whose properties are affected by both shear rate and shear history. When sheared, these materials undergo a transition from an elastic solid to a viscoelastic fluid, which is accompanied by a structural transition that slowly recovers upon the cessation of shear. The strong interdependence between structure, dynamics, and rheological properties in TYSFs make it challenging to identify the fundamental physics controlling these phenomena. In this study, we vary the ionic strength of a suspension of cellulose nanocrystals (CNC) to generate model TYSFs with tunable moduli and thixotropic kinetics. We use a novel rheological protocol-serial creep divergence-to identify the physics underlying the yield transition and recovery of CNC gels. Our protocol identifies a critical transition that bifurcates the solid-like and fluid-like regimes of the gels to precisely determine the yield stress of these materials even in the presence of thixotropic effects. Additionally, the thixotropic kinetics collapse onto a single master curve, which we fit to a transient solution to a coupled diffusion-aggregation model. Our work thereby identifies the underlying physicochemical mechanisms driving yielding and thixotropic recovery in attractive colloidal gels.

Induction of Tumor Ferroptosis-Dependent Immunity via an Injectable Attractive Pickering Emulsion Gel.

The combination of ferroptosis inducers and immune checkpoint blockade (ICB) can enhance antitumor effects. However, the efficacy in tumors with low immunogenicity requires further investigation. Herein, we have developed a water-in-oil Pickering emulsion gel to deliver (1S, 3R)-RSL-3 (RSL-3), a ferroptosis inducer dissolved in iodized oil and programmed death-1 (PD-1) antibody, the most commonly used immune checkpoint inhibitor dissolved in water, with optimal characteristics (RSL-3+PD-1@gel). Tumor lipase degrades the continuous oil phase, which results in the slow release of RSL-3 and PD-1 antibody and a notable antitumor effect against low-immunogenic hepatocellular carcinoma (HCC) and pancreatic cancer. Intriguingly, the RSL-3+PD-1@gel induces ferroptosis of tumor cells, resulting in antitumor immune response via accumulation of helper T lymphocyte cells and cytotoxic T cells. Additionally, the single cell sequence profiling analysis during tumor treatment reveals the induction of ferroptosis in tumor cells together with strong antitumor immune response in ascites. This article is protected by copyright. All rights reserved.

Complex optical transport, dynamics, and rheology of intermediately attractive emulsions

Introducing short-range attractions in Brownian systems of monodisperse colloidal spheres can substantially impact their structures and consequently their optical transport and rheological properties. Here, for size-fractionated colloidal emulsions, we show that imposing an intermediate strength of attraction, well above but not much larger than thermal energy (approx 5.6k_{textrm{B}}T), through micellar depletion leads to a striking notch in the measured inverse mean free path of optical transport, 1/ell ^*, as a function of droplet volume fraction, phi. This notch, which appears between the hard-sphere glass transition, phi _{textrm{g}}, and maximal random jamming, phi _{textrm{MRJ}}, implies the existence of a greater population of compact dense clusters of droplets, as compared to tenuous networks of droplets in strongly attractive emulsion gels. We extend a prior decorated core-shell network model for strongly attractive colloidal systems to include dense non-percolating clusters that do not contribute to shear rigidity. By constraining this extended model using the measured 1/ell ^*(phi ), we improve and expand the microrheological interpretation of diffusing wave spectroscopy (DWS) experiments made on attractive colloidal systems. Our measurements and modeling demonstrate richness and complexity in optical transport and shear rheological properties of dense, disordered colloidal systems having short-range intermediate attractions between moderately attractive glasses and strongly attractive gels.

Topological origins of yielding in short-ranged weakly attractive colloidal gels.

Yielding of the particulate network in colloidal gels under applied deformation is accompanied by various microstructural changes, including rearrangement, bond rupture, anisotropy, and reformation of secondary structures. While much work has been done to understand the physical underpinnings of yielding in colloidal gels, its topological origins remain poorly understood. Here, employing a series of tools from network science, we characterize the bonds using their orientation and network centrality. We find that bonds with higher centralities in the network are ruptured the most at all applied deformation rates. This suggests that a network analysis of the particulate structure can be used to predict the failure points in colloidal gels a priori.

Structuring colloidal gels via micro-bubble oscillations.

Locally (re)structuring colloidal gels - micron-sized particles forming a connected network with arrested dynamics - can enable precise tuning of the micromechanical and -rheological properties of the system. A recent experimental study [B. Saint-Michel, G. Petekidis, and V. Garbin, Soft Matter, 2022, 18, 2092] showed that local ordering can be rapidly induced by acoustically modulating an embedded microbubble. Here, we perform Brownian dynamics simulations to understand the mechanical effect of an oscillating microbubble on the next-to-bubble structure of the embedding colloidal gel. Our simulations reveal hexagonal-close-packed structures over a range that is comparable to the amplitude of the oscillations. However, we were unable to reproduce the unexpectedly long-ranged modification of the gel structure - dozens of amplitudes - observed in experiment. This suggests including long-ranged effects, such as fluid flow, should be considered in future computational work.

Shear induced tuning and memory effects in colloidal gels of rods and spheres.

Shear history plays an important role in determining the linear and nonlinear rheological response of colloidal gels and can be used for tuning their structure and flow properties. Increasing the colloidal particle aspect ratio lowers the critical volume fraction for gelation due to an increase in the particle excluded volume. Using a combination of rheology and confocal microscopy, we investigate the effect of steady and oscillatory preshear history on the structure and rheology of colloidal gels formed by silica spheres and rods of length L and diameter D (L/D = 10) dispersed in 11 M CsCl solution. We use a non-dimensional Mason number, Mn (=Fvisc./Fattr.), to compare the effect of steady and oscillatory preshear on gel viscoelasticity. We show that after preshearing at intermediate Mn, attractive sphere gel exhibits strengthening, whereas attractive rod gel exhibits weakening. Rheo-imaging of gels of attractive rods shows that at intermediate Mn, oscillatory preshear induces large compact rod clusters in the gel microstructure, compared to steady preshear. Our study highlights the impact of particle shape on gel structuring under flow and viscoelasticity after shear cessation.

A microstructural investigation of an industrial attractive gel at pressure and temperature.

Oil-continuous drilling fluids used in the oil and gas industry are formulated to be pseudoplastic with a relatively weak yield stress. These fluids are required to maintain their properties over wide temperature and pressure ranges yet there are few methods that can sensitively study the inherent structure and mechanical properties in the fluids under such conditions. Here we study a model oil-continuous drilling fluid formulation as a function of both temperature (up to 153 °C) and pressure (up to 1330 bar) with Diffusive Wave Spectroscopy (DWS). The system comprises a colloidal gel network of clay particles and trapped emulsion droplets. As a function of temperature the system undergoes local structural changes reflected in the DWS dynamics which are also consistent with macroscopic rheological measurements. On cycling to high pressure the system exhibits similar structural and dynamic changes with a strong hysteresis. Although multiple scattering in multicomponent non-ergodic samples does not directly yield self diffusion probe dynamics, the use of microrheology analysis here appears to be in good agreement with direct rheological measurements of the sample linear viscoelasticity at ambient pressure. Thus DWS microrheology succesfully probes irreversible changes in the structure and the mechanical response of the drilling fluid formulation under a high pressure cycle.

Interfacial Engineering of Attractive Pickering Emulsion Gel-Templated Porous Materials for Enhanced Solar Vapor Generation

Solar vapor generation is emerging as one of the most important sustainable techniques for harvesting clean water using abundant and green solar energy. The rational design of solar evaporators to realize high solar evaporation performances has become a great challenge. Here, a porous solar evaporator with integrative optimization of photothermal convention, water transport and thermal management is developed using attractive Pickering emulsions gels (APEG) as templated and followed by interfacial engineering on a molecular scale. The APEG-templated porous evaporators (APEG-TPEs) are intrinsically thermal insulation materials with a thermal conductivity = 0.039 W·m−1·K−1. After hydrolysis, t-butyl groups on the inner-surface are transformed to carboxylic acid groups, making the inner-surface hydrophilic and facilitating water transport through the inter-connected pores. The introduction of polypyrrole layer endows the porous materials with a high light absorption of ~97%, which could effectively convert solar irradiation to heat. Due to the versatility of the APEG systems, the composition, compressive modulus, porosity of APEG-TPEs could be well controlled and a high solar evaporation efficiency of 69% with an evaporation rate of 1.1 kg·m−2·h−1 is achieved under simulated solar irradiation. The interface-engineered APEG-TPEs are promising in clean water harvesting and could inspire the future development of solar evaporators.

Glass-liquid and glass-gel transitions of soft-shell particles.

We study the structure and dynamics of colloidal particles with a spherical hard core and a thermo-responsive soft shell over the whole phase diagram by means of small-angle x-ray scattering and x-ray photon correlation spectroscopy. By changing the effective volume fraction by temperature and particle concentration, liquid, repulsive glass. and attractive gel phases are observed. The dynamics slow down with increasing volume fraction in the liquid phase and reflect a Vogel-Fulcher-Tamann behavior known for fragile glass formers. We find a liquid-glass transition above 50 vol.% that is independent of the particles' concentration and temperature. In an overpacked state at effective volume fractions above 1, the dispersion does not show a liquid phase but undergoes a gel-glass transition at an effective volume fraction of 34 vol.%. At the same concentration, extrema of subdiffusive dynamics are found in the liquid phase at lower weight fractions. We interpret this as dynamic precursors of the glass-gel transition.

Life and death of colloidal bonds control the rate-dependent rheology of gels

Colloidal gels exhibit rich rheological responses under flowing conditions. A clear understanding of the coupling between the kinetics of the formation/rupture of colloidal bonds and the rheological response of attractive gels is lacking. In particular, for gels under different flow regimes, the correlation between the complex rheological response, the bond kinetics, microscopic forces, and an overall micromechanistic view is missing in previous works. Here, we report the bond dynamics in short-range attractive particles, microscopically measured stresses on individual particles and the spatiotemporal evolution of the colloidal structures in different flow regimes. The interplay between interparticle attraction and hydrodynamic stresses is found to be the key to unraveling the physical underpinnings of colloidal gel rheology. Attractive stresses, mostly originating from older bonds dominate the response at low Mason number (the ratio of shearing to attractive forces) while hydrodynamic stresses tend to control the rheology at higher Mason numbers, mostly arising from short-lived bonds. Finally, we present visual mapping of particle bond numbers, their life times and their borne stresses under different flow regimes.

Attractive Pickering Emulsion Gels.

Properties of emulsions highly depend on the interdroplet interactions and, thus, engineering interdroplet interactions at molecular scale are essential to achieve desired emulsion systems. Here, attractive Pickering emulsion gels (APEGs) are designed and prepared by bridging neighboring particle-stabilized droplets via telechelic polymers. In the APEGs, each telechelic molecule with two amino end groups can simultaneously bind to two carboxyl functionalized nanoparticles in two neighboring droplets, forming a bridged network. The APEG systems show typical shear-thinning behaviors and their viscoelastic properties are tunable by temperature, pH, and molecular weight of the telechelic polymers, making them ideal for direct 3D printing. The APEGs can be photopolymerized to prepare APEG-templated porous materials and their microstructures can be tailored to optimize their performances, making the APEG systems promising for a wide range of applications.

The yielding of attractive gels of nanocrystal cellulose (CNC)

The flow behavior of nanocrystalline cellulose (CNC) hydrogels in the presence of a monovalent electrolyte (NaCl) as a function of CNC and salt concentration is explored using a variety of linear and nonlinear rheological tests. We have first observed an apparent “slip yield stress” at small wall shear stress values that is mainly due to the onset of solidlike slippage of the hydrogels before their true yielding and deformation. This flow regime and the “slip yield stress” can be eliminated using a sandpaper of an optimum grit size. At higher wall shear stress values, two yielding points for the CNC/salt network are seen in strain sweep tests due to network disruption and cluster deformation that depend on the concentration of both CNC (1–5 wt. %) and electrolyte (0–100 mM). The first yield stress is due to yielding and flow of clusters, while the second one is due to breakage of clusters to small flocs and individual fibers. These yielding stresses were obtained by a variety of tests including strain amplitude sweep, creep, and steady shear, and their values are compared confirming their existence. Rheo-SALS (small angle light scattering) measurements confirmed structural changes as the scattering patterns change from isotropic to highly anisotropic with an increase of deformation and rate of deformation. Moreover, confocal laser scanning microscopy and polarized microscopy images confirm the gradual breakup of clusters to smaller ones and eventually to nearly individual fibers with an increase in the applied shear strain and rate.

Kinetics of Network Formation and Heterogeneous Dynamics of an Egg White Gel Revealed by Coherent X-Ray Scattering

The kinetics of heat-induced gelation and the microscopic dynamics of a hen egg white gel are probed using x-ray photon correlation spectroscopy along with ultrasmall-angle x-ray scattering. The kinetics of structural growth reveals a reaction-limited aggregation process with a gel fractal dimension of ≈2 and an average network mesh size of ca. 400nm. The dynamics probed at these length scales reveals an exponential growth of the characteristic relaxation times followed by an intriguing steady state in combination with a compressed exponential correlation function and a temporal heterogeneity. The degree of heterogeneity increases with decreasing length scale. We discuss our results in the broader context of experiments and models describing attractive colloidal gels.

Shear driven vorticity aligned flocs in a suspension of attractive rigid rods.

A combination of rheology, optical microscopy and computer simulations was used to investigate the microstructural changes of a semi-dilute suspension of attractive rigid rods in an imposed shear flow. The aim is to understand the relation of the microstructure with the viscoelastic response, and the yielding and flow behaviour in different shear regimes of gels built from rodlike colloids. A semi-dilute suspension of micron sized, rodlike silica particles suspended in 11 M CsCl salt solution was used as a model system for attractive rods' gel. Upon application of steady shear the gel microstructure rearranges in different states and exhibits flow instabilities depending on shear rate, attraction strength, volume fraction and geometrical confinement. At low rod volume fractions, the suspension forms large, vorticity aligned, particle rich flocs that roll in the flow-vorticity plane, an effect that is due to an interplay between hydrodynamic interactions and geometrical confinement as suggested by computer simulations. Experimental data allow the creation of a state diagram, as a function of volume fraction and shear rates, identifying regimes of stable (or unstable) floc formation and of homogeneous gel or broken clusters. The transition is related to dimensionless Mason number, defined as the ratio of shear forces to interparticle attractive force.

A microvolume shear cell for combined rheology and x-ray scattering experiments.

An experimental setup is presented for x-ray scattering studies of soft matter under shear flow that employs a low-background coaxial capillary cell coupled to a high-resolution commercial rheometer. The rotor of the Searle type cell is attached to the rheometer shaft, which allows the application of either steady or oscillatory shear of controlled stress or rate on the sample confined in the annular space between the stator and the rotor. The shearing device facilitates ultrasmall-angle x-ray scattering and ultrasmall-angle x-ray photon correlation spectroscopy measurements with relatively low scattering backgrounds. This enables the elucidation of weak structural features otherwise submerged in the background and probes the underlying dynamics. The performance of the setup is demonstrated by means of a variety of colloidal systems subjected to different rheological protocols. Examples include shear deformation of a short-range attractive colloidal gel, dynamics of dilute colloids in shear flow, distortion of the structure factor of a dense repulsive colloidal suspension, shear induced ordering of colloidal crystals, and alignment of multilamellar microtubes formed by a surfactant-polysaccharide mixture. Finally, the new possibilities offered by this setup for investigating soft matter subjected to shear flow by x-ray scattering are discussed.

Atomic scale investigation of the volume phase transition in concentrated PNIPAM microgels.

Combining elastic incoherent neutron scattering and differential scanning calorimetry, we investigate the occurrence of the volume phase transition (VPT) in very concentrated poly-(N-isopropyl-acrylamide) (PNIPAM) microgel suspensions, from a polymer weight fraction of 30 wt. % up to dry conditions. Although samples are arrested at the macroscopic scale, atomic degrees of freedom are equilibrated and can be probed in a reproducible way. A clear signature of the VPT is present as a sharp drop in the mean square displacement of PNIPAM hydrogen atoms obtained by neutron scattering. As a function of concentration, the VPT gets smoother as dry conditions are approached, whereas the VPT temperature shows a minimum at about 43 wt. %. This behavior is qualitatively confirmed by calorimetry measurements. Molecular dynamics simulations are employed to complement experimental results and gain further insights into the nature of the VPT, confirming that it involves the formation of an attractive gel state between the microgels. Overall, these results provide evidence that the VPT in PNIPAM-based systems can be detected at different time- and length-scales as well as under overcrowded conditions.