Shear Induced Interactions Cause Polymer Compression.

Shear induced particle pressure occurs in concentrated suspensions of particles. Importantly, the significance of the shear induced particle pressure has not been recognized in polymer rheology. The shear induced particle pressure results in an inward pressure on the polymer chains resulting in a shear dependent compressive force. The analytical form of the force balance equations that incorporate the effect of shear induced particle pressure predict a reduced polymer blob size and reducing viscosity with increasing shear rate as has been observed experimentally. Power law behavior is found for the viscosity in accord with the general observations for concentrated polymer rheology.

Combined Fenton and starvation therapies using hemoglobin and glucose oxidase.

Separately, Fenton and starvation cancer therapies have been recently reported as impressive methods for tumor destruction. Here, we introduce natural hemoglobin and glucose oxidase (GOx) for efficient cancer treatment following combined Fenton and starvation therapies. GOx and hemoglobin were encapsulated in zeolitic imidazolate frameworks 8 (ZIF-8) to fabricate a pH-sensitive MOF activated by tumor acidity. In the slightly acidic environment of cancer cells, GOx is released and it consumes d-glucose and molecular oxygen, nutrients essential for the survival of cancer cells, and produces gluconic acid and hydrogen peroxide, respectively. The produced gluconic acid increases the acidity of the tumor microenvironment leading to complete MOF destruction and enhances hemoglobin and GOx release. The Fe ions from the heme groups of hemoglobin also release in the presence of both endogenous and produced H2O2 and generate hydroxyl radicals. The produced OH˙ radical can rapidly oxidize the surrounding biomacromolecules in the biological system and treat the cancer cells. In vitro experiments demonstrate that this novel nanoparticle is cytotoxic to cancer cells HeLa and MCF-7, at very low concentrations (<2 µg mL-1). In addition, the selectivity index values are 5.52 and 11.04 for HeLa and MCF-7 cells, respectively, which are much higher than those of commercial drugs and those of similar studies reported by other research groups. This work thus demonstrates a novel pH-sensitive system containing hemoglobin and GOx for effective and selective cancer treatment using both radical generation and nutrient starvation.

The viscosity-radius relationship for concentrated polymer solutions.

A key assumption of polymer physics is that the random chain polymers extend in flow. Recent experimental evidence has shown that polymer chains compress in Couette flow in a manner counter to expectation. Here, scaling arguments and experimental evidence from the literature are used to determine the relationship between the viscosity, η, and chain radius of gyration, RG. The viscosity-radius of gyration relationship is found to be [Formula: see text] where m([Formula: see text]) is the power law exponent of the viscosity-temperature relationship that depends on the specific polymer-solvent system and the shear rate, [Formula: see text]. The viscosity is shown to be a power law function of the radius, and to decrease with decreasing radius under conditions where the chains are ideal random walks in concentrated solution. Furthermore, this relationship is consistent with both the widely observed viscosity-temperature and viscosity-shear rate behavior observed in polymer rheology. The assumption of extension is not consistent with these observations as it would require that the chains increase in size with increasing temperature. Shear thinning is thus a result of a decreasing radius with increasing shear rate as [Formula: see text] where n is the power law exponent. Furthermore, the thermal expansion coefficients determine the variation in the power law exponents that are measured for different polymer systems. Typical values of n enable the measured reduction in coils size behavior to be fitted. Furthermore, the notion that polymer chains extend to reduce the viscosity implies that an increasing chain size results in a reduced viscosity is addressed. This assumption would require that the viscosity increases with reducing coil radius which is simply unphysical.

Cancer Treatment through Nanoparticle-Facilitated Fenton Reaction.

Currently, cancer is the second largest cause of death worldwide and has reached critical levels. In spite of all the efforts, common treatments including chemotherapy, photodynamic therapy, and photothermal therapy suffer from various problems which limit their efficiency and performance. For this reason, different strategies are being explored which improve the efficiency of these traditional therapeutic methods or treat the tumor cells directly. One such strategy utilizing the Fenton reaction has been investigated by many groups for the possible treatment of cancer cells. This approach is based on the knowledge that high levels of hydrogen peroxide exist within cancer cells and can be used to catalyze the Fenton reaction, leading to cancer-killing reactive oxygen species. Analysis of the current literature has shown that, due to the diverse morphologies, different sizes, various chemical properties, and the tunable structure of nanoparticles, nanotechnology offers the most promising method to facilitate the Fenton reaction with cancer therapy. This review aims to highlight the use of the Fenton reaction using different nanoparticles to improve traditional cancer therapies and the emerging Fenton-based therapy, highlighting the obstacles, challenges, and promising developments in each of these areas.

Targeted Graphene Oxide Networks: Cytotoxicity and Synergy with Anticancer Agents.

An effective strategy to inhibit endocytosis in cancer cells is presented where modified net-type graphene oxide (GO) sheets, bound with multiple cell surface receptors, are introduced and synthesized as novel anticancer agents. The results suggest that the binding connects GO sheets with neighboring lipid rafts, neutralizes endocytosis, and causes metabolic deprivation. As a result, tumor cell survival and proliferation are reduced. Live cell confocal microscopy imaging reveals that GO-PEGFA (folate-PEGylated GO) (PEG, polyethylene glycol) is internalized by tumor cells, while GO-PEGRGD (tripeptide Arg-Gly-Asp PEGylated GO) associates with the external cell membrane (not internalized). In vitro exposure of tumor cells to GO-PEGFA or GO-PEGRGD reduces the cell viability by 35%, compared to 50% reduction using methotrexate (100 µM). The combination of modified GO sheets with methotrexate or doxorubicin shows a greater toxicity (80% reduction in cell viability) than the individual agents. The proposed setup demonstrates a significant synergy in limiting tumor cell growth.

Photophysical and Fluorescence Anisotropic Behavior of Polyfluorene ß-Conformation Films.

We demonstrate a systematic visualization of the unique photophysical and fluorescence anisotropic properties of polyfluorene coplanar conformation (ß-conformation) using time-resolved scanning confocal fluorescence imaging (FLIM) and fluorescence anisotropy imaging microscopy (FAIM) measurements. We observe inhomogeneous morphologies and fluorescence decay profiles at various micrometer-sized regions within all types of polyfluorene ß-conformational spin-coated films. Poly(9,9-dioctylfluorene-2,7-diyl) (PFO) and poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPF) ß-domains both have shorter lifetime than those of the glassy conformation for the longer effective conjugated length and rigid chain structures. Besides, ß-conformational regions have larger fluorescence anisotropy for the low molecular rotational motion and high chain orientation, while the low anisotropy in glassy conformational regions shows more rotational freedom of the chain and efficient energy migration from amorphous regions to ß-conformation as a whole. Finally, ultrastable ASE threshold in the PODPF ß-conformational films also confirms its potential application in organic lasers. In this regard, FLIM and FAIM measurements provide an effective platform to explore the fundamental photophysical process of conformational transitions in conjugated polymer.

Effect of natural biopolymers on amyloid fibril formation and morphology.

Amyloid fibrils are associated with the pathogenesis of protein misfolding diseases such as Alzheimer's disease. These fibrils typically exhibit different morphologies when grown in vitro, and this has been known to affect their biological properties and cytotoxicity. The formation kinetics and resultant morphology of fibrils formed from the model proteins Bovine Insulin and Hen Egg White Lysozyme have been measured. We show that the presence of gum arabic and pectin during fibril formation cause the amyloid fibrils formed to associate into higher order fibrillar aggregates. It is postulated that the carbohydrates act as a template to promote inter-fibril association, resulting in larger, thicker fibrils. This observation provides some insight into the differences in growing amyloid fibrils in vitro in the absence or presence of other high molecular weight compounds. Furthermore, these findings suggest a method of tailoring fibril structure for applications in nanotechnology and bio-template applications.

MOF-Mediated Destruction of Cancer Using the Cell's Own Hydrogen Peroxide.

A novel reduced iron metal-organic framework nanoparticle with cytotoxicity specific to cancer cells is presented. This nanoparticle was prepared via a hydrothermal method, reduced using hydroquinone, and finally conjugated with folic acid (namely, rMOF-FA). The synthesized nanoparticle shows the controlled release of iron in an acidic ex-vivo environment. Iron present on the rMOF-FA and released into solution can react with high levels of hydrogen peroxide found specifically in cancer cells to increase the hydroxyl radical concentration. The hydroxyl radicals oxidize proteins, lipids, and/or DNA within the biological system to decrease cell viability. In vitro experiments demonstrate that this novel nanoparticle is cytotoxic to cancer cells (HeLa) through generation of OH• inside the cells. At low concentrations of rMOF-FA, the cancer cell viability decreases dramatically, with no obvious reduction of normal cell (NIH-3T3) viability. The calculated half-maximum inhibitory concentration value (IC50) was 43 µg/mL for HeLa cells, which was significantly higher than 105 µg/mL for NIH-3T3. This work thus demonstrates a new type of agent for controlled hydroxyl radical generation using the Fenton reaction to kill the tumor cells.

Nanoparticle diffusion in crowded and confined media.

We identify distinct mechanisms controlling slowing of nanoparticle diffusion through complex media featuring both rigid geometrical confinement and soft mobile crowders. Towards this end, we use confocal microscopy and single particle tracking to probe the diffusion of 400 nm nanoparticles suspended in Newtonian water, in a Newtonian glycerol/water mixture, or in a non-Newtonian polymer solution through a model porous medium, a packed bed of microscale glass beads. The mobility of nanoparticles, as quantified by the long-time diffusion coefficient extracted from the particle mean-squared displacement, slows as the average pore size of the packed bed media decreases for both Newtonian and non-Newtonian solutions. The distribution of particle displacements is non-Gaussian, consistent with the spatial heterogeneity of the geometrical confinement imposed by the packed bed. The slowing of nanoparticle mobility in all solutions follows the predictions of models that describe hydrodynamic interactions with the packed bed. In non-Newtonian solutions, depletion interactions due to the polymers near the glass beads result in temporary adsorption of particles onto the bead surface, as indicated by a stretched-exponential distribution of residence times. Our results therefore suggest that the confined diffusive dynamics of nanoparticles in polymer solutions is controlled by two competing mechanisms: hydrodynamic interactions between particles and spatial obstacles, which dictate the long-time slowing of diffusion, and depletion interactions between particles and confining walls due to the macromolecules, which control transient adsorption and hence alter the statistics of the short-time motion.

Flow-induced aggregation of colloidal particles in viscoelastic fluids.

The flow-induced aggregation of dilute colloidal polystyrene nanoparticles suspended in Newtonian and viscoelastic solutions is reported. A rheo-optical method has been used to detect real-time aggregation processes via measuring optical absorption or scattering in a quartz Couette cell. The observed absorbance decreases over time are attributed to the flow-induced coagulation. Numerical simulations show that the aggregation processes still follow the Smoluchowski coagulation equation in a revised version. Suspensions in a series of media are studied to evaluate the effect of the media rheological properties on the particle aggregation. The data shows that elasticity reduces the aggregation while the solution viscosity enhances the aggregation processes.

Alignment of Red Poly[dodecadyin-1,12-diol-bis(4-butoxycarbonyl-methyl-urethane)] in Couette Flow.

The flow-induced alignment of red poly[dodecadyin-1,12-diol-bis(4-butoxycarbonyl-methyl-urethane)] (poly-4BCMU) in chloroform/toluene solution is reported. Absorption spectra have been measured over a range of shear rates in an optically transparent quartz Couette cell. The measured spectra show that the poly-4BCMU structure stays the same in flow, while the measured absorbance anisotropy is attributed to the flow-induced particle alignment in the red form poly-4BCMU solutions. A limiting orientation at shear rates >50 s(-1) is observed. Numerical simulations show that the spectral changes are consistent with the rodlike poly-4BCMU particle having an aspect ratio of 2.9. The dichroic ratio of 1.9 interpreted from the data indicates that the individual poly-4BCMU chains do not aggregate amorphously in the rodlike conformation, rather they show a preferred orientation along the long axis of the prolate aggregates.

Nanoparticle dispersion in disordered porous media with and without polymer additives.

In purely viscous Newtonian fluids, mechanical mixing of the fluid stream as it moves through an unstructured porous medium controls the long-time dispersion of molecular tracers. In applications ranging from environmental remediation to materials processing, however, particles are transported through porous media in polymer solutions and melts, for which the fluid properties depend on the shear rate and extent of deformation. How the flow characteristics of polymer solutions affect the spreading of finite-sized particles remains poorly understood - both on the microscopic scale as local velocity profiles, and on the macroscale as dispersion. Here, we show across a range of flow rates and disordered porous media configurations that the long-time transport coefficients of particles flowed in water, in a viscous Newtonian fluid, and in a non-Newtonian shear-thinning polymer solution collapse onto scaling curves, independent of the fluid rheology. Thus the addition of polymer does not impact nanoparticle dispersion through disordered porous media.

Shear Induced Alignment of Low Aspect Ratio Gold Nanorods in Newtonian Fluids.

The flow-induced alignment of small gold nanorods ranging in aspect ratio from 2.4 to 4.2 in aqueous sucrose solutions is reported. Optical absorption spectra have been measured over a range of shear rates using polarized incident light in an optically transparent quartz Couette cell. The measured spectral changes are directly attributed to the shear-induced anisotropy in the suspension due to particle alignment that saturates at Péclet number of around 200. The measured optical changes are reversible, indicating that the nanorods do not undergo aggregation during measurement. Numerical simulations show that the spectral shifts are consistent with the rods flipping between extreme orientations of the Jeffery's orbits and that the effect of the Brownian motion on the gold nanorods cannot be ignored even at large Péclet number.

A generic class of amyloid fibril inhibitors.

Amyloid fibrils are large ordered fibrillar aggregates formed from mis-folded proteins. A number of human diseases are linked to the presence of amyloid deposits, including Alzheimer's disease, Parkinson's disease and type II diabetes. One therapeutic strategy for treating amyloid related diseases involves inhibiting fibril formation. Amyloid fibrils are ß-sheet rich fibrillar aggregates that associate through hydrophobic interactions between precursor units. In this study, these generic physical properties of amyloid fibrils have been exploited to design a universal class of amphiphilic macromolecular inhibitors. A naturally occurring macromolecule of this structure is arabinogalactan protein (AGP), a component of gum arabic (GA). In addition, two synthetic polymers based on the proposed amphiphilic structure were synthesized and tested. These synthetic mimics, referred to as poly(norbornene glucose ester) (PNGE) and poly(norbornene gluconamide) (PNGA), possess hydrophobic polynorbornene backbones and pendent hydrophilic cyclic and open-chain glucose units, respectively. AGP, PNGE and PNGA all show inhibitory effects on in vitro amyloid fibril formation in bovine insulin (BI), hen egg white lysozyme (HEWL) and amyloid beta 1-40 (Aß) proteins. Circular dichroism (CD) spectra of the proteins in the presence of the inhibitors suggests that amyloid fibril formation is inhibited by stabilization of the native α-helices of the proteins, as well as binding of the inhibitors to the ß-sheet precursors. Based upon these results, glycosylated hydrophobic macromolecules are identified as a promising class of therapeutic agents for amyloid related diseases. Furthermore, we have determined that the intensity of the fluorescent probe thioflavin T (ThT) is dependent on both fibril morphology and the presence of the inhibitors, and is therefore not a quantitative measure of protein conversion to fibrils.

Controlled Formation of Star Polymer Nanoparticles via Visible Light Photopolymerization.

A recently developed visible light mediated photocontrolled radical polymerization technique using trithiocarbonates (i.e., conventional RAFT agents) as the sole control agent in the absence of additional photoinitiators or catalysts is utilized for the synthesis of core cross-linked star (CCS) polymer nanoparticles. The attractive features of this photopolymerization system, including high end-group fidelity at (near) complete monomer conversion, are exploited to facilitate a high-yielding, one-pot pathway toward well-defined star polymer products. Moreover, reinitiation of the photoactive trithiocarbonate moieties from within the star core is demonstrated to form (pseudo)miktoarm stars via an "in-out" approach, showing extremely high initiation efficiency (95%).

Study of electrical conductivity response upon formation of ice and gas hydrates from salt solutions by a second generation high pressure electrical conductivity probe.

We recently reported the development of a high pressure electrical conductivity probe (HP-ECP) for experimental studies of formation of gas hydrates from electrolytes. The onset of the formation of methane-propane mixed gas hydrate from salt solutions was marked by a temporary upward spike in the electrical conductivity. To further understand hydrate formation a second generation of window-less HP-ECP (MkII), which has a much smaller heat capacity than the earlier version and allows access to faster cooling rates, has been constructed. Using the HP-ECP (MkII) the electrical conductivity signal responses of NaCl solutions upon the formation of ice, tetrahydrofuran hydrates, and methane-propane mixed gas hydrate has been measured. The concentration range of the NaCl solutions was from 1 mM to 3M and the driving AC frequency range was from 25 Hz to 5 kHz. This data has been used to construct an "electrical conductivity response phase diagrams" that summarize the electrical conductivity response signal upon solid formation in these systems. The general trend is that gas hydrate formation is marked by an upward spike in the conductivity at high concentrations and by a drop at low concentrations. This work shows that HP-ECP can be applied in automated measurements of hydrate formation probability distributions of optically opaque samples using the conductivity response signals as a trigger.

A brief overview of amyloids and Alzheimer's disease.

Amyloid fibrils are self-assembled fibrous protein aggregates that are associated with a number of presently incurable diseases such as Alzheimer's and Parkinson's disease. Millions of people worldwide suffer from amyloid diseases. This review summarizes the unique cross-ß structure of amyloid fibrils, morphological variations, the kinetics of amyloid fibril formation, and the cytotoxic effects of these fibrils and oligomers. Alzheimer's disease is also explored as an example of an amyloid disease to show the various approaches to treat these amyloid diseases. Finally, this review investigates the nanotechnological and biological applications of amyloid fibrils; as well as a summary of the typical biological pathways involved in the disposal of amyloid fibrils and their precursors.

The potential role of free chitosan in bone trauma and bone cancer management.

Bone defects caused by fractures or cancer-mediated destruction are debilitating. Chitosan is commonly used in scaffold matrices for bone healing, but rarely as a free drug. We demonstrate that free chitosan promotes osteoblast proliferation and osteogenesis in mesenchymal stem cells, increases osteopontin and collagen I expression, and reduces osteoclastogenesis. Chitosan inhibits invasion of endothelial cells, downregulating uPA/R, MT1-MMP, cdc42 and Rac1. Better healing of bone fractures with greater trabecular bone formation was observed in mice treated with chitosan. Chitosan induces apoptosis in osteotropic prostate and breast cancer cells via caspase-2 and -3 activation, and reduces their establishment in bone. Chitosan is pro-apoptotic in osteosarcoma cells, but not their normal counterpart, osteoblasts, or chondrosarcoma cells. Systemic delivery of chitosan does not perturb angiogenesis, bone volume or instinctive behaviour in pregnant mice, but decreases foetal length and changes pancreatic secretory acini. With certain controls in place, chitosan could be useful for bone trauma management.

Electric field induced changes in protein conformation.

The effect of a low strength oscillating electric field on the conformation of Bovine Serum Albumin (BSA) and Lysozyme in solution has been measured. A purpose built cell has been used to measure the real time autofluorescence and Circular Dichroism of the protein solutions exposed to electric fields of differing strength and frequency. Exposure to the electric fields results in protein unfolding for both Lysozyme and BSA. The applied field strengths are extremely small compared to the protein inter-chain intra-molecular forces. We propose a model whereby the electrophoretic motion of the proteins leads to a frictional force that results in protein unfolding. For BSA and Lysozyme in the electric fields used in this study, the shear rates at the protein surface under electrophoretic motion are of order 10(3) and 10(4) s(-1) respectively. Prolonged electric field exposure results in significant frictional energy dissipation in the proteins. The energy dissipated in the proteins results in protein unfolding, which is a critical initial step for protein aggregation and potentially amyloid fibril formation.

The effect of concentration, temperature and stirring on hen egg white lysozyme amyloid formation.

Lysozyme is associated with hereditary systemic amyloidosis in humans. Hen egg white lysozyme (HEWL) has been extensively studied as an amyloid forming protein. In this study, we investigated HEWL amyloid formation over a range of temperatures at two stirring speeds and at low concentrations to avoid gel formation. The amyloid fibril formation was found to follow first order kinetics with the rate determining step being the unfolding of the lysozyme. Both the rate of formation and final amount of amyloid formed show maxima with temperature at approximately at 65 °C. CD measurements show that the lysozyme is unfolded by 55 °C. The decrease in amyloid formation at temperatures above 65 °C is attributed to competing amorphous aggregation. The majority of the non-fibrillar aggregates are small and uniform in size with a few larger amorphous aggregates observed in the AFM images.