Shaped Charge Research Articles

One-Dimensional Electrophoresis Using Nondenaturing Conditions.

Electrophoresis is used to separate complex mixtures of proteins (e.g., from cells, subcellular fractions, column fractions, or immunoprecipitates), to investigate subunit composition, track post-translational modifications, and verify identity and homogeneity of protein samples. It can also serve to purify proteins for use in further applications. In polyacrylamide gel electrophoresis, proteins migrate in response to an electrical field through pores in a polyacrylamide gel matrix; pore size decreases with increasing acrylamide concentration. Nondenaturing or "native" electrophoresis-i.e., electrophoresis in the absence of denaturants such as detergents and urea-is an often-overlooked technique for determining the native size, subunit structure, and optimal separation of a protein. Because mobility depends on the size, shape, and intrinsic charge of the protein, nondenaturing electrophoresis provides a set of separation parameters distinctly different from mainly size-dependent denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis and charge-dependent isoelectric focusing. Two protocols are presented below. Continuous PAGE is highly flexible, permitting cationic and anionic electrophoresis over a full range of pH. The discontinuous procedure is limited to proteins negatively charged at neutral pH but provides high resolution for accurate size calibration.

Nanostructured pH-responsive biocompatible chitosan coated copper oxide nanoparticles: A polymeric smart intracellular delivery system for doxorubicin in breast cancer cells

In this study, we report a novel feasible single step reduction method for the active synthesis of biocompatible chitosan coated copper oxide nanoparticles (Cs-CuO NPs), for loading and delivery of doxorubicin (DOX) into breast cancer cells. The formulated nanoparticles (NPs) were characterized by size, shape and surface charge using various sophisticated instruments. Interestingly, these formulated particles showed profound drug loading activity and also showed its versatile nature of DOX release at different pH which makes them as ideal particles for breast cancer therapy. Intracellular uptake was evaluated through fluorescence microscopy studies with the help of coumarin. Morphological and apoptotic studies with the DOX-Cs-CuO NPs on MCF-7 cells showed its ability to induce apoptosis in breast cancer cells, which was clearly substantiated by ROS generation with the loss of mitochondrial membrane potential. Our results clearly showed the therapeutic nature of novel biocompatible Cs-CuO NPs in delivering DOX with a pH-dependent manner.

Strategies to improve tumor penetration of nanomedicines through nanoparticle design.

Nanoparticles (NPs) have emerged as an effective means to deliver therapeutic drugs for cancer treatment, as they can preferentially accumulate at tumor site through the enhanced permeability and retention effect. Various forms of NPs including liposomes, polymeric micelles, and inorganic particles have been used for therapeutic applications. However, the therapeutic benefits of nanomedicines are suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumor penetration can be a vital obstacle. Tumor develops characteristic pathological environment, such as abnormal vasculature, elevated interstitial fluid pressure, and dense extracellular matrix, which intrinsically hinder the transport of nanomedicines in the tumor parenchyma. The physicochemical properties of the NPs such as size, shape, and surface charge have profound effect on tumor penetration. In this review, we will highlight the factors that affect the transport of NPs in solid tumor, and then elaborate on designing strategies to improve NPs' penetration and uniform distribution inside the tumor interstitium. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Зажигательное действие кумулятивных зарядов по жидкому топливу

Зажигательное действие кумулятивных зарядов по жидкому топливу

Hyaluronic Acid Layered Chimeric Nanoparticles: Targeting MAPK-PI3K Signaling Hub in Colon Cancer Cells.

Colon cancer has emerged as one of the most devastating diseases in the whole world. Mitogen-activated protein kinase (MAPK)-phosphatidylinsitol-3-kinase (PI3K) signaling hub has gained lots of attention due to its deregulation in colon cancer cells. However, selective targeting of oncogenic MAPK-PI3K hub in colon cancer has remained highly challenging, hence it has mostly been unexplored. To address this, we have engineered a hyaluronic acid layered lipid-based chimeric nanoparticle (HA-CNP) consisting of AZD6244 (MAPK inhibitor), PI103 (PI3K inhibitor), and cisplatin (DNA impairing drug) ratiometrically in a single particle. Electron microscopy (field emission scanning electron microscopy and atomic force microscopy) and dynamic light scattering were utilized to characterize the size, shape, morphology, and surface charge of the HA-CNPs. Fluorescent confocal laser scanning microscopy and flow cytometry analysis confirmed that HA-CNPs were taken up by HCT-116 colon cancer cells by merging of clathrin and CD44 receptor-mediated endocytosis along with macropinocytosis to home into acidic organelles (lysosomes) within 1 h. A gel electrophoresis study evidently established that HA-CNPs simultaneously inhibited MAPK-PI3K signaling hub with DNA damage in HCT-116 cells. These HA-CNPs stalled the cell cycle into G0/G1 phase, leading to induction of apoptosis (early and late) in colon cancer cells. Finally, these HA-CNPs exerted remarkable cytotoxicity in HCT-116 colon cancer cells at 24 h compared to that of the free triple drug cocktail as well as HA-coated dual drug-loaded nanoparticles without showing any cell death in healthy L929 fibroblast cells. These HA-coated CNPs have potential to be translated into clinics as a novel platform to perturb various oncogenic signaling hubs concomitantly toward next-generation targeted colon cancer therapy.

Systematic Study of Aluminum Nanoclusters and Anion Adsorbates.

The interactions between aqueous aluminum (Al) nanoclusters and ions in solution influence the reactivity of nanomaterials in natural waters and are crucial to the targeted syntheses of aluminum oxides. To contribute to the fundamental understanding of how both anion and Al-nanocluster properties affect the interactions, we carry out systematic modeling studies that employ density functional theory calculations embedded in a continuum solvent model. Energetic and electronic structure analysis is applied toward delineating the interactions of a range of probe adsorbate anions with Al nanoclusters to elucidate how small molecules may react with naturally occurring nanomaterials. The study spans seven small molecules on three model Al nanoclusters. Using this ion set, we correlate the size, shape, and formal charge of the adsorbate to the trends in adsorption energies. A key finding is that the collective effects of exposed oxygen functional groups, i.e., the distribution of functional groups, dictates the electrostatic potential of the nanocluster surface, which, in turn, controls trends in anion adsorption. The computed adsorption and deprotonation trends are correlated to known synthetic routes of Al-nanocluster formation and subsequent crystallization to give insight into the potential optimization of synthetic conditions.

Action Mechanism of Imposed Magnetic Field on Shaped Charge Jet

Action Mechanism of Imposed Magnetic Field on Shaped Charge Jet

In vitro release and cytotoxicity of cisplatin loaded methoxy poly (ethylene glycol)-block-poly (glutamic acid) nanoparticles against human breast cancer cell lines

Different formulations of methoxy poly (ethylene glycol)-block-poly (glutamic acid) (mPEG-b-PLG) were successfully synthesized. Drug loading, in vitro release and cytotoxicity of Cis-Diaminodichloro platinum (II) (CDDP, cisplatin) loaded nanoparticles were investigated. The synthesized polymers were structurally characterized by Proton Nuclear Magnetic Resonance (1H NMR) and Fourier Transform Infra-Red (FTIR). Number average molecular weight (Mn), degree of polymerization (DP) and poly dispersity index (PDI) were determined. Drug loading contents and drug loading efficiency were quantified. The drug loaded nanoparticles were developed in small size, uniform shape and with slightly negative zeta potential. There was more release at lysosomal pH (5.5) as compared to physiological pH (7.4). The release was in a sustained and controlled manner which was consistent with the in vitro longevity of the nanoparticles. The effect of glutamic acid moieties on in vitro release was also investigated. There was dose and time dependent cell proliferation inhibition of the free drug and drug loaded nanoparticle. The biocompatibility, optimum size, shape and surface charge of the developed nanoparticles make them an efficient drug delivery carrier.

Influence of shape and surface charge on the sedimentation of spheroidal, cubic and rectangular cuboid particles

This study investigated the complex settling behaviour of colloidal particles with varied surface charge and shape factors, of specific relevance to nuclear waste processing. Caesium phosphomolybdate (CPM), zirconium molybdate (ZM) and zirconium citromolybdate (ZMCA) were firstly synthesised, producing spheroidal, cubic and rectangular cuboidal morphologies respectively, and compared to agglomerated titania. While zeta-potential measurements indicated all simulant particles attained low isoelectric points, surface group leaching rendered suspensions very acidic, with CPM around its IEP, and ZM/ZMCA stable and positively charged. In sedimentation tests at various concentrations in water and 2M HNO3, CPM and titania were found to settle with extremely high hindered settling exponents, consistent with aggregated structures. Exponents for ZM and ZMCA in water were both also well above values for spherical particles; however, this was assumed to be due to heightened drag effects from relative shape factors, rather than aggregation. ZMCA in particular showed a very high exponent of ~11.4, due to the propensity for the rod-like particles to settle in a flat conformation. For ZM in acid, double layer compression from the high electrolyte aggregated the dispersions, correlating to a significant increase in the settling exponent. An extended Stokes relationship was additionally used to understand theoretical limits of shape and aggregation on particle size prediction from hindered settling curves. Importantly, calculated sizes were consistent for the stable ZM and ZMCA in water, despite their non-sphericity and enhanced drag. The relationship failed however with agglomerated suspensions, highlighting its application as a general stability test for sedimenting dispersions.

Time-Resolved Linear Dichroism Measurements of Carbonmonoxy Myoglobin as a Probe of the Microviscosity in Crowded Environments.

The distribution of viscosities in living cells is heterogeneous because of the different sizes and natures of macromolecular components. When thinking about protein folding/function processes in such an environment, the relevant (micro)viscosity at the micrometer length scale is necessarily distinguished from the bulk (macro)viscosity. The concentration dependencies of microviscosities are determined by a number of factors, such as electrostatic interactions, van der Waals forces, and excluded volume effects. To explore such factors, the rotational diffusion time of myoglobin in the presence of varying concentrations of macromolecules that differ in molecular weight (dextran 6000, 10 000, and 70 000), shape (dextran versus Ficoll), size, and surface charge is measured with time-resolved linear dichroism spectroscopy. The results of these studies offer simple empirically determined linear and exponential functions useful for predicting microviscosities as a function of concentration for these macromolecular crowders that are typically used to study crowding effects on protein folding. To understand how relevant these microviscosity measurements are to intracellular environments, the TRLD results are discussed in the context of studies that measure viscosity in cells.

The role of supporting electrolyte in heterogeneous electron transfer

The effects of supporting electrolyte on the kinetics of the elementary step of electron transfer are considered as unavoidable interplay of interfacial phenomena and ionic equilibria in solution. For the former, the problems to separate contributions of electrostatic electrode-reactant interactions and specific adsorption are addressed, and various aspects of the traditional Frumkin correction (“psi-prime effect”) are discussed. The construction of corrected Tafel plots is shown to be a procedure containing the internal contradiction resulting in an uncertainty. This uncertainty can be eliminated by combining the principles of traditional analysis of the “double layer” effects with physical theory instead of phenomenological approaches. Specific manifestations of parallel electron transfer to an ensemble of reacting species are presented in the context of “mean reactant charge in solution bulk.” The approach to account for non-spherical shape and inhomogeneous charge distribution in reacting species is considered in terms of “molecular psi-prime effect.” Finally, some comments are given on analogy of “double layer” effects at metal/solution interface and interfacial phenomena specific for more complex and highly relevant electrochemical systems.

Research advances in separation and determination of metallic nanomaterials in the environment

With the mass production and wide application of metallic nanoparticles (MNPs), there is a likelihood of their release into the environment, and therefore considerably increased potential adverse effects on both ecosystem and human health. To understand their occurrence, distribution, transport, fate, effects and biosafety, it is of great importance to develop methods for efficient and sensitive determination of MNPs in the environment. Unlike traditional pollutants, the composition, structure, species and size of MNPs have remarkable impacts on their environmental processes and biological effects, thus it is necessary to determine their composition and concentration, as well as to characterize their size, shape and surface charge. Here, we review the updated methods for analysis of MNPs in the environment in the past ten years, which can be cataloged into the extraction and preconcentration methods, or the separation and determination methods. Extraction and preconcentration methods, including cloud point extraction (CPE), liquid liquid extraction (LLE) and solid phase extraction (SPE), can selectively separate the MNPs from the matrices and therefore enhance the detection limit. However, these methods are unable to separate different sized MNPs, and further characterization techniques are needed to obtain the detailed information on the MNP size and shape. Combination of the size fractionation techniques, such as chromatographic methods, electrophoresis and field flow fractionation (FFF), with highly sensitive detectors like inductively coupled plasma mass spectrometry (ICP-MS) are highly promising in assessment of size and shape-related information of the MNPs and their aggregates. Unfortunately, the hyphenated techniques are difficult to satisfy the requirement of MNP determination at the environmental levels. Single particle ICP-MS (spICP-MS) is an elegant method for simultaneous determination of the size distribution and concentration of MNPs in the environment, but it still remians a great challenge to determine the small sized MNPs ( Currently, great achievements have been gained in the analysis of MNPs. To accurately appraise the exposure risks for environmental and human health arising from MNP production, application and disposal, however, some issues are still needed to be solved, mainly including the following four aspects: (1) relatively complete and scientific standard methods for analysis of MNPs in the environment, covering sampling, pretreatment, quantification and characterization, still require further development; (2) methods for extraction of MNPs from soil and sediment, which can maintain the original size and shape of MNPs, are urgently needed; (3) the detection limits of the existing techniques are still too high to satisfy the determination of MNPs at the environmental levels, therefore, methods with a high sensitivity are desiderated; (4) the co-existance of natural MNPs greatly complicates the risk assessment of the engineered MNPs in the environment, therefore, it is of vital importance to develop techniques to distinguish between natural and engineered MNPs.

Impact performance of explosively formed projectile (EFP) into concrete targets

This paper addresses the impact performance of explosively formed projectile (EFP) formed by shaped charge (SC) on the concrete targets. Firstly, a series of EFP penetration/perforation test on concrete targets are conducted. By assessing the dimensions of front spalling and rear scabbing craters as well as the penetration borehole, the influences of SC liner material, concrete type and target configuration (monolithic and spaced) on the target damage are experimentally discussed. Secondly, by utilizing the multi-material Arbitrary Lagrange-Euler (ALE) algorithm, Fluid-Structure Interaction (FSI) method and erosion algorithm implemented in the finite element (FE) code LS-DYNA, and describing the concrete targets with the original and modified HJC models, the formation and impact processes of EFP are well reproduced. Furthermore, based on the validated constitutive models and the corresponding parameters, the influences of explosive type, liner configuration and thickness, first concrete panel and air interlayer thicknesses of spaced target on the impact performance of EFP are further discussed. The derived conclusions could provide helpful references for the analysis and design of the concrete protective structures, and the evaluation of the ballistic performance of EFP.

Zein/caseinate/pectin complex nanoparticles: Formation and characterization

In this study, pectin was used as coating material to form zein/caseinate/pectin complex nanoparticles through pH adjustment and heating treatment for potential oral delivery applications. The preparation conditions were studied by applying heating treatment at different pHs, either the isoelectric point of zein (pH 6.2) or caseinate (pH 4.6), or consecutively at both pHs. The particulate characteristics, including particle size, polydispersity index, and zeta potential were monitored for complex nanoparticles formed under different preparation conditions. The complex nanoparticles generally exhibited particle size smaller than 200nm with narrow distribution, spherical shape, and strong negative charge. Fourier transform infrared and fluorescence spectroscopy revealed that hydrophobic interactions and hydrogen bonds were involved in the formation of complex nanoparticles, in addition to electrostatic interactions. Fresh colloidal dispersion and freeze-dried powders varied in their morphology, depending on their preparation conditions. Our results suggested that heating pH and sequence significantly affected the morphology of complex nanoparticles, and pectin coating exerted stabilization effect under simulated gastrointestinal conditions. The present study provides insight into the formation of protein/polysaccharide complex nanoparticles under different preparation conditions.

Nanogold - Biological effects and occupational exposure levels

Nanogold has different properties and biological activity compared to metallic gold. It can be applied in many fields, such as medicine, laboratory diagnostics and electronics. Studies on laboratory animals show that nanogold can be absorbed by inhalation and ingestion. It can penetrate deep into the epidermis and dermis, but there is no evidence that it is absorbed through the skin. Gold nanoobjects accumulate mainly in the liver and spleen, but they can also reach other internal organs. Nanogold can cross the blood-brain and blood-placenta barriers. Toxicokinetics of nanogold depends on the particle size, shape and surface charge. In animals exposure to gold nanoparticles via inhalation induces slight changes in the lungs. Exposure to nanogold by the oral route does not cause adverse health effects in rodents. In animals after injection of gold nanoobjects changes in the liver and lungs were observed. Nanogold induced genotoxic effects in cells, but not in animals. No adverse effects on the fetus or reproduction were found. There are no carcinogenicity studies on gold nanoparticles. The mechanism of toxicity may be related to the interaction of gold nanoobjects with proteins and DNA, and it leads to the induction of oxidative stress and genetic material damage. The impact of nanostructures on human health has not yet been fully understood. The person, who works with nanomaterials should exercise extreme caution and apply existing recommendations on the evaluation of nanoobjects exposure. The risk assessment should be the basis for taking appropriate measures to limit potential exposure to nanometals, including nanogold. Med Pr 2017;68(4):545-556.

The effect of concrete damage on the penetration depth by the tandem projectiles

Tandem projectile is one approach of the development of anti-structure concrete projectile, which is made of the forward shape charge and the follow-through projectile. In this paper, in order to study the performance of anti-structure tandem projectiles, experimental and numerical analyses of the penetration process were performed for forward shape charge with conical copper liner hitting into the concrete targets. Having a well agreement, numerical and empirical results indicate that a forward shape charge with a conical copper liner will make appropriate tunnel diameter through the concrete targets. Following the validation of the applied numerical method, numerical simulations were conducted for the penetration of the follow-through projectile, by three different concrete targets: undamaged concrete, pre-drilled concrete, and damaged pre-drilled concrete. The parametric results show that the damaged pre-drilled concrete affects the penetration depth and residual velocity of the follow-through projectile significantly.

Parameters affecting the transscleral delivery of two positively charged proteins of comparable size

Apart from molecular weight and net surface charge, there are other macromolecule-related factors that could, in principle, influence their diffusion across biological tissues, such as shape, conformability, water solubility and surface charge distribution.Lysozyme and cytochrome c, proteins with comparable molecular weight, isoelectric point and net surface charge in physiological conditions (approx. +7.8), are suitable model compounds for comparative studies, in particular to find out if other properties can have a role in the permeation across the sclera. The comparison between lysozyme and cytochrome c permeability was conducted by studying the permeation across the sclera and the choroid-Bruch’s membrane and the diffusion across a hyaluronan gel-matrix. Melanin binding tests and the measurement of the electroosmosis flow during transscleral iontophoresis allowed for the evaluation of macromolecules affinity for the ocular tissues. Finally, anodal iontophoresis was applied to further confirm the interaction of the two proteins with the sclera.The data here collected show that two proteins with very similar MW, p Ka and charge can display very different diffusion properties across biological barriers. In particular, these differences can be attributed to a different interaction with specific components of ocular tissues: while the interaction with melanin and collagen fibers is apparently the same for the two molecules, a relevant difference was found in case of hyaluronic acid. Considering also literature evidences, the important parameters that can be responsible for this different affinity are molecular shape (spherical for cytochrome c vs prolate for lysozyme) and a combination of hydrophobic and electrostatic interactions that depends on the surface charge distribution. The interactions between sclera components and lysozyme are relatively strong and were not altered by the application of electric current.

Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

BackgroundNanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3).ResultsAs a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents.ConclusionsOur results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.

Asymmetrical nanopores in track membranes: Fabrication, the effect of nanopore shape and electric charge of pore walls, promising applications

The properties of asymmetrical nanopores prepared by chemical etching of tracks of accelerated heavy ions are studied. Procedures are developed for controlling the size and shape of pores within wide limits. The presence of charged functional groups on pore walls is an intrinsic property of track membranes, which makes them a convenient object for studying electrokinetic phenomena in nanocapillaries. In electrolyte solutions, the asymmetrical “track” membranes demonstrate the diode effect. Two methods for fabricating asymmetrical nanopores in polyethylene terephthalate films are proposed and introduced into practice. Specific features of both methods, their advantages and drawbacks are considered. In addition to the brief survey of available information on diode-like track membranes, the new results on the mechanism of pore formation and the peculiarities of their geometry and electrokinetic properties are discussed. The emerging and potential applications of track membranes with asymmetrical pores are discussed briefly.

Simulation study on the structural properties of colloidal particles with offset dipoles

A major research theme in materials science is determining how the self-assembly of new generations of colloidal particles of complex shape and surface charge is guided by their interparticle interactions. In this paper, we describe results from quasi-2D Monte Carlo simulations of systems of colloidal particles with offset transversely-oriented extended dipole-like charge distributions interacting via an intermediate-ranged Yukawa potential. The systems are cooled slowly through an annealing procedure during which the temperature is lowered in discrete steps, allowing the system to equilibrate. We perform ground state calculations for two, three and four particles at several shifts of the dipole vector from the particle center. We create state diagrams in the plane spanned by the temperature and the area fraction outlining the boundaries between fluid, string-fluid and percolated states at various values of the shift. Remarkably we find that the effective cooling rate in our simulations has an impact on the structures formed, with chains being more prevalent if the system is cooled quickly and cyclic structures more prevalent if the system is cooled slowly. As the dipole is further shifted from the center, there is an increased tendency to assemble into small cyclic structures at intermediate temperatures. These systems further self-assemble into open lattice-like arrangements at very low temperatures. The novel structures identified might be useful for photonic applications, new types of porous media for filtration and catalysis, and gel matrices with unusual properties.