Amphiphilic Shell Research Articles

Lipoproteins as Drug Carriers for Cyclosporine A: Optimization of the Entrapment.

Lipoproteins are natural nanostructures responsible for the transport of cholesterol and other lipids in the blood. They are characterized by having a lipophilic core surrounded by an amphiphilic shell composed of phospholipids, cholesterol and one or more apolipoproteins. Being endogenous carriers makes them suitable for drug delivery purposes. Here, we investigate the effect of lipoproteins' intricate composition on the entrapment efficiency of a model drug "Cyclosporine A" into the different types of lipoproteins, namely, HDL, LDL and VLDL. It was observed that the protein content of the lipoproteins had the highest effect on the entrapment of the drug with a correlation coefficient of 0.80, 0.81 and 0.96 for HDL, LDL and VLDL respectively. This was even confirmed by the effect of plasma on the association rate of lipoproteins and the drug. The second effective factor is the cholesterol concentration, while triglycerides and phospholipids had a negligible effect.

Interrogating the impact of aggregation‐induced emission nanoparticles on in vitro protein stability, ex vivo protein homeostasis, and in vivo biocompatibility

AbstractAggregation‐induced emission (AIE) materials offer promising perspectives in disease diagnosis and therapeutics given their unique optical and photochemical properties. A key step toward translational applications for AIE materials is to systematically and vigorously evaluate their biosafety and biocompatibility. While previous studies focus on cellular viability and toxicity, the impact of AIE materials on detailed stress responses manifesting cellular fitness has been less explored. Herein, this work provides the first piece of evidence to support amphiphilic functionalization of AIE nanoparticles minimizes the deterioration on proteome stability and cellular protein homeostasis (proteostasis). To this end, four scaffolds of AIE molecules were prepared, further functionalized into eight nanoparticles with two amphiphilic shells respectively, and characterized for their physicochemical properties. Thermal shift assay quantitatively demonstrates that AIE materials after amphiphilic functionalization into nanoparticles enhance proteome thermodynamic stability and ameliorate proteome aggregation propensity in cellular lysate, echoed by cell viability and fractionation experiments. Intriguingly, poor polydispersity index (PDI) of functionalized nanoparticles exaggerates their retention and aggregation in the cell. Comparative proteomic analysis uncovers that amphiphilic functionalization of AIE materials can minimize the deterioration of cellular protein homeostasis network. Finally, vigorous interrogation of functionalized AIE nanoparticles in mice model reveals the complexity of factors affecting the biocompatibility profiles in vivo, including materials’ size, PDI, and treatment frequencies. Overall, amphiphilic functionalization of AIE materials into nanoparticles is necessary to maintain proteome stability and balance cellular protein homeostasis.

Amphiphilic shell nanomagnetic adsorbents for selective and highly efficient capture of low-density lipoprotein from hyperlipidaemia serum.

Removal of low-density lipoprotein (LDL) from hyperlipemia patients' blood represents an effective approach to prevent the progression of atherosclerotic cardiovascular disease. Based on the LDL structural characteristics and intermolecular interactions, a tailored nano-adsorbent (Fe3O4@SiO2@PAA-PE) was prepared aimed at the removal of LDL from hyperlipemia serum with high selectivity. The core-shell structured magnetic nanoparticles were embedded in an amphiphilic layer composed of hydrophilic poly(acrylic acid) and lipophilic phospholipids to provide multifunctional binding for LDL particles. The results of dynamic light scattering, water contact angle and zeta-potential measurements, thermal gravimetric analysis, and X-ray photoelectron spectroscopy together with Fourier transform infrared spectroscopy confirmed the core-shell structured nanoparticles bearing amphiphilic poly acrylic acid and phospholipid molecules. Because of the superior electronegativity of the functional layer, the nano-adsorbent demonstrated favorable adsorption selectivity against high-density lipoprotein, which possesses a similar structure to LDL but has a cardio-protective function in the human body. The respective adsorption capacity of Fe3O4@SiO2@PAA-PE towards LDL, total cholesterol and triglycerides reached up to 6.26 mg g-1, 8.41 mg g-1 and 9.19 mg g-1, which was 7.03, 9.45 and 10.32 times that towards HDL (0.89 mg g-1). The kinetic and isothermal studies revealed that multiple interactions containing both physical and chemical adsorption occurred in the binding procedure between LDL and Fe3O4@SiO2@PAA-PE, and chemical adsorption may play a more predominant role in LDL adsorption. The nano-adsorbent also had negligible effects on blood cells, and possessed satisfactory recyclability, low cytotoxicity and hemolysis ratios, indicating its good application prospects as a hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Multivariable Dependence of Acoustic Contrast of Fluorocarbon and Xenon Microbubbles under Flow

Microbubbles (MBs) are 1 to 10 µm gas particles stabilized by an amphiphilic shell capable of responding to biomedical ultrasound with strong acoustic signals, allowing them to be commonly used in ultrasound imaging and therapy. The composition of both the shell and the core determines their stability and acoustic properties. While there has been extensive characterization of the dissolution, oscillation, cavitation, collapse and therefore, ultrasound contrast of MBs under static conditions, few reports have examined such behavior under hydrodynamic flow. In this study, we evaluate the interplay of ultrasound parameters (five different mechanical indices [MIs]), MB shell parameter (shell stiffness), type of gas (perfluorocarbon for diagnostic imaging and xenon as a therapeutic gas), and a flow parameter (flow rate) on the ultrasound signal of phospholipid-stabilized MBs flowing through a latex tube embedded in a tissue-mimicking phantom. We find that the contrast gradient (CG), a metric of the rate of decay of contrast along the length of the tube, and the contrast peak (CP), the location where the maximum contrast is reached, depend on the conditions of flow, imaging, and MB material. For instance, while the contrast near the flow inlet of the field of view is highest for a softer shell (dipalmitoylphosphatidylcholine [DPPC], C16) than for stiffer shells (distearoylphosphatidylcholine [DSPC], C18, and dibehenoylphosphatidylcholine [DBPC], C22), the contrast decay is also faster; stiffer shells provide more resistance and hence lead to slower MB dissolution/destruction. At higher flow rates, the CG is low for a fixed length of time because each MB is exposed to ultrasound for a shorter period. The CG becomes high for low flow rates, especially at high incident pressures (high MI), causing more MB destruction closer to the inlet of the field of view. Also, the CP shifts toward the inlet at low flow rates, high MIs, and low shell stiffness. We also report the first demonstration of sustained ultrasound flow imaging of a water-soluble, therapeutic gas MB (xenon). We find that an increased MB concentration is necessary for obtaining the same signal magnitude for xenon MBs. In summary, this study builds a framework depicting how multiple variables simultaneously affect the evolution of MB ultrasound contrast under flow. Depending on the MB composition, imaging conditions, transducer positioning, and image processing, building on such a framework could potentially allow for extraction of additional diagnostic information than is commonly analyzed for physiological flow.

Eco-Friendly Bioinspired Interface Design for High-Performance Cellulose Nanofibril/Carbon Nanotube Nanocomposites.

Inspired by a wood-like multicomponent structure, an interface-reinforced method was developed to fabricate high-performance cellulose nanofibril (CNF)/carbon nanotube (CNT) nanocomposites. Holocellulose nanofibrils (HCNFs) with core-shell structure were first obtained from bagasse via mild delignification and mechanical defibration process. The well-preserved native hemicellulose as the amphiphilic shell of HCNFs could act as a binding agent, sizing agent, and even dispersing agent between HCNFs and CNTs. Remarkably, both the tensile strength at high relative humidity (83% RH) and electrical conductivity of the HCNF/CNT nanocomposites were significantly improved up to 121 MPa and 321 S/m, respectively, demonstrating great superiority compared to normal CNF/CNT composite films. Furthermore, these HCNF/CNT composites with outstanding integrated performances exhibited great potential in the field of flexible liquid sensing.

Integrated fast-mass transfer and high Ti-sites utilization into hybrid amphiphilic TS@PMO catalyst towards efficient solvent-free methyl oleate epoxidation

For solvent-free catalytic oxidations, low efficiency resulted from poor mass transfer and insufficient utilization of active centers remains a tough problem. Herein, we demonstrate a novel hybrid core-shell catalyst (TS@PMO) with an amphiphilic shell and a Ti-surface-enriched mesoporous TiO2-SiO2 (TS) core to address this challenge. Such TS@PMO realizes its amphiphilicity via an ex situ formed periodic mesoporous organosilica (PMO) shell. Simultaneously, by a unique etching effect induced by organic precursor growth on [SiO4] tetrahedra in TS core, active Ti sites are facilely enriched in near-surface layer of core and extra mesoporous cavities are introduced for substrate reservation. When applied for solvent-free epoxidation of methyl oleate (MO) with H2O2, TS@PMO exhibits remarkably boosted catalytic activity (X = 90.2%) and epoxide selectivity (S = 70.2%), overwhelming the unmodified titanosilicate (X = 63.7%, S = 49.2%) and Ti-containing organosilica (X = 39.8%, S = 25.0%). Such result benefits from an evidently enhanced interphase mass transfer and sufficiently accessible active Ti sites in TS@PMO. On the one hand, amphiphilic PMO shell can efficiently collect hydrophobic substrate and H2O2, while abundant mesopores in the shell offer open-path for them to access active sites in the core; on the other hand, an increased framework Ti (IV) density and their surface-enrichment in TS core greatly improve the utilization of active Ti sites. This study effectively makes up for the deficiencies of slow mass transfer and insufficient utilization of conventional titanosilicates in biphasic reactions, which paves a new avenue to exploit other hybrid catalysts for high-efficiency solvent-free catalysis.

In Vivo Dynamics and Phase State of Natural Lipid Droplets

All organisms store lipids as energy resource for metabolism. Such lipids are accumulated in the form of intracellular droplets. The structure of the lipid droplet is complex. The hydrophobic core represents a mix of un- and saturated triglycerides, enclosed by an amphiphilic shell of phospholipids with embedded proteins. Uncovering intrinsic biophysical properties of lipid droplets in living cells of various organisms is crucial for metabolism manipulation or reducing lipid storage. The type and organization of lipids affect their phase state and microscopic dynamics in the droplet. We characterized lipid droplets in the cells of fresh human and porcine subcutaneous fat tissues, as well as yeast cells using quasi-elastic neutron scattering, probing the molecular motions in a time scale of 6-400 picoseconds and a length scale of 3-20 Angstroms. The detected two-component dynamics in the droplet is associated with lipid unrestricted diffusion (D ∼ 0.006 A2/ps) and motions of its hydrocarbon chains (D ∼ 0.2 A2/ps) in a restricted volume (5-12 A). The dynamics of lipids is significantly reduced below 305 K and 266 K in porcine and human tissues, respectively, due to a first-order phase transition of lipids from fluid to gel (similar to synthetic lipid bilayer). The lipid phase change in human tissue is confirmed and enhanced at applied pressure of 90 bars. However, lipid droplets in the yeast cells remain in a fluid-like state within range of 280-310 K. We believe that phase behavior of lipid droplets is different in the cells of tissues and microorganism due to lipid composition, which was investigated by mass spectrometry. Lipid packing in the droplet is tight in the tissues, having mostly saturated lipids, and loose in the yeast droplet, having equal proportions of un- and saturated lipids.

Sequential synthesis of a magnetic nano-adsorbent: How the first step identifies the final product

Three types of super paramagnetic core-shell nanoparticles have creatively been synthesized via three basic substances, Fe2+/Fe3+, methacrylic acid (MAA), and 2,2′-azobisisobutyronitrile (AIBN). It has been demonstrated that the order of addition of starting materials determines the type of products. Methacrylic acid coated magnetic nanoparticles (Fe3O4@MAA) with abundant double bonds on the surface, poly methacrylic acid coated magnetic nano particles (Fe3O4@PMAA) having plenty of surface carboxylic groups, and amphiphilic shell of methacrylic acid polymer on magnetic nano particles core (Fe3O4@AMPH) having both carboxyl and alkyl groups on the surface were prepared in three, separate one-pot, sequential synthesis. At first, the resultant magnetic nanoparticles (MNPs) were characterized by transmission electron microscopy (TEM), dynamic light scattering, X-ray spectroscopy, Fourier transform infrared spectroscopy (FTIR) and thermal analysis. Then, the colloidal stability of the synthesized particles was investigated in several common solvents such as water, 1-propanol, chloroform, and edible oil. Finally, the application of each nanoparticle was discussed. It was found that Fe3O4@MAA can be successfully applied as a core in polymerization procedure. Fe3O4@PMAA performed well in nickel uptake and can therefore be used as magnetic solid sorbent in nickel pre-concentration and remediation. Fe3O4@AMPH was well dispersed in oil, suggesting that it can be successfully used as a good extractor in dispersive solid phase pre-concentration and cleanup of both hydrophilic and hydrophobic compounds in heated edible oil samples.

Structural Effects of High Hydrostatic Pressure on Human Low Density Lipoprotein Revealed by Small Angle X-ray and Neutron Scattering

Low-density lipoprotein (LDL) is the principal cholesterol transporter in the human blood circulation. The quasi-spherical LDL particles (∼20 nm) are made up of a complex combination of various lipids and a large single amphipathic protein moiety, named apolipoprotein B-100. LDL has a hydrophobic core and an amphiphilic shell. Each particle has a specific phase transition temperature (Tm) corresponding to the melting of the core lipids from an ordered liquid crystalline to a disordered fluid phase.The structural impact of high hydrostatic pressure (HHP) was studied with different types of LDL (native, oxidized and triglyceride rich) with SANS (PSI, Switzerland) and SAXS (Elettra, Italy). The HHP ranged from 50 to 3000 bar. Temperature points were chosen below, on and above Tm.The pair distance distribution functions p(r) of the SAS curves revealed pressure dependent changes of the particle structure seen in the low q-region (∼0.25 nm−1), also reflected by a decrease of Radii of Gyration (Rg) with increasing pressure.Especially the p(r) functions from the SAXS data do not only show an overall particle change but also a highly pressure sensitive inner organization. A triple-peak feature indicating the lamellar lipid organization below Tm was induced by raising the pressure up to 3000 bar. These pressure sensitive lipid layers were observed by scattering intensity changes in SAXS curves at q=1.7 nm−1.The shape alterations could be evidenced by fitting an ellipsoidal model to the SANS curves resulting in a decrease of the ellipsoidal radii under pressure. A new LDL model considering the cross-sectional electron density profile is developed and applied to the SAS data to get a more detailed insight into pressure dependent behavior.

WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are polymerizable under influence of ionizing radiation and are a promising design concept within the development of a novel non-invasive in-vivo radiation dosimeter for external beam radiation therapy. This work was funded by the Research Foundation - Flanders (FWO).

PEG-detachable lipid–polymer hybrid nanoparticle for delivery of chemotherapy drugs to cancer cells

The experiment aimed to increase the drug-delivery efficiency of poly-lactic-co-glycolic acid (PLGA) nanoparticles. Lipid-polymer hybrid nanoparticles (LPNs-1) were prepared using PLGA as a hydrophobic core and FA-PEG-hyd-DSPE as an amphiphilic shell. Uniform and spherical nanoparticles with an average size of 185 nm were obtained using the emulsification solvent evaporation method. The results indicated that LPNs-1 showed higher drug loading compared with naked PLGA nanoparticles (NNPs). Drug release from LPNs-1 was faster in an acidic environment than in a neutral environment. LPNs-1 showed higher cytotoxicity on KB cells, A549 cells, MDA-MB-231 cells, and MDA-MB-231/ADR cells compared with free doxorubicin (DOX) and NNPs. The results also showed that, compared with free DOX and NNPs, LPNs-1 delivered more DOX to the nuclear of KB cells and MDA-MB-231/ADR cells. LPNs-1 induced apoptosis in KB cells and MDA-MB-231/ADR cells in a dose-dependent manner. The above data indicated that DOX-loaded LPNs-1 could kill not only normal tumor cells but also drug-resistant tumor cells. These results indicated that modification of PLGA nanoparticles with FA-PEG-hyd-DSPE could considerably increase the drug-delivery efficiency and LPNs-1 had potential in the delivery of chemotherapeutic agents in the treatment of cancer.

Amphiphilic nanoparticles repress macrophage atherogenesis: novel core/shell designs for scavenger receptor targeting and down-regulation.

Atherosclerosis, an inflammatory lipid-rich plaque disease is perpetuated by the unregulated scavenger-receptor-mediated uptake of oxidized lipoproteins (oxLDL) in macrophages. Current treatments lack the ability to directly inhibit oxLDL accumulation and foam cell conversion within diseased arteries. In this work, we harness nanotechnology to design and fabricate a new class of nanoparticles (NPs) based on hydrophobic mucic acid cores and amphiphilic shells with the ability to inhibit the uncontrolled uptake of modified lipids in human macrophages. Our results indicate that tailored NP core and shell formulations repress oxLDL internalization via dual complementary mechanisms. Specifically, the most atheroprotective molecules in the NP cores competitively reduced NP-mediated uptake to scavenger receptor A (SRA) and also down-regulated the surface expression of SRA and CD36. Thus, nanoparticles can be designed to switch activated, lipid-scavenging macrophages to antiatherogenic phenotypes, which could be the basis for future antiatherosclerotic therapeutics.

Diffusion of guest molecules within sensitive core–shell microgel carriers

The diffusion of payloads within core–shell carrier particles is of major relevance for drug-delivery applications. We use spatially resolved two-focus fluorescence correlation spectroscopy to quantify the diffusivity of different dextran molecules and colloids within carrier particles composed of a temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) shell that surrounds a temperature-insensitive polyacrylamide core. The deswelling of the shell that occurs upon heating above the lower critical solution temperature of PNIPAM slightly slows down the diffusion of these tracer oligomers near the core–shell interface. By contrast, the mobility of the tracers inside the core is not affected by deswelling of the shell. This finding assures absence of artifacts such as adsorption of the guests to the amphiphilic shell polymer, supporting the utility of these microgel carriers in encapsulation and controlled release applications.

Efficacy of Amphiphilic Core-Shell Nanostructures Encapsulating Gentamicin in an In Vitro Salmonella and Listeria Intracellular Infection Model

Core-shell nanostructures with nonionic amphiphilic shells and ionic cores encapsulating gentamicin were designed for therapy against intracellular pathogens, including Salmonella and Listeria. Flow cytometry and confocal microscopy showed that their uptake into J774A.1 macrophages proceeded mainly by fluid-phase endocytosis and clathrin-mediated pathways. The nanostructures were nontoxic in vitro at doses of 50 to 250 microg/ml, and they significantly reduced the amounts of intracellular Salmonella (0.53 log) and Listeria (3.16 log), thereby suggesting effective transport into the cells.

Stimuli-Responsive Amphiphilic Shells of Kinetically Frozen Polymeric Micelles in Aqueous Media: Monte Carlo Simulations and Comparison to Self-Consistent Field Calculations

The behavior of amphiphilic shells of micelles with kinetically frozen hydrophobic cores in aqueous solutions was studied by Monte Carlo (MC) simulations. The calculations emulate the behavior of water-soluble shell-forming chains containing a relatively low fraction of strongly hydrophobic units, which are arranged in either sequences or are distributed uniformly in shell-forming chains. The analysis of concentration profiles of individual species reveals strong segregation and important self-organization of hydrophobic units in the shell. In this paper, we present new MC data. Further, we compare MC and self-consistent field (SCF) results and analyze possible sources of differences. The study shows that the SCF approach is applicable for studied systems, but an unambiguous interpretation of SCF data requires additional information. MC simulations yield detailed and self-explanatory characterization of the shell structure, but they are very time-consuming. The angularly averaged results of both techniques compare reasonably well at the semiquantitative level, but SCF overestimates the pH effects in annealed polyelectrolyte systems. A combination of both methods increases the impact of the study.

Grafting poly(t‐butyl acrylate) to poly(allylamine) by inverse microemulsion radical polymerization: From comb‐polymer to amphiphilic shell crosslinked polymer nanocapsule

AbstractAn interfacial grafting radical polymerization method for amphiphilic comb copolymer and shell crosslinked polymer nanocapsules was reported. Macropolyradicals on a water soluble long chain polyamine were generated with hydrogen peroxide in the water phase and subsequent grafting radical polymerization of a vinylic monomer at the water/oil interface proceeded at 65°C. In the presence of a crosslinker, the resulting graft copolymer formed a defined core‐shell structure with hydrophilic aqueous core functionalized by the polyamine and a hydrophobic crosslinked polymer shell. The structure of the core‐shell material was characterized by NMR, FTIR, DSC, TGA, SEM, TEM, and the mechanism of the graft polymerization is proposed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1905–1911, 2007

Langmuir−Blodgett Monolayers of Gold Nanoparticles with Amphiphilic Shells from V-Shaped Binary Polymer Arms

Gold nanoparticles functionalized with amphiphilic polybutadiene-poly(ethylene glycol) (PB-PEG) V-shaped arms formed stable Langmuir monolayers at the air-water and the air-solid interfaces. At these interfaces, the binary arms vertically segregated into a dense polymer corona, which surrounded the gold nanoparticles, preventing their large-scale agglomeration and keeping individual nanoparticles well-separated from each other and forming flattened, pancake nanostructures. The presence of both PEG and PB chains in the close proximity to the gold core was confirmed by surface enhanced Raman spectroscopy, whereas the AFM phase contrast images revealed the presence of 2 nm gold cores surrounded by the polymer shell with the diameter of 11 nm. We suggest that the amphiphilic shell drives their spontaneous organization into discrete 2D pancake-like hybrid structures that measured up to 10 microm in diameter and had a high packing density of gold clusters.