Membrane Fusion-Mediated Gold Nanoplating of Red Blood Cell: A Bioengineered CT-Contrast Agent.

Red blood cells (RBCs) are the natural resident of the vascular lumen, therefore delivery of any agents within the vascular lumen could benefit by unique natural transporting features of RBCs. RBCs continuously circulate for ∼100 days before being sequestered in the spleen, they only extravasate at sites of vascular hemorrhage. Taking advantages of these features, we engineered RBC as a carrier in order to design a unique delivery system capable of delivering X-ray computed tomography (CT) contrast agents, gold nanoparticles (AuNPs), thereby acting as CT-contrast agent.

Protein corona modulation of hepatocyte uptake and molecular mechanisms of gold nanoparticle toxicity.

Protein corona formation over gold nanoparticles (AuNP) can modulate cellular responses by altering AuNP physicochemical properties. The liver plays an essential role in metabolism, detoxification and elimination of xenobiotics and drugs as well as circulating NP clearance. We investigated human hepatic uptake of 40 and 80 nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human serum albumin (HSA) coronas.

Mechanisms of cell uptake, inflammatory potential and protein corona effects with gold nanoparticles.

Aim: To assess inflammation, cellular uptake and endocytic mechanisms of gold nanoparticles (AuNP) in human epidermal keratinocytes with and without a protein corona.

Materials & Methods: Human epidermal keratinocytes were exposed to 40 and 80 nm AuNP with lipoic acid, polyethylene glycol (PEG) and branched polyethyleneimine (BPEI) coatings with and without a protein corona up to 48 h. Inhibitors were selected to characterize endocytosis.

Biological and environmental surface interactions of nanomaterials: characterization, modeling, and prediction.

The understanding of nano-bio interactions is deemed essential in the design, application, and safe handling of nanomaterials. Proper characterization of the intrinsic physicochemical properties, including their size, surface charge, shape, and functionalization, is needed to consider the fate or impact of nanomaterials in biological and environmental systems. The characterizations of their interactions with surrounding chemical species are often hindered by the complexity of biological or environmental systems, and the drastically different surface physicochemical properties among a large population of nanomaterials.

Engineered Nanomedicine with Alendronic Acid Corona Improves Targeting to Osteosarcoma.

We engineered nanomedicine with the stealth corona made up of densely packed bone seeking ligand, alendronic acid. In a typical nanoconstruct, alendronic acid is conjugated with hydrophilic head moiety of phospholipid that has an ability to self-assemble with hydrophobic polymeric core through its hydrophobic long carbon-chain. Proposed nanomedicine has three distinct compartments namely; poly(l-lactic-co-glycolic acid) polymeric core acting as a drug reservoir and skeleton of the nanoconstruct, phospholipid monolayer covers the core acting as a diffusion barrier, and a densely packed alendronic acid corona acting as a stabilizer and targeting moiety.

Subdiffusion in Membrane Permeation of Small Molecules.

Within the solubility-diffusion model of passive membrane permeation of small molecules, translocation of the permeant across the biological membrane is traditionally assumed to obey the Smoluchowski diffusion equation, which is germane for classical diffusion on an inhomogeneous free-energy and diffusivity landscape. This equation, however, cannot accommodate subdiffusive regimes, which have long been recognized in lipid bilayer dynamics, notably in the lateral diffusion of individual lipids. Through extensive biased and unbiased molecular dynamics simulations, we show that one-dimensional translocation of methanol across a pure lipid membrane remains subdiffusive on timescales approaching typical permeation times.

Biocorona Bound Gold Nanoparticles Augment Their Hematocompatibility Irrespective of Size or Surface Charge.

Despite colloidal gold nanoparticles (AuNP) being proposed for a multitude of biomedical applications, there is a lack of understanding on how the protein corona (PC) formation over AuNP influences its interaction with blood components. Herein, 40 and 80 nm AuNP with branched polyethylenimine, lipoic acid, and polyethylene glycol surface coatings were exposed to human plasma, and time-dependent evolution of the PC was evaluated using differential centrifugation sedimentation. Further, the impact of PC-AuNP interaction with human blood components was studied by evaluating red blood cell (RBC) aggregation, hemolysis, platelet activation and aggregation, prothrombin time, activated partial thromboplastin time, complement activation and cytokine release.

Intracellular imaging of quantum dots, gold, and iron oxide nanoparticles with associated endocytic pathways.

Metallic nanoparticles (NP) have been used for biomedical applications especially for imaging. Compared to nonmetallic NP, metallic NP provide high contrast images because of their optical light scattering, magnetic resonance, X-ray absorption, or other physicochemical properties. In this review, a series of in vitro imaging techniques for metallic NP will be introduced, meanwhile their strengths and weaknesses will be discussed.

Self-Assembly of Amphiphilic Dendrimers: The Role of Generation and Alkyl Chain Length in siRNA Interaction.

An ideal nucleic-acid transfection system should combine the physical and chemical characteristics of cationic lipids and linear polymers to decrease cytotoxicity and uptake limitations. Previous research described new types of carriers termed amphiphilic dendrimers (ADs), which are based on polyamidoamine dendrimers (PAMAM). These ADs display the cell membrane affinity advantage of lipids and preserve the high affinity for DNA possessed by cationic dendrimers.

Toward RNA nanoparticle vaccines: synergizing RNA and inorganic nanoparticles to achieve immunopotentiation.

Traditionally, vaccines have been composed of live attenuated or killed microorganisms. Alternatively, individual protein subunits or other molecular components of the microorganism can serve as the antigen and trigger an antibody response by the immune system. The immune system is a coordinated molecular and cellular response that works in concert to check the spread of infection.

Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels.

The molecular sensors that mediate temperature changes in living organisms are a large family of proteins known as thermosensitive transient receptor potential (TRP) ion channels. These membrane proteins are polymodal receptors that can be activated by cold or hot temperatures, depending on the channel subtype, voltage, and ligands. The stimuli sensors are allosterically coupled to a pore domain, increasing the probability of finding the channel in its ion conductive conformation.

Paramagnetic Gd(3+) labeled red blood cells for magnetic resonance angiography.

Despite significant advances in contrast enhanced-magnetic resonance angiography, the lack of truly blood-pool agents with long circulating property is limiting the clinical impact of this imaging technique. The terminal half-life for blood elimination of most small molecular weight gadolinium (Gd) based extracellular fluid agents is about 1.5 h when administered intravenously to subjects with normal renal function.

Development of hydrophobic surface substrates enabling reproducible drop-and-dry spectroscopic measurements.

We investigated several spectroscopic substrates with hydrophobic surfaces that were able to form reproducible droplets of aqueous samples for reliable high throughput drop-and-dry measurements. An amine-coated substrate, a polytetrafluoroethylene (PTFE) disk, and a perfluorooctyltrichlorosilane (FTS) coated substrate were prepared and initially evaluated for use in the determination of fat concentrations in milks using near-infrared (NIR) spectroscopy. Since the dried milk spots were not compositionally uniform due to the localization of components during sample drying, NIR spectra were collected by fully covering each spot to ensure a correct compositional representation of the sample.

Unique Boron Carbide Nanoparticle Nanobio Interface: Effects on Protein-RNA Interactions and 3-D Spheroid Metastatic Phenotype.

Aim: The effect of boron carbide (B4C) nanoparticles (NP) on protein-RNA complexes and metastatic phenotype of 3-D tumor spheroids was investigated.

Materials And Methods: Characterization was performed by transmission electron microscopy (TEM), zeta potential (ZP), 2-dimensional fluorescence difference spectroscopy (2-D FDS), gel electrophoresis, MTT, haemolysis and 3-D tumor spheroid assays.

Results: TEM showed NP were homogenous (≤50 nm) and spherical in shape.

Quantification of nanoparticle pesticide adsorption: computational approaches based on experimental data.

Quantitative analysis of the interactions between nanomaterials and environmental contamINANts, such as pesticides, in natural water systems and food residuals is crucial for the application of nanomaterials-based tools for the detection of the presence of toxic substances, monitoring pollution levels and environmental remediation. Previously, the Biological Surface Adsorption Index (BSAI) has demonstrated promising capabilities of interaction characterization and prediction based on experimental data from small organic molecules. In this article, the first attempt of the application of such quantitative measures toward environmental endpoints by analyzing the interactions of a selected group of nanomaterials with a variety of pesticides was made.

Simulation-Based Approaches for Determining Membrane Permeability of Small Compounds.

Predicting the rate of nonfacilitated permeation of solutes across lipid bilayers is important to drug design, toxicology, and signaling. These rates can be estimated using molecular dynamics simulations combined with the inhomogeneous solubility-diffusion model, which requires calculation of the potential of mean force and position-dependent diffusivity of the solute along the transmembrane axis. In this paper, we assess the efficiency and accuracy of several methods for the calculation of the permeability of a model DMPC bilayer to urea, benzoic acid, and codeine.

Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity.

The development of new strategies to renew and repair neuronal networks using neural plasticity induced by stem cell graft could enable new therapies to cure diseases that were considered lethal until now. In adequate microenvironment a neuronal progenitor must receive molecular signal of a specific cellular context to determine fate, differentiation, and location. TRPV1, a nonselective calcium channel, is expressed in neurogenic regions of the brain like the subgranular zone of the hippocampal dentate gyrus and the telencephalic subventricular zone, being valuable for neural differentiation and neural plasticity.

Intracellular delivery of molecules using microfabricated nanoneedle arrays.

Many bioactive molecules have intracellular targets, but have difficulty crossing the cell membrane to reach those targets. To address this difficulty, we fabricated arrays of nanoneedles to gently and simultaneously puncture 10(5) cells and thereby provide transient pathways for transport of molecules into the cells. The nanoneedles were microfabricated by etching silicon to create arrays of nanoneedles measuring 12 μm in height, tapering to a sharp tip less than 30 nm wide to facilitate puncture into cells and spaced 10 μm apart in order to have at least one nanoneedle puncture each cell in a confluent monolayer.

New Insights into Peptide-Silver Nanoparticle Interaction: Deciphering the Role of Cysteine and Lysine in the Peptide Sequence.

We studied the interaction of four new pentapeptides with spherical silver nanoparticles. Our findings indicate that the combination of the thiol in Cys and amines in Lys/Arg residues is critical to providing stable protection for the silver surface. Molecular simulation reveals the atomic scale interactions that underlie the observed stabilizing effect of these peptides, while yielding qualitative agreement with experiment for ranking the affinity of the four pentapeptides for the silver surface.

A computational framework for interspecies pharmacokinetics, exposure and toxicity assessment of gold nanoparticles.

Aim: To develop a comprehensive computational framework to simulate tissue distribution of gold nanoparticles (AuNP) across several species.

Materials & Methods: This framework was built on physiologically based pharmacokinetic modeling, calibrated and evaluated with multiple independent datasets.

Results: Rats and pigs seem to be more appropriate models than mice in animal-to-human extrapolation of AuNP pharmacokinetics and that the dose and age should be considered.

Multiple-Replica Strategies for Free-Energy Calculations in NAMD: Multiple-Walker Adaptive Biasing Force and Walker Selection Rules.

From the most powerful supercomputers to multicore desktops and laptops, parallel computing architectures have been in the mainstream for some time. However, numerical schemes for calculating free energies in molecular systems that directly leverage this hardware paradigm, usually taking the form of multiple-replica strategies, are just now on the cusp of becoming standard practice. Here, we present a modification of the popular molecular dynamics program NAMD that is envisioned to facilitate the use of powerful multiple-replica strategies to improve ergodic sampling for a specific class of free-energy methods known as adaptive biasing force.

Synthesis and Characterization of Biomimetic Hydroxyapatite Nanoconstruct Using Chemical Gradient across Lipid Bilayer.

In this study, we synthesized biomimetic hydroxyapatite nanoconstruct (nanosized hydroxyapatite, NHAp) using a double emulsion technique combined with a chemical gradient across a lipid bilayer for surface modification of a titanium (Ti) implant. The synthesized NHAp was characterized by dynamic light scattering, X-ray diffraction, transmission electron microscopy, and Fourier transform infrared (FTIR) spectroscopy, and it was further tested for its biocompatibility and in vitro proliferation efficacy using normal human osteoblasts (NHOst). The results showed that the synthesized NHAp had a hydrodynamic diameter of ∼200 nm with high aqueous stability.

Predicting Adsorption Affinities of Small Molecules on Carbon Nanotubes Using Molecular Dynamics Simulation.

Computational techniques have the potential to accelerate the design and optimization of nanomaterials for applications such as drug delivery and contaminant removal; however, the success of such techniques requires reliable models of nanomaterial surfaces as well as accurate descriptions of their interactions with relevant solutes. In the present work, we evaluate the ability of selected models of naked and hydroxylated carbon nanotubes to predict adsorption equilibrium constants for about 30 small aromatic compounds with a variety of functional groups. The equilibrium constants determined using molecular dynamics coupled with free-energy calculation techniques are directly compared to those derived from experimental measurements.

Soft Discoidal Polymeric Nanoconstructs Resist Macrophage Uptake and Enhance Vascular Targeting in Tumors.

Most nanoparticles for biomedical applications originate from the self-assembling of individual constituents through molecular interactions and possess limited geometry control and stability. Here, 1000 × 400 nm discoidal polymeric nanoconstructs (DPNs) are demonstrated by mixing hydrophobic and hydrophilic polymers with lipid chains and curing the resulting paste directly within silicon templates. By changing the paste composition, soft- and rigid-DPNs (s- and r-DPNs) are synthesized exhibiting the same geometry, a moderately negative surface electrostatic charge (-14 mV), and different mechanical stiffness (∼1.

Sonoporation at Small and Large Length Scales: Effect of Cavitation Bubble Collapse on Membranes.

Ultrasound has emerged as a promising means to effect controlled delivery of therapeutic agents through cell membranes. One possible mechanism that explains the enhanced permeability of lipid bilayers is the fast contraction of cavitation bubbles produced on the membrane surface, thereby generating large impulses, which, in turn, enhance the permeability of the bilayer to small molecules. In the present contribution, we investigate the collapse of bubbles of different diameters, using atomistic and coarse-grained molecular dynamics simulations to calculate the force exerted on the membrane.