Interaction of Ras Binding Domain (RBD) by chemotherapeutic zinc oxide nanoparticles: Progress towards RAS pathway protein interference.

Zinc oxide (ZnO) NP is considered as a nanoscale chemotherapeutic. Thus, the drug delivery of this inorganic NP is of considerable importance. Ras mutations are common in cancer and the activation of this signaling pathway is a hallmark in carcinoma, melanoma and many other aggressive malignancies.

Structural Determinants of the Dopamine Transporter Regulation Mediated by G Proteins.

Dopamine clearance in the brain is controlled by the dopamine transporter (DAT), a protein residing in the plasma membrane, which drives reuptake of extracellular dopamine into presynaptic neurons. Studies have revealed that the βγ subunits of heterotrimeric G proteins modulate DAT function through a physical association with the C-terminal region of the transporter. Regulation of neurotransmitter transporters by Gβγ subunits is unprecedented in the literature; therefore, it is interesting to investigate the structural details of this particular protein-protein interaction.

Surface functionalization strategies of extracellular vesicles.

Extracellular vesicles (EVs) are lipid-protein bilayer vesicular constructs secreted to the extracellular spaces by cells. All cells secrete EVs as a regular biological process that appears to be conserved throughout the evolution. Owing to the rich molecular cargo of EVs with specific lipid and protein content and documented role in cellular communication, EVs have been exploited as a versatile agent in the biomedical arena, including as diagnostic, drug delivery, immunomodulatory, and therapeutic agents.

Strategic reconstruction of macrophage-derived extracellular vesicles as a magnetic resonance imaging contrast agent.

A contrast agent (CA) in magnetic resonance imaging (MRI) is now an essential add-on to obtain high-quality contrast-enhanced anatomical images for disease diagnosis and monitoring the treatment response. However, the rapid elimination of CAs by the immune system and excretion by the renal route has limited its application. As a result, the CA dose for effective contrast is ever-increasing, resulting in toxic side effects such as gadolinium (Gd) related nephrogenic systemic fibrosis (NSF) toxicity.

Using Naturally Occurring Bioluminescent Enzymes to Track Specific Cell Populations.

Luminol-based bioluminescence imaging allows noninvasive tracking of oxidatively active cells such as neutrophils. Luminol is given intravenously or intraperitoneally, followed by bioluminescence imaging at 425 nm. Here we describe a method for tracking neutrophil extravasation into an inflammatory site, especially focusing on mammary carcinoma.

Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach.

Numerous studies have engineered nanoparticles with different physicochemical properties to enhance the delivery efficiency to solid tumors, yet the mean and median delivery efficiencies are only 1.48% and 0.70% of the injected dose (%ID), respectively, according to a study using a nonphysiologically based modeling approach based on published data from 2005 to 2015.

pH-responsive cationic liposome for endosomal escape mediated drug delivery.

Endosomal degradation of the nanoparticle is one of the major biological barriers associated with the drug delivery system. Nanoparticles are internalized in the cell via different endocytosis pathways, where they are first delivered to early endosomes which mature to the late endosome and to the lysosome. During this journey, NP encounters a harsh chemical environment resulting in the degradation of NP and its content.

Integration of gadolinium in nanostructure for contrast enhanced-magnetic resonance imaging.

Magnetic resonance imaging (MRI) is a routinely used imaging technique in medical diagnostics, which is further enhanced with the use of contrast agents (CAs). The most commonly used CAs are gadolinium-based contrast agents (GBCAs), in which gadolinium (Gd) is chelated with organic chelating agents (linear or cyclic). However, the use of GBCA is related to toxic side effect due to the release of free Gd ions from the chelating agents.

Comparing the effects of physiologically-based metal oxide nanoparticles on ribonucleic acid and RAS/RBD-targeted triplex and aptamer interactions.

Physiological metals such as zinc, magnesium, and nickel facilitate nucleic acid and protein interactions and stability. In the nanoscale, the impact these have on nucleic acid structure-function is very poorly understood and was investigated here. Nanoparticles' (NP) RNA precipitation efficiency was in the order; NiO > MgO > ZnO > CaO > CaCO>Cu.

A Structural Model of the Inactivation Gate of Voltage-Activated Potassium Channels.

After opening, the Shaker voltage-gated potassium (K) channel rapidly inactivates when one of its four N-termini enters and occludes the channel pore. Although it is known that the tip of the N-terminus reaches deep into the central cavity, the conformation adopted by this domain during inactivation and the nature of its interactions with the rest of the channel remain unclear. Here, we use molecular dynamics simulations coupled with electrophysiology experiments to reveal the atomic-scale mechanisms of inactivation.

Impact of Gold Nanoparticles on Testosterone Metabolism in Human Liver Microsomes.

Gold nanoparticle (AuNP)-protein corona complexes can alter cytochrome P450 (CYP)-mediated testosterone (TST) metabolism by altering their physicochemical properties. We investigated the impact of NP size, surface chemistry, and protein corona in TST metabolism in pooled human liver microsomes (pHLM) employing 40 and 80 nm AuNP functionalized with branched polyethylenimine (BPEI), lipoic acid (LA), and polyethylene glycol (PEG) as well as human plasma protein corona (PC). Individual variation in AuNP-mediated TST metabolism was also characterized among single donor HLM that contained different levels of CYP activities.

Biodistribution of gadolinium- and near infrared-labeled human umbilical cord mesenchymal stromal cell-derived exosomes in tumor bearing mice.

We speculate that exosomes derived from human umbilical cord mesenchymal stromal cells (HUC-MSCs) will accumulate within tumors and have the potential for both tumor location or drug delivery. : To determine proof of concept, HUC-MSC exosomes were labeled with an MRI contrast agent, gadolinium, or a near infrared dye. Exosome accumulation within ectopic osteosarcoma tumor-bearing mice was determined by 14.

Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery.

Extracellular vesicles (EVs) are phospholipid and protein constructs which are continuously secreted by cells in the form of smaller (30-200 nm) and larger (micron size) particles. While all of these vesicles are called as EVs, the smaller size are normally called as exosomes. Small EVs (sEVs) have now been explored as a potential candidate in therapeutics delivery owing to their endogenous functionality, intrinsic targeting property, and ability to cooperate with a host defense mechanism.

Affordable Membrane Permeability Calculations: Permeation of Short-Chain Alcohols through Pure-Lipid Bilayers and a Mammalian Cell Membrane.

Determination of membrane permeability to small molecules from first-principles represents a promising approach for screening lead compounds according to their permeation properties upstream in the drug discovery process and prior to their synthesis. Theoretical investigation of permeation events requires, at its core, a molecular model of the membrane, and the choice of this model impacts not only the predicted permeability but also its relation to the experimental measurements commonly performed in pharmaceutical settings with a variety of cell lines capable of mimicking intestinal passive permeation. Homogeneous single-lipid bilayers have traditionally been utilized in computer simulations of membrane permeability predictions due to the ease of sampling all the relevant configurations, as well as the availability of parameters for a range of components of the biological membrane.

Interaction of Surface Energy Components between Solid and Liquid on Wettability, and Its Application to Textile Anti-Wetting Finish.

With various options of anti-wetting finish methods, this study intends to provide basic information that can be applied in selecting a relevant anti-wetting chemical to grant protection from spreading of liquids with different surface energy profiles. With such an aim, the anti-wetting effectiveness of fluorinated coating and silane coating was investigated for liquids having different surface energy components, water (WA), methylene iodide (MI) and formamide (FA). The wetting thermodynamics was experimentally investigated by analyzing dispersive and polar component surface energies of solids and liquids.

Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery.

In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic--glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo skin insertion tests. The compression test demonstrated that no noticeable layer separation occurred, indicating good adhesion between PLGA and PVP layers.

Thermodynamics of Adsorption on Graphenic Surfaces from Aqueous Solution.

Adsorption of organic molecules from aqueous solution to the surface of carbon nanotubes or graphene is an important process in many applications of these materials. Here we use molecular dynamics simulation, supplemented by analytical chemistry, to explore in detail the adsorption thermodynamics of a diverse set of aromatic compounds on graphenic materials, elucidating the effects of the solvent, surface coverage, surface curvature, defects, and functionalization by hydroxy groups. We decompose the adsorption free energies into entropic and enthalpic components and find that different classes of compounds-such as phenols, benzoates, and alkylbenzenes-can easily be distinguished by the relative contributions of entropy and enthalpy to their adsorption free energies.

Biomimetic surface modification of discoidal polymeric particles.

The rationale for the design of drug delivery nanoparticles is traditionally based on co-solvent self-assembly following bottom-up approaches or in combination with top-down approaches leading to tailored physiochemical properties to regulate biological responses. However, the optimal design and control of material properties to achieve specific biological responses remain the central challenge in drug delivery research. Considering this goal, we herein designed discoidal polymeric particles (DPPs) whose surfaces are re-engineered with isolated red blood cell (RBC) membranes to tailor their pharmacokinetics.

Toxicity assessment of six titanium dioxide nanoparticles in human epidermal keratinocytes.

Purpose: The aim of this study was to evaluate and compare the toxicity of six different types of titanium dioxide (TiO) nanoparticles (NP) on human epidermal keratinocytes (HEK).

Materials And Methods: Six TiO NP (A (10 nm), A*(32 nm), B (27.5 nm), C (200 nm), C*(30-40 nm), and D*(200-400 nm)) were suspended in water or culture medium and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS).

Influence of shell compositions of solution blown PVP/PCL core-shell fibers on drug release and cell growth.

Developing a facile means of controlling drug release is of utmost interest in drug delivery systems. In this study, core-shell structured nanofibers containing a water-soluble porogen were fabricated solution blow spinning, to be used as drug-loaded bioactive tissue scaffolds. Hydrophilic polyvinylpyrrolidone (PVP) and hydrophobic poly(ε-caprolactone) (PCL) were chosen to produce the core and the shell compartments of the fiber, respectively.

Assessment of Gold Nanoparticles-Inhibited Cytochrome P450 3A4 Activity and Molecular Mechanisms Underlying Its Cellular Toxicity in Human Hepatocellular Carcinoma Cell Line C3A.

Interactions of the 40 and 80 nm gold nanoparticles (AuNP) functionalized with cationic branched polyethylenimine (BPEI), anionic lipoic acid (LA), or neutral polyethylene glycol (PEG) with human hepatocellular carcinoma (HCC) cell line C3A have been investigated in the absence and presence of human plasma protein corona (PC). All bare (no PC) AuNP besides 80 nm LA-AuNP were cytotoxic to C3A but PC attenuated their cytotoxicities. Time-dependent cellular uptake of AuNP increased besides 40 nm BPEI-AuNP but PC suppressed their uptakes besides 80 nm PEG-AuNP.

Comparative functional dynamics studies on the enzyme nano-bio interface.

Introduction: Biomedical applications of nanoparticles (NPs) as enzyme inhibitors have recently come to light. Oxides of metals native to the physiological environment (eg, Fe, Zn, Mg, etc.) are of particular interest-especially the functional consequences of their enzyme interaction.

Insertion-responsive microneedles for rapid intradermal delivery of canine influenza vaccine.

In this study, we present transcutaneous influenza vaccination using a novel tip-separable microneedle system called insertion-responsive microneedles (IRMNs). IRMNs are composed of dissolvable hyaluronic acid (HA) tips and biocompatible polycaprolactone (PCL) bases, the tip of which is instantly separated from the base during microneedle insertion and retraction. Vaccine antigens derived from canine influenza virus (A/canine/VC378/2012; H3N2) were successfully coated on HA tips by rapidly freezing the tips prior to coating.

Experimental and Computational Characterization of the Interaction between Gold Nanoparticles and Polyamidoamine Dendrimers.

Dendrimers provide a means to control the synthesis of gold nanoparticles and stabilize their suspensions. However, design of improved dendrimers for this application is hindered by a lack of understanding how the dendrimers and synthesis conditions determine nanoparticle morphology and suspension stability. In the present work, we evaluate the effect of polyamidoamine (PAMAM) dendrimers terminated with different functional groups (-OH or -NH) and different synthesis conditions on the morphology of the resulting gold nanoparticles and their stability in solution.