Photothermal induction of pyroptosis in malignant glioma spheroids using (16-mercaptohexadecyl)trimethylammonium bromide-modified cationic gold nanorods.

Plasmonic photothermal therapy (PPTT) employing plasmonic gold nanorods (GNRs) presents a potent strategy for eradication of tumors including aggressive brain gliomas. Despite its promise, there is a pressing need for a more comprehensive evaluation of PPTT using sophisticated in vitro models that closely resemble tumor tissues, thereby facilitating the elucidation of therapeutic mechanisms. In this study, we exposed 3D glioma spheroids (tumoroids) to (16-mercaptohexadecyl)trimethylammonium bromide-functionalized gold nanorods (MTAB-GNRs) and a near-infrared (NIR) laser.

Long-Term Accumulation, Biological Effects and Toxicity of BSA-Coated Gold Nanoparticles in the Mouse Liver, Spleen, and Kidneys.

Introduction: Gold nanoparticles are promising candidates as vehicles for drug delivery systems and could be developed into effective anticancer treatments. However, concerns about their safety need to be identified, addressed, and satisfactorily answered. Although gold nanoparticles are considered biocompatible and nontoxic, most of the toxicology evidence originates from in vitro studies, which may not reflect the responses in complex living organisms.

The Effect of Chemical Structure of OEG Ligand Shells with Quaternary Ammonium Moiety on the Colloidal Stabilization, Cellular Uptake and Photothermal Stability of Gold Nanorods.

Purpose: Plasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain - (16-mercaptohexadecyl)trimethylammonium bromide (MTAB).

Gold Film over SiO Nanospheres-New Thermally Resistant Substrates for Surface-Enhanced Raman Scattering (SERS) Spectroscopy.

Surface-enhanced Raman scattering (SERS) sensors are constructed from metallic plasmonic nanostructures providing high sensitivity and spectral reproducibility. In many cases, irradiation of the SERS substrate by the laser beam leads to an increase of the local temperature and consequently to thermal degradation of metallic nanostructure itself and/or adsorbed analyte. We report here a "bottom-up" technique to fabricate new thermally resistant gold "film over nanosphere" (FON) substrates for SERS.

Biological safety and tissue distribution of (16-mercaptohexadecyl)trimethylammonium bromide-modified cationic gold nanorods.

The exceptionally high cellular uptake of gold nanorods (GNRs) bearing cationic surfactants makes them a promising tool for biomedical applications. Given the known specific toxic and stress effects of some preparations of cationic nanoparticles, the purpose of this study was to evaluate, in an in vitro and in vivo in mouse, the potential harmful effects of GNRs coated with (16-mercaptohexadecyl)trimethylammonium bromide (GNRs). Interestingly, even after cellular accumulation of high amounts of GNRs sufficient for induction of photothermal effect, no genotoxicity (even after longer-term accumulation), induction of autophagy, destabilization of lysosomes (dominant organelles of their cellular destination), alterations of actin cytoskeleton, or in cell migration could be detected in vitro.

Two-Step Mechanism of Cellular Uptake of Cationic Gold Nanoparticles Modified by (16-Mercaptohexadecyl)trimethylammonium Bromide.

Cationic colloidal gold nanorods (GNRs) have a great potential as a theranostic tool for diverse medical applications. GNRs' properties such as cellular internalization and stability are determined by physicochemical characteristics of their surface coating. GNRs modified by (16-mercaptohexadecyl)trimethylammonium bromide (MTAB), GNRs, show excellent cellular uptake.

Enhanced photoemission from laser-excited plasmonic nano-objects in periodic arrays.

The process of photoelectron emission from gold surfaces covered with nano-objects that are organized in the form of a periodic array is addressed in the short laser pulse regime ([Formula: see text] fs) at moderate intensities [Formula: see text] W cm(-2) and for various laser wavelengths. The emission spectrum from a gold single crystal measured under the same conditions is used for reference. The comparison of the photo-emission yield and the energy of the ejected electrons with their counterparts from the (more simple) reference system shows that the periodic conditions imposed on the target surface drastically enhance both quantities.

Electron Acceleration by Relativistic Surface Plasmons in Laser-Grating Interaction.

The generation of energetic electron bunches by the interaction of a short, ultraintense (I>10(19)  W/cm(2)) laser pulse with "grating" targets has been investigated in a regime of ultrahigh pulse-to-prepulse contrast (10(12)). For incidence angles close to the resonant condition for surface plasmon excitation, a strong electron emission was observed within a narrow cone along the target surface, with energy spectra peaking at 5-8 MeV and total charge of ∼100  pC. Both the energy and the number of emitted electrons were strongly enhanced with respect to simple flat targets.

Quantitative SERS analysis of azorubine (E 122) in sweet drinks.

Considering both the potential effects on human health and the need for knowledge of food composition, quantitative detection of synthetic dyes in foodstuffs and beverages is an important issue. For the first time, we report a fast quantitative analysis of the food and drink colorant azorubine (E 122) in different types of beverages using surface-enhanced Raman scattering (SERS) without any sample preparation. Seven commercially available sweet drinks (including two negative controls) with high levels of complexity (sugar/artificial sweetener, ethanol content, etc.

In situ WetSTEM observation of gold nanorod self-assembly dynamics in a drying colloidal droplet.

Direct in situ visualization of nanoparticles in a liquid is an important challenge of modern electron microscopy. The increasing significance of bottom-up methods in nanotechnology requires a direct method to observe nanoparticle interactions in a liquid as the counterpart to the ex situ electron microscopy and indirect scattering and spectroscopy methods. Especially, the self-assembly of anisometric nanoparticles represents a difficult task, and the requirement to trace the route and orientation of an individual nanoparticle is of highest importance.

Evidence of resonant surface-wave excitation in the relativistic regime through measurements of proton acceleration from grating targets.

The interaction of laser pulses with thin grating targets, having a periodic groove at the irradiated surface, is experimentally investigated. Ultrahigh contrast (~10(12)) pulses allow us to demonstrate an enhanced laser-target coupling for the first time in the relativistic regime of ultrahigh intensity >10(19) W/cm(2). A maximum increase by a factor of 2.

Laser-driven proton acceleration enhancement by nanostructured foils.

Nanostructured thin plastic foils have been used to enhance the mechanism of laser-driven proton beam acceleration. In particular, the presence of a monolayer of polystyrene nanospheres on the target front side has drastically enhanced the absorption of the incident 100 TW laser beam, leading to a consequent increase in the maximum proton energy and beam charge. The cutoff energy increased by about 60% for the optimal spheres' diameter of 535 nm in comparison to the planar foil.

The effect of oxime reactivators on muscarinic receptors: functional and binding examinations.

The antidotal treatment of organophosphorus poisoning is still a problematic issue since no versatile antidote has been developed yet. In our study, we focused on an interesting property, which does not relate to the reactivation of inhibited acetylcholinesterase (AChE) of some oximes, but refers to their anti-muscarinic effects which may contribute considerably to their treatment efficacy. One standard reactivator (HI-6) and two new compounds (K027 and K203) have been investigated for their antimuscarinic properties.

Novel acetylcholinesterase reactivator K112 and its cholinergic properties.

The oxime reactivator K112 is a member of the new group of xylene linker-containing AChE reactivators. Its cholinergic properties could be of importance at OP poisoning and are not related to the AChE reactivation that has been studied. It has been found that, despite of reactivating potency, this compound has additional effects.

Interaction of nerve agent antidotes with cholinergic systems.

The poisoning with organophosphorus compounds represents a life threatening danger especially in the time of terroristic menace. No universal antidote has been developed yet and other therapeutic approaches not related to reactivation of acetylcholinesterase are being investigated. This review describes the main features of the cholinergic system, cholinergic receptors, cholinesterases and their inhibitors.

Methylacridinium and its cholinergic properties.

10-Methylacridinium iodide (methylacridinium; MA) is an inhibitor of cholinesterases. Inhibitors of acetylcholinesterase (AChE) are used in the treatment of myasthenia gravis, Alzheimer's disease, and in the prophylaxis of poisoning with organophosphates. Using spectrophotometric Ellman's method at 436 nm and commercial enzymes we found that MA inhibits AChE by binding with relatively high potency to the peripheral anionic site (IC(50) = 1.

Synthesis and analgesic activity of some quinazoline analogs of anpirtoline.

New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, quinazoline, 7-chloroquinoline, and 7-chloroquinazoline nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 4e-4g, and 4l are at least comparable to that of clinically used drugs flupirtine and tramadol under the same conditions.

Synthesis and analgesic activity of some side-chain modified anpirtoline derivatives.

New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.

Synthesis and analgesic activity of some condensed analogs of anpirtoline.

New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, isoquinoline, quinazoline, and phthalazine nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 7d, 8b, 8c, and 8e are at least comparable to that of the clinically used drugs flupirtine and tramadol under the same conditions.

Synthesis and analgesic activity of some deaza derivatives of anpirtoline.

New deaza derivatives of anpirtoline have been synthesized by three different methods. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied.

Positive allosteric action of eburnamonine on cardiac muscarinic acetylcholine receptors.

It was discovered recently that alcuronium and strychnine (which is a precursor of alcuronium) allosterically increase the affinity of cardiac muscarinic receptors for the antagonist, N-methylscopolamine. We have now investigated the effects of l-eburnamonine and vincamine, which are both closely related to strychnine. In experiments on rat heart atria, l-eburnamonine was found to increase the binding of [3H]N-methylscopolamine with Ehlert's cooperativity coefficient alpha = 0.

Competition between positive and negative allosteric effectors on muscarinic receptors.

Alcuronium allosterically increases the affinity of cardiac muscarinic receptors for methyl-N-scopolamine (NMS), whereas gallamine has the opposite effect. We discovered that strychnine also increases the affinity of muscarinic receptors in rat heart atria for NMS. It is not known whether the positive and the negative allosteric effectors bind to the same binding site.

Allosteric modulation of muscarinic acetylcholine receptors.

Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of allosteric control of muscarinic receptors have been obtained recently in investigations of the allosteric effects of neuromuscular blockers, and competition between ligands for the allosteric binding site has now been demonstrated.

Mechanisms of steric and cooperative actions of alcuronium on cardiac muscarinic acetylcholine receptors.

Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuronium concentration-dependently slowed the association of [3H]NMS with receptors and the dissociation of [3H]NMS from receptors so that, at high alcuronium concentrations, equilibrium binding could not be reached, even after 20 hr, without special precautions.