Cysteamine Research Articles

Thiol‐Ene Coupling Reaction for Functionalization of Non‐Activated Alkenes: An Experimental Study on the Chemistry of the Methyl Oleate Amination

AbstractThis work investigates the functionalization of molecules with non‐activated internal double bonds via thiol‐ene coupling (TEC) reaction. A comprehensive study of the reaction between cysteamine hydrochloride (CAHC) and methyl oleate (MO) was carried out. A series of reactions were conducted under different operating conditions in order to assess their effect on conversion and selectivity. Different conditions were considered like the type of atmospheres and solvents, a portionwise addition of CAHC, reagents concentrations, and excess of CAHC. Maximum conversion and selectivity were reached under inert atmosphere, diluted conditions, ethanol as solvent, and the addition of CAHC at the beginning of the reaction with a molar ratio of CAHC/MO of 3/1. This provides an approach for analyzing more complex reaction systems.

Adsorption of l-Cysteine and Cysteamine on Zinc Oxide Nanoparticles.

The reaction of l-cysteine and cysteamine hydrochloride with zinc oxide nanoparticles (ZnO NPs), by stirring excess reactant with the NPs in ethanol, has been studied by thermal gravimetric analysis (TGA), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Raman spectroscopy. l-Cysteine adsorption occurs via the thiol functional group, and there is no evidence for bonding via the carboxylic acid or amine functionalities. However, Raman spectroscopy and XPS reveal some protonated thiol, suggesting unbound l-cysteine is also present, as confirmed by XRD that shows the presence of l-cysteine crystallites. In the case of cysteamine/ZnO, TGA indicates that a large fraction of the sample is organic, and Raman spectroscopy reveals a dramatic shift in the C-S stretch from 796 cm-1 for unreacted cysteamine to 837 cm-1 for the reacted cysteamine. It is postulated that the acidic and chelating nature of the reaction causes dissolution of some Zn2+ ions that form a Zn(II) coordination complex with cysteamine. These studies have implications for biomolecular applications in which ZnO nanoparticles are used for biosensors, bioimaging, and drug delivery.

Synthetic Control of Water-Stable Hybrid Perovskitoid Semiconductors.

Hybrid metal-halide perovskites and their derived materials have emerged as the next-generation semiconductors with a wide range of applications, including photovoltaics, light-emitting devices, and other optoelectronics. Over the past decade, numerous single-crystalline perovskite derivatives have been synthesized and developed. However, the synthetic methods for these derivatives mainly rely on acidic crystallization conditions. This approach leads to crystals comprising metal halide building blocks, which show problematic stability when directly exposed to water. In this study, a methodology is developed for synthesizing hybrid metal-halide compounds using lead iodide and the zwitterionic bifunctional molecule cysteamine (CYS), to form various perovskitoid structures under a broad pH range. Interestingly, the different pH conditions alter the coordination environment of lead halides, leading to lead-sulfide and lead-nitride covalent bond formation. This modification significantly enhances their stability when in direct contact with water, lasting for months. Photoluminescence measurements and first principal density functional theory (DFT) calculations reveal that the perovskitoids synthesized under basic and acidic pH conditions exhibit a direct bandgap nature, while those synthesized under neutral conditions display an indirect bandgap. This approach opens new avenues for manipulating synthetic methods to develop water-stable hybrid semiconductors suitable for a wide range of applications, such as solid-state light emitters.

Bioreceptors’ immobilization by hydrogen bonding interactions and differential pulse voltammetry for completely label-free electrochemical biosensors

Label-free electrochemical biosensors show great potential for the development of point-of-care devices (POCDs) for environmental and clinical applications. These sensors operate with shorter analysis times and are more economic than the labelled ones. Here, four completely label-free biosensors without electron transfer mediators were developed for hepatitis B virus (HBV) detection. The approach consisted in (i) the modification of gold surfaces with cysteamine (CT) or cysteine (CS) linkers, (ii) the subsequent antibody (Ab) immobilization, either directly by hydrogen bonding (HB) interactions or by covalent bonds (CB) using additional reagents, and (iii) measuring the biosensor response by electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). The electrode surfaces at each stage of the modification process were characterised by X-ray photo-electron spectroscopy (XPS) and atomic force microscopy (AFM). The combination of Ab immobilization by HB with the DPV analysis displayed improved repeatability, lower interference to serum matrix and similar limits of detection and quantification than the traditional biosensors that immobilize the Ab via CB and use EIS as readout technique. The Ab immobilization by HB is shown as a simple, efficient and low-cost alternative to CB ones, while DPV was faster and showed better performance than EIS. The CT-HB biosensor displayed the lowest limits of detection and quantification of 0.14 and 0.46 ng/mL, respectively, a 0.46–12.5 ng/mL linear analytical range, and 100% of recovery for 1/10 human serum media during HBV surface antigen detection by DPV. Even, it preserved the initial sensing capability after 7 days of its fabrication.Graphical abstract

Supplementation of Plant-Based Freezing Extender With Cysteamine Preserves Quality Parameters and Fertility Potential of Buck Sperm During Cryopreservation Process.

Sperm cryopreservation in small ruminant is an efficient strategy to distribute spermatozoa for reproductive programmes, but this process reduces the fertility potential of frozen-thawed spermatozoa. The aim of the current research was to evaluate the impact of different concentrations of cysteamine (CYS) in soybean lecithin (SL)-based medium on postthawed buck semen quality and fertility potential. Semen samples were collected from five bucks, twice a week, then diluted in the SL-based extender containing different concentrations of CYS as follows: extender containing 0 mM (control, C0), 1 mM (C1), 2 mM (C2), 4 mM (C4) and 8 mM (C8) CYS. Motility characteristics, membrane integrity, abnormal morphology, mitochondrial activity, acrosome integrity, viability, apoptotic-like changes, lipid peroxidation, DNA fragmentation, ROS concentration, pregnancy rate and kidding rate were evaluated after freeze-thaw process. In results, C1 resulted in greater (p ≤ 0.05) total motility, progressive motility, average path velocity, membrane integrity, mitochondrial activity, acrosome integrity, viability, pregnancy rate and kidding rate compared to the other groups. Furthermore, supplementation of freezing medium with 1 mM of CYS presented lower (p ≤ 0.05) apoptotic-like changes, lipid peroxidation, DNA fragmentation and ROS concentration compared to the other groups. On the other hand, C8 presented the least (p ≤ 0.05) total motility, progressive motility, average path velocity, membrane integrity, mitochondrial activity, acrosome integrity and viability as well as the highest (p ≤ 0.05) apoptotic-like changes, lipid peroxidation, DNA fragmentation and ROS concentration compared to the other groups. Therefore, supplementation of freezing medium with 1 mM CYS could be a helpful strategy to protect buck's spermatozoa quality and fertility potential during cryopreservation process.

On the origin of cysteamine-induced duodenal cytotoxicity and type II ferroptosis.

Cysteamine (CA) induces duodenal ulcers in rodents (Selye and Szabo, Nature 244:458-459, 1973). Cysteine (Cys), a precursor for the formation of CA (via catabolism of coenzyme A), does not cause lesions in the duodenum (Szabo et al., J Pharmacol Exp Ther 223:68-76, 1982). CA also has antimutagenic and anticancer pharmacology (Fujisawa et al., PLoS ONE 7, 2012; Lee, Adv Pharmacol Pharm Sci 2023:2419444, 2023). We propose a mechanism of CA-induced cell death dependent on oxygen and CA dioxygenase (ADO) that can explain the 50-year-old mystery as to why CA is, but Cys is not, ulcerogenic. Those cells expressing coenzyme A-catabolizing enzymes are subject to a unique type of oxygen- and enzyme-bound-Fe2+-dependent death, type II ferroptosis.

Silver nanoparticles modified with MoS2 and β-cyclodextrin as SERS substrate for rapid determination of cysteamine hydrochloride in meat products

An efficient Surface-enhanced Raman scattering (SERS) method for the detection of cysteamine hydrochloride (CSH) was developed by synthesizing a composite substrate comprising silver nanoparticles (AgNPs) functionalized with MoS2 and β-cyclodextrin (β-CD). The enhanced Raman signals of CSH by β-CD/MoS2/AgNPs substrate were the contribution of electromagnetic enhancement (EM) as well as chemical enhancement (CM), and the enhancement factor (EF) can reach up to 3.11 × 106 (peak at 633 cm−1). Various instrumental techniques were used to characterize the substrate, such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and ultraviolet visible (UV–vis). The binding of β-CD/MoS2/AgNPs and CSH was confirmed by UV–vis and Fourier transform infrared (FT-IR). The optimal experimental conditions were determined by single factor experiments as well as response surface model. The influences of different metal ions and analogous drugs on the detection of CSH were investigated. Under optimum conditions, a good linear correlation (R = 0.9997) was established for CSH in the range of 10.00–1000.00 nmol/L, and the limit of detection (LOD) was as low as 0.78 nmol/L (S/N = 3). The contents of CSH in meat samples were detected. The recovery was 96.6–103.1 %, and the relative standard deviation (RSD) of the measurement was 0.7–3.9 % (n = 7).

Designing a novel electrochemical sensor based on Ni and Mg co-doped ZnO nanoparticles for the detection and quantification of cysteamine from bodily fluids

The current work reports a novel approach for the development of an electrochemical sensor based on Ni and Mg-co-doped ZnO nanoparticles (ZNMO) to detect and quantify cysteamine (CA). The chemical co-precipitation strategy was used to synthesize zinc oxide co-doped with magnesium and nickel which can be used as a catalyst material. FTIR, XRD, XPS, BET and SEM-EDX examinations were used to confirm the produced material. The surface of the glassy carbon electrode (GCE) was modified with ZNMO nanoparticles, resulting in a remarkable improvement in the surface area of the electrodes which in turn improved the response for CA compared to previously reported studies. This enhancement can be attributed to the superior catalytic activity of the material in electro-oxidizing CA. The electrochemical studies were carried out using the analytical techniques like cyclic voltammetry and differential pulse voltammetry using 0.1 M phosphate buffer saline as a supporting medium. This fabricated sensor, ZNMO nanoparticles modified GCE (ZNMO/GCE) has shown superior sensing characteristics, including high selectivity, sensitivity, stability, and repeatability, for the identification and quantification of CA. The sensor successfully confirmed the diffusion-controlled electrode technique. It exhibited the widest linear range, spanning from 1 nM to 2500 μM, which is the most impressive result ever reported. The limit of detection (LOD) was determined to be 0.75 nM. Additionally, at the developed sensor, a real-sample analysis was conducted using biological fluids. Hence, the fabricated ZNMO/GCE showed excellent electrocatalytic performance for CA sensing, making it suitable for real-time monitoring.

Cysteamine HCl Administration Impedes Motor and Olfactory Functions, Accompanied by a Reduced Number of Dopaminergic Neurons, in Experimental Mice: A Preclinical Mimetic Relevant to Parkinson's Disease.

Cysteamine hydrochloride (Cys-HCl) has been established as a potent ulcerogenic agent of the gastrointestinal (GI) system. GI dysfunction and olfactory deficits are the most common clinical symptoms of many movement disorders, including Parkinson's disease (PD). Cys-HCl has been shown to interfere with dopamine, a neurotransmitter crucial for motor, olfactory, and cognitive functions. However, the reports on the effect of Cys-HCl treatment on the behavioral aspects and functions of the dopamine system appear to be inconsistent. Therefore, we revisited the impact of Cys-HCl on the motor function in experimental mice using a battery of behavioral tests, such as the pole test (PT), beam-walking test (BWT), and rotarod test (RDT), while the olfactory ability and cognitive functions were examined through the buried-food test (BFT) and Y-maze test. Furthermore, we investigated the effect of Cys-HCl on the number of dopaminergic tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) and olfactory bulb (OB) of the experimental mice using immunohistochemistry. The results revealed that Cys-HCl administration in the mice induced significant impairments in their motor balance and coordination, as their movement-related performances were markedly reduced in terms of the behavioral tasks. Mice exposed to Cys-HCl showed pronounced reductions in their odor discrimination abilities as well as cognitive impairments. Strikingly, the number of TH-positive neurons was found to be reduced in the SN and OB of the Cys-HCl-treated group, which is a bonafide neuropathogenic hallmark of PD. This study highlights the potential neurotoxic effects of Cys-HCl in experimental brains and suggests further investigation into its role in the pathogenesis of Parkinsonism.

Antibacterial Hydrogel Adhesives Based on Bifunctional Telechelic Dendritic-Linear-Dendritic Block Copolymers.

Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.

Visualization and quantitative detection of foodborne Salmonella Typhimurium by functionalizing cysteamine (CS) stabilized gold nanoparticles (CS-AuNPs@phage)

Visualization and quantitative detection of foodborne Salmonella Typhimurium by functionalizing cysteamine (CS) stabilized gold nanoparticles (CS-AuNPs@phage)

A New and Rapid LC-MS/MS Method for the Determination of Cysteamine Plasma Levels in Cystinosis Patients.

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)'s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5-26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50-3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60-36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects.

Cysteamine Chemisorption at Mercury-Solution Interfaces in the Context of Redox and Microdissociation Equilibria.

The redox behavior and chemisorption of cysteamine (CA) at a charged mercury surface are described, with an emphasis on its acid-base properties supported by molecular dynamics and quantum mechanical calculations. It was found that CA forms chemisorbed layers on the surface of the mercury electrode. The formation of Hg-CA complexes is connected to mercury disproportionation, as reflected in peaks SII and SI at potentials higher than the electrode potential of zero charge (p.z.c.). Both the process of chemisorption of CA and its consequent redox transformation are proton-dependent. Also, depending on the protonation of CA, the formation of typical populations of chemisorbed conformers can be observed. In addition, cystamine (CA disulfide dimer) can be reduced on the mercury surface. Between the potentials of this reduction and peak SI, the p.z.c. of the electrode used can be found. Furthermore, CA can serve as an LMW catalyst for hydrogen evolution. The mechanistic insights presented here can be used for follow-up research on CA chemisorption and targeted modification of other metallic surfaces.

POTENTIAL OF NATURAL BIOACTIVE COMPOUNDS IN MANAGEMENT OF MELASMA

Melasma is a form of inherited hyper-melanosis that appears as asymmetrical, brown-colored, uneven, reticulated macules on UVR-exposed skin, particularly on the facial area. The etiopathogenesis of melasma has been linked to several causes, including UV exposure, endocrine factors, genetic predisposition, anti-epileptic medications, and various cosmetics. The initial course of treatment for hyperpigmentation involves applying topical formulations of widely used substances like kojic acid, glycolic acid, and hydroquinone. Pharmaceuticals such as melatonin, tranexamic acid, and cysteamine hydrochloride are administered orally in this process. Chemical peels and laser therapy are examples of second-line therapies that are applied under the direction of trained experts. Unfortunately, these treatments have certain drawbacks and complications, including erythema, dryness, and skin peeling, and they take time to work, necessitating the use of herbal formulations for the management of hyperpigmentation. Bioactive compounds isolated from plants, such as arbutin, aloesin, flavonoids, hesperidin, licorice, ellagic acids, genistein, and quercetin, inhibit melanogenesis without melanocytotoxicity by different mechanisms. This review provides information on natural bioactive compounds used for the management of melasma.

Physiological role of genes involved in taurine biosynthesis in fishes and in silico approach to determine transcription factors in their promoters’ zone

Taurine, an amino sulfonic acid that is sometimes referred to as an amino acid, is endogenously synthesized by the action of the key genes/enzymes: cysteine dioxygenase (cdo), cysteine sulfonate decarboxylase (csad), glutamate decarboxylase (gad), and 2-amino ethanethiol dioxygenase (ado). The taurine transporter (taut) also distributes this taurine formation across the plasma. These genes have been identified as important in different physiological processes such as reproduction, digestion, olfactory, visual, circulatory, and muscular systems. Thus, a literature review of these genes in fish has been described in the present work. Moreover, there is null information regarding the study of regulatory elements such as transcription factors (TFs) in taurine biosynthesis and transportation genes of fishes. In this interest and taking advantage of the availability of different sequence databases, bioinformatics can be applied as a first approach for an in silico identification of the putative TFs and transcription factor binding sites (TFBS) that might play an important role in regulating these genes. The results showed that some are commonly shared, whereas TFs and TFBs vary among fish species. Hence, binding sites for homeobox protein BarH-like 1 (BARX1), brain-specific homeobox protein homolog (BSX), helicase-like transcription factor (HLTF), homeobox protein Hox-A7 (HOXA7), homeobox protein Hox-B3 (HOXB3), homeobox protein Hox-B6 (HOXB6), homeobox protein Meis1 (MEIS1), homeobox protein Meis3 (MEIS3), nuclear factor of activated T cells 1 (NFATC1), and homeobox protein Nkx-6.2 (NKX6-2) were commonly found in the promoter regions of genes involved in taurine transportation and biosynthesis. Additionally, our results suggested that the frequency of HOXB3, a transcription factor involved in development, has repetitive TFBS sites in the promoter region of all species analyzed in the present study. Although bioinformatics gives us an approach to determine putative TFs and TFBS, further work is needed to verify how the found regulatory elements play a key role in taurine biosynthesis and transportation.

Effects of various levels of coated cysteamine hydrochloride in the diet on feed intake, digestibility, ruminal fermentation, and blood metabolites in growing Charolais crossbred cattle.

This study investigated the impact of different levels of coated cysteamine hydrochloride (CSH) supplementation on ruminal fermentation, nutrient digestibility, and blood metabolites in Charolais cross bulls. Twelve bulls were allotted to three feeding treatments in a replicated 3 × 3 Latin square design: 0% CSH (control), 0.5% CSH, and 1.0% CSH in concentrate. Animals were fed concentrate at 1.5% of body weight. Dry matter intake (DMI) and DMI as a percentage of body weight showed no significant differences among treatments (p > 0.10). Nutrient digestibility was consistent across treatments, except for a slight decrease in NDF digestibility with 1% CSH (p = 0.07). Ruminal pH, ammonia nitrogen, volatile fatty acid (VFA) proportions, and total VFA concentration were similar among treatments (p > 0.05). Total bacteria, fungal zoospores, and protozoa populations in the rumen did not vary significantly (p > 0.05). Blood glucose and triglyceride concentrations remained stable (p > 0.05), while blood urea nitrogen (BUN) levels were higher in CSH-supplemented groups (p < 0.05). In conclusion, incorporating CSH levels ranging from 0.5% to 1.0% into the diet did not adversely affect feed intake, ruminal fermentation, or microbial populations. Additionally, 1.0% CSH improved BUN concentration in growing Charolais cross bulls.

Altering the interfacial rheology of Pseudomonas aeruginosa and Staphylococcus aureus with N-acetyl cysteine and cysteamine.

Chronic lung infection due to bacterial biofilms is one of the leading causes of mortality in cystic fibrosis (CF) patients. Among many species colonizing the lung airways, Pseudomonas aeruginosa and Staphylococcus aureus are two virulent pathogens involved in mechanically robust biofilms that are difficult to eradicate using airway clearance techniques like lung lavage. To remove such biological materials, glycoside hydrolase-based compounds are commonly employed for targeting and breaking down the biofilm matrix, and subsequently increasing cell susceptibility to antibiotics. In this study, we evaluate the effects of N-acetyl cysteine (NAC) and Cysteamine (CYST) in disrupting interfacial bacterial films, targeting different components of the extracellular polymeric substances (EPS). We characterize the mechanics and structural integrity of the interfacial bacterial films using pendant drop elastometry and scanning electron microscopy. Our results show that the film architectures are compromised by treatment with disrupting agents for 6 h, which reduces film elasticity significantly. These effects are profound in the wild type and mucoid P. aeruginosa, compared to S. aureus. We further assess the effects of competition and cooperation between S. aureus and P. aeruginosa on the mechanics of composite interfacial films. Films of S. aureus and wild-type P. aeruginosa cocultures lose mechanical strength while those of S. aureus and mucoid P. aeruginosa exhibit improved storage modulus. Treatment with NAC and CYST reduces the elastic property of both composite films, owing to the drugs' ability to disintegrate their EPS matrix. Overall, our results provide new insights into methods for assessing the efficacy of mucolytic agents against interfacial biofilms relevant to cystic fibrosis infection.

Colorimetric detection of oral bacteria using functionalized gold nanoparticles as a plasmonic biosensor array.

Early detection of specific oral bacterial species would enable timely treatment and prevention of certain oral diseases. In this work, we investigated the sensitivity and specificity of functionalized gold nanoparticles for plasmonic sensing of oral bacteria. This approach is based on the aggregation of positively charged gold nanoparticles on the negatively charged bacteria surface and the corresponding localized surface plasmon resonance (LSPR) shift. Gold nanoparticles were synthesized in different sizes, shapes and functionalization. A biosensor array was developed consisting of spherical- and anisotropic-shaped (1-hexadecyl) trimethylammonium bromide (CTAB) and spherical mercaptoethylamine (MEA) gold nanoparticles. It was used to detect four oral bacterial species (Aggregatibacter actinomycetemcomitans, Actinomyces naeslundii, Porphyromonas gingivalis and Streptococcus oralis). The plasmonic response was measured and analysed using RGB and UV-vis absorbance values. Both methods successfully detected the individual bacterial species based on their unique responses to the biosensor array. We present an in-depth study relating the bacteria zeta potential and AuNP aggregation to plasmonic response. The sensitivity depends on multiple parameters, such as bacterial species and concentration as well as gold nanoparticle shape, concentration and functionalization.

Dramatic Electrochemical Tuning of the Plasmonic Spectrum of a Metal Nanoparticle on a Mirror

Enhancement of electric fields in the nanometric gap between plasmonic nanostructures is widely exploited for sensing, enhanced spectroscopies and photochemistry. Plasmonic properties of nanostructures with ultrathin gaps, such as nanoparticles (NPs) positioned on a flat metal surface (a mirror), have attracted much attention in recent years [1]. We studied the effect of electrochemical control on the plasmonic properties of single Au and Ag NPs on a mirror. We found that the coupled plasmonic resonance could be reversibly tuned over a range of tenths of nanometers, more than an order of magnitude higher than expected based just on capacitive charging of the NPs.Our experimental system consisted of single Au or Ag NPs (50 nm – 100 nm) adsorbed on a self-assembled monolayer (SAM) of either polyelectrolytes, cysteamine (CEA) or ethanedithiol (EDT) deposited on an atomically flat 100nm thick Au electrode prepared by template stripping. The NPs were either bare (prepared by H2 reduction) or citrate-stabilized and the system was immersed in a basic solution.Coupling to the mirror electrode resulted in the appearance of several bands in the plasmonic spectrum of individual NPs, as measured by dark-field microspectroscopy (Fig. 1a), and the lowest-energy band could be attributed to the coupled plasmon. Variation of the electrode potential generated a giant, though reversi shift of the spectrum. A plot of the peak position of the coupled plasmon band displayed an S-shaped, phase-transition like behavior (Fig. 1b).This remarkable result could not be observed with individual NPs deposited on non-metallic surfaces, and can therefore be attributed to a dramatic modulation of the coupling between the particles and the mirror with electrode potential.Figure 1. Scattering spectra (a) and variation of the spectral position of the coupled plasmon peak (b) of bare AuNP (ca. 60 nm) on CEA/Au electrode. Inset in (a): Scheme of NP on the mirror.

Development of thiolated xanthan gum-stearylamine conjugate based mucoadhesive system for the delivery of biochanin-A to melanoma cells

Recently, instead of creating new active compounds, scientists have been working to increase the bioavailability and residence time of existing drugs by modifying the characteristics of the delivery systems. In the present study, a novel mucoadhesive bioconjugate (SN-XG-SH) was synthesized by functionalizing a polysaccharide xanthan gum (XG) with cysteamine hydrochloride (CYS) and a lipid stearylamine (SN). FTIR, CHNS and 1H NMR studies confirmed the successful synthesis of SN-XG-SH. Mucoadhesion of the thiolated XG was enhanced and evaluated by different methods. Disulfide bond formation between thiolated XG and skin mucus enhances mucoadhesive behavior. The mucoadhesive bioconjugate was used to prepare nanoparticles for the delivery of hydrophobic biochanin-A (Bio-A) for the treatment of melanoma. The thiolated xanthan gum nanoparticles also demonstrated high drug entrapment efficiency, sustained drug release, and high storage stability. The drug loaded nanoparticles (Bio-A@TXNPs) significantly improved the cytotoxicity of Bio-A against human epidermoid cancer cells (A431 cells) by inducing apoptosis and changing mitochondrial membrane potential. In conclusion, thiolation of XG improves its mucoadhesive properties and prolongs the release of Bio-A. Thus, thiolated XG conjugate has a high potential for use as a bioadhesive agent in controlled and localised delivery of drugs in different skin diseases including melanoma.