[Determination of glutathione in cells by capillary electrophoresis-laser induced fluorescence].

Glutathione (GSH) is vital for oxidative stress resistance and heavy metals detoxification. It is significant to develop a sensitive and accurate quantitative GSH approach for the toxicity mechanism for studying heavy metals in cells. A high-sensitive capillary electrophoresis-laser induced fluorescence (CE-LIF) detection approach was proposed in this study to detect GSH content in cells. The approach employed HepG2 cells as an object and 2,3-naphthalenedicarboxaldehyde (NDA) with the active group of aromatic o-dialdehyde as a labeling reagent. The effects of buffer solution types, pH, additives on the GSH reaction rate with NDA, and the sensitivity of NDA-GSH were systematically investigated. The sensitivity of NDA-GSH and the reaction rate of GSH with NDA were compared in tris(hydroxymethyl)aminomethane (Tris) buffer solution at pH 7.4 or 9.2 and borate-Tris buffer solution at pH 9.2. The results revealed that the NDA-GSH sensitivity was the highest and the reaction rate of GSH and NDA was the fastest in borate buffer solution at pH 9.2. The effects of the four additives on the sensitivity of NDA-GSH were further compared. The best additive was revealed to be ß-cyclodextrin (ß-CD). GSH reacted with NDA to reach equilibrium within 5 min under the optimal experimental conditions, and the electrophoretic signal of NDA-GSH could be seen in 3 min. Quantitative analysis of GSH in HepG2 cells was performed using an external standard approach by determining a series of GSH standard solutions. The results revealed that the approach had a good linear relationship with the peak area vs. concentration (0.01-20.00 mmol/L) of GSH. The limit of detection (LOD) and limit of quantification (LOQ) of GSH were determined using signal-to-noise ratios of 3 (S/N=3) and 10 (S/N=10), which were 0.006 µmol/L and 0.020 µmol/L, respectively. The approach's spiked recoveries were 95.7%-112.6%, with relative standard deviations of the approach being 3.8%-5.0% (n=3). This approach offers high sensitivity, good stability, accuracy, and reliability. To study the relationship between the toxicity of arsenic and chromium on HepG2 cells and the content of GSH in HepG2 cells, the effects of arsenic and chromium with different valences on cell viability were analyzed. The results illustrated that the cytotoxicity of potassium dichromate (Cr(Ⅵ)) was the strongest. The variations of GSH content in HepG2 cells stimulated with arsenite (As(Ⅲ)), arsenate (As(Ⅴ)), chromium chloride (Cr(Ⅲ)), and Cr(Ⅵ) were analyzed by the proposed approach and analysis of intracellular GSH imaging. The results revealed that the stimulation group i. e. analyzed doses (low-dose 2 mg/L, high-dose 5 mg/L) of As(Ⅲ), As(Ⅴ), and Cr(Ⅲ) had no obvious effect on GSH content in HepG2 cells compared with the control group, whereas high-dose Cr(Ⅵ) can significantly reduce GSH content in HepG2 cells. Considering the analysis of cytotoxicity of As(Ⅲ), As(Ⅴ), Cr(Ⅲ), and Cr(Ⅵ), it shows that the content of GSH in HepG2 cells is related to cytotoxicity, and the content of GSH will decrease with the increase in cytotoxicity.

Glutathione-modified graphene quantum dots as fluorescent probes for detecting organophosphorus pesticide residues in Radix Angelica Sinensis.

A novel fluorescent sensor was developed in this study based on glutathione-functionalized graphene quantum dots (GQDs@GSH) to detect organophosphorus pesticide residues in Radix Angelica Sinensis. GQDs@GSH was synthesized by a one-step pyrolysis method with a fluorescence quantum yield as high as 33.9% and its structure was characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. GQDs@GSH exhibited excellent fluorescence property showing strong blue fluorescence under UV irradiation. The fluorescence of GQDs@GSH could be quenched by Fe3+ by electron transfer and the quenched fluorescence could be recovered due to the strong chelating and reducing ability of phytic acid (PA). Under the catalyzation of acetylcholinesterase (AChE) and choline oxidase (ChOx), acetylcholine (ACh) could be decomposed to H2O2, which could further oxidize Fe2+ to Fe3+ thus quenching the fluorescence of GQDs@GSH once again. Coumaphos, a kind of organophosphorus pesticide, could inhibit AChE activity, thus making the quenched fluorescence turn on again. Several parameters influencing the fluorescence response such as Fe3+, PA, ACh and coumaphos concentration, pH value and reaction time were optimized. Based on such a fluorescence "off-on-off-on" ngkmechanism, GQDs@GSH was successfully applied to the detection of coumaphos in Radix Angelica Sinensis. A good linear relationship between the fluorescence intensity and coumaphos concentration was obtained in the range of 0.1-10.0 µmol·L-1. By a standard addition method, the recoveries were measured to be 101.44-117.90% with RSDs lower than 1.98%. The biosensor system is simple, sensitive and accurate. It has a good application prospect in the detection of organophosphorus pesticide residues in traditional Chinese medicine and agricultural products, and also expanded the application scope for glutathione as a highly selective biological molecule.

Iron porphyrin-based porous organic polymer with high peroxidase-like activity as colorimetric sensor for glutathione and ascorbic acid assay.

A new iron porphyrin-based organic polymer (Fe-POP) was synthesized through the William ether reaction. The as-prepared Fe-POP presented high chemical stability, wide pore distribution, high iron content, and strong affinity with 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2), which contributed to its excellent peroxidase-mimicking performance. In the presence of H2O2, Fe-POP could catalyze the transparent TMB into blue ox-TMB, which could be easily distinguished by the naked eyes. Moreover, glutathione (GSH) and ascorbic acid (AA) could convert blue ox-TMB into colorless TMB due to the inhibitory effect of GSH/AA to the catalytic oxidation of TMB. Based on this phenomenon, a rapid and sensitive colorimetric method for the assay of H2O2, GSH, and AA was developed using Fe-POP as sensor. The detection limits of H2O2, GSH, and AA  were 1.37, 0.44, and 0.33 µM, respectively. Finally, the colorimetric method based on Fe-POP was used to evaluate the GSH and AA content in real samples, which provided the guidance for GSH and AA supplements in our daily diet, suggesting the significant potential of Fe-POP in practical applications.

Self-Sacrificially Degradable Pseudo-Semiconducting Polymer Nanoparticles that Integrate NIR-II Fluorescence Bioimaging, Photodynamic Immunotherapy, and Photo-Activated Chemotherapy.

Semiconducting polymers (SP) hold great promise for cancer phototherapy due to their excellent optical properties; however, their clinical application is still hampered by their poor biodegradability. Herein, a self-sacrificially biodegradable pseudo-semiconducting polymer (PSP) for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and photoactivated chemotherapy (PACT) is reported. The PSP can further co-assemble with an amphiphilic polyester with pendant doxorubicin (DOX) in its side chains via reactive oxygen species (ROS)-responsive thioketal linkages (PEDOX ), which are denoted as NP@PEDOX /PSP. The NP@PEDOX /PSP can accumulate at tumor sites and generate ROS for photodynamic immunotherapy as well as near-infrared-II fluorescence (NIR-II) for bioimaging upon irradition at 808 nm. The ROS could break up thioketal linkages in PEDOX , resulting in rapid doxorubicin (DOX) release for PACT. Finally, both PEDOX and PSP are degraded sacrificially by intracellular glutathione (GSH), resulting in the dissociation of NP@PEDOX /PSP. This work highlights the application of self-sacrificially degradable PSP for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and PACT in cancer therapy.

Where are we with the use of N-acetylcysteine as a preventive and adjuvant treatment for COVID-19?

OBJECTIVE: As N-acetylcysteine (NAC) is promising as a re-purposed drug for the adjunctive or supportive treatment of serious COVID-19, this article aimed to describe current evidence. MATERIALS AND METHODS: A search was performed in PubMed/Medline for "NAC", "viral Infection", COVID-19", oxidative stress", "inflammation", retrieving preclinical and clinical studies. RESULTS: NAC is a pleiotropic molecule with a dual antioxidant mechanism; it may neutralize free radicals and acts as a donor of cysteine, restoring the physiological pool of GSH. Serious COVID-19 patients have increased levels of reactive oxygen species (ROS) and free radicals and often present with glutathione depletion, which prompts a cytokine storm. NAC, which acts as a precursor of GSH inside cells, has been currently used in many conditions to restore or protect against GSH depletion and has a wide safety margin. In addition, NAC has anti-inflammatory activity independently of its antioxidant activity. CONCLUSIONS: Clinical and experimental data suggest that NAC may act on the mechanisms leading to the prothrombotic state observed in severe COVID-19.

Nanosilver-Decorated Biodegradable Mesoporous Organosilica Nanoparticles for GSH-Responsive Gentamicin Release and Synergistic Treatment of Antibiotic-Resistant Bacteria.

PURPOSE: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria. METHODS: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated. RESULTS: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 µg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. CONCLUSION: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.

Glutathione-Conjugated Hydrogels: Flexible Vehicles for Personalized Treatment of Bacterial Infections.

PURPOSE: Skin and soft tissue infections are increasingly prevalent and often complicated by potentially fatal therapeutic hurdles, such as poor drug perfusion and antibiotic resistance. Delivery vehicles capable of versatile loading may improve local bioavailability and minimize systemic toxicities yet such vehicles are not clinically available. Therefore, we aimed to expand upon the use of glutathione-conjugated poly(ethylene glycol) GSH-PEG hydrogels beyond protein delivery and evaluate the ability to deliver traditional therapeutic molecules. METHODS: PEG and GSH-PEG hydrogels were prepared using ultraviolet light (UV)-polymerization. Hydrogel loading and release of selected drug candidates was examined using UV-visible spectrometry. Therapeutic molecules and GST-fusion protein loading was examined using UV-visible and fluorescent spectrometry. Efficacy of released meropenem was assessed against meropenem-sensitive and -resistant P. aeruginosa in an agar diffusion bioassay. RESULTS: For all tested agents, GSH-PEG hydrogels demonstrated time-dependent loading whereas PEG hydrogels did not. GSH-PEG hydrogels released meropenem over 24 h. Co-loading of biologic and traditional therapeutics into a single vehicle was successfully demonstrated. Meropenem-loaded GSH-PEG hydrogels inhibited the growth of meropenem-sensitive and resistant P. aeruginosa isolates. CONCLUSION: GSH ligands within GSH-PEG hydrogels allow loading and effective delivery of charged therapeutic agents, in addition to biologic therapeutics.

Investigating the antimicrobial, antioxidant and cytotoxic activities of the biological synthesized glutathione selenium nano-incorporation.

Aqueous glutathione selenium nano-incorporation (GSH-SeN-Inco) was prepared by gamma radiation in presence of microbial glutathione (GSH) and selenium dioxide. The novel prepared GSH-SeN-Inco are validated by UV-vis spectroscopy, TEM (17.5 nm), DLS, XRD, EDX and FTIR spectrum reveals the presence of GSH moiety that coating the selenium nanoparticles (SeNPs) forming GSH-SeN-Inco. The XRD analysis verified the presence of metallic SeNPs. The nucleation and radiolysis mechanism of GSH-SeN-Inco formation are also discussed. The size GSH-SeN-Inco (17.5 nm) is affected by certain factors such as concentration of GSH, selenium dioxide, and absorbed dose of gamma radiation. The present study explored the positive role of GSH-SeN-Inco as an antitumor activity against HepG-2 and MCF-7, with IC50 at a concentration of 1.00 and 0.9 mM, respectively. The GSH-SeN-Inco show significant scavenging activity at 33%. The GSH-SeN-Inco shows antimicrobial potential against Gram-negative and Gram-positive bacteria with significant MIC especially Escherichia coli ATCC 25922 at 5.20 µg/ml.

Biodegradable flower-like manganese for synergistic photothermal and photodynamic therapy applications.

A flower-like nanostructured MnO2 with near-infrared (NIR) light-triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed. Different from the reported MnO2 nanomaterials those were used in the nanomedicine field for only relieving tumor hypoxia and/or imaging, the flower-like MnO2 inherently acts as a competent agent for simultaneously enhanced photothermal and photodynamic therapy. A flower-like nanostructured MnO2 with near-infrared (NIR) light triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed.

Photocatalysis-mediated drug-free sustainable cancer therapy using nanocatalyst.

Drug therapy unavoidably brings toxic side effects and drug content-limited therapeutic efficacy although many nanocarriers have been developed to improve them to a certain extent. In this work, a concept of drug-free therapeutics is proposed and defined as a therapeutic methodology without the use of traditional toxic drugs, without the consumption of therapeutic agents during treatment but with the inexhaustible therapeutic capability to maximize the benefit of treatment, and a Z-scheme SnS1.68-WO2.41 nanocatalyst is developed to achieve near infrared (NIR)-photocatalytic generation of oxidative holes and hydrogen molecules for realizing combined hole/hydrogen therapy by the drug-free therapeutic strategy. Without the need of any drug and other therapeutic agent assistance, the nanocatalyst oxidizes/consumes intratumoral over-expressed glutathione (GSH) by holes and simultaneously generates hydrogen molecules in a lasting and controllable way under NIR irradiation. Mechanistically, generated hydrogen molecules and GSH consumption inhibit cancer cell energy and destroy intratumoral redox balance, respectively, to synergistically damage DNA and induce tumor cell apoptosis. High efficacy and biosafety of combined hole/hydrogen therapy of tumors are achieved by the nanocatalyst. The proposed catalysis-based drug-free therapeutic strategy breaks a pathway to realize high efficacy and low toxicity of cancer treatment.

Discussions of Fluorescence in Selenium Chemistry: Recently Reported Probes, Particles, and a Clearer Biological Knowledge.

In this review from literature appearing over about the past 5 years, we focus on selected selenide reports and related chemistry; we aimed for a digestible, relevant, review intended to be usefully interconnected within the realm of fluorescence and selenium chemistry. Tellurium is mentioned where relevant. Topics include selenium in physics and surfaces, nanoscience, sensing and fluorescence, quantum dots and nanoparticles, Au and oxide nanoparticles quantum dot based, coatings and catalyst poisons, thin film, and aspects of solar energy conversion. Chemosensing is covered, whether small molecule or nanoparticle based, relating to metal ion analytes, H2S, as well as analyte sulfane (biothiols-including glutathione). We cover recent reports of probing and fluorescence when they deal with redox biology aspects. Selenium in therapeutics, medicinal chemistry and skeleton cores is covered. Selenium serves as a constituent for some small molecule sensors and probes. Typically, the selenium is part of the reactive, or active site of the probe; in other cases, it is featured as the analyte, either as a reduced or oxidized form of selenium. Free radicals and ROS are also mentioned; aggregation strategies are treated in some places. Also, the relationship between reduced selenium and oxidized selenium is developed.

Influence of dough composition on the formation of processing contaminants in yeast-leavened wheat toasted bread.

The influence of dough composition on acrylamide, 3-monochloropropane-1,2-diol (3-MCPD) esters, and glycidyl esters (GE) formation during bread toasting was investigated. The doughs differed in added amounts of soy lecithin, salt, and reducing agents (l-cysteine and glutathione). The toasting of bread for 2.5 min considerably enhanced the formation of acrylamide and 3-MCPD esters. The addition of lecithin (1%, w/w) resulted in four times higher content of 3-MCPD esters in toasted bread slices. No distinct relationship between dough composition and GE formation in untoasted and toasted bread was found. The addition of reducing agents (0.05%, w/w) mitigated during toasting not only the formation of 3-MCPD esters (more than six times) but also the extent of Maillard reaction that resulted in three times lower amounts of acrylamide and predominant formation of alcohol-like compounds. Toasted bread without reducing agents contained typical Maillard reaction compounds such as aldehydes, alkyl pyrazines, and derivatives of furan.

Design and Fabrication of Dual Redox Responsive Nanoparticles with Diselenide Linkage Combined Photodynamically to Effectively Enhance Gene Expression.

BACKGROUND: PEI is currently the most used non-viral gene carrier and the transfection efficiency is closely related to the molecular weight; however, the prominent problem is that the cytotoxicity increased with the molecular weight. METHODS: A novel redox responsive biodegradable diselenide cross-linked polymer (dPSP) was designed to enhance gene expression. ICG-pEGFP-TRAIL/dPSP nanoparticles with high drug loading are prepared, which have redox sensitivity and plasmid protection. The transfection efficiency of dPSP nanoparticle was evaluated in vitro. RESULTS: The plasmid was compressed by 100% at the N/P ratio of 16, and the particle size was less than 100 nm. When explored onto high concentrations of GSH/H2O2, dPSP4 degraded into small molecular weight cationic substances with low cytotoxicity rapidly. Singlet oxygen (1O2) was produced when indocyanine green (ICG) was irradiated by near-infrared laser irradiation (NIR) to promote oxidative degradation of dPSP4 nanoparticles. Under the stimulation of NIR 808 and redox agent, the particle size and PDI of ICG-pDNA/dPSP nanoparticle increased significantly. CONCLUSION: Compared with gene therapy alone, co-transportation of dPSP4 nanoparticle with ICG and pEGFP-TRAIL had better antitumor effect. Diselenide-crosslinked polyspermine had a promising prospect on gene delivery and preparation of multifunctional anti-tumor carrier.

High peroxidase-mimicking activity of gold@platinum bimetallic nanoparticle-supported molybdenum disulfide nanohybrids for the selective colorimetric analysis of cysteine.

Herein, gold@platinum (Au@Pt) bimetallic nanoparticles with high catalytic ability were in situ decorated onto a molybdenum disulfide (MoS2) surface to obtain nanocomposites (MoS2-Au@Pt) with high peroxidase-mimicking activity, which were used to construct a colorimetric sensor for cysteine (Cys) detection. Interestingly, this sensor can efficiently distinguish Cys from homocysteine (Hcy), glutathione (GSH) and 19 other amino acids with high sensitivity. As expected, the colorimetric sensor can determine the Cys content in Cys supplement tablets due to its high stability and repeatability. Finally, the detection mechanism was studied.

Targeted copper supplementation oriented theranostic for fluorescence and 19F NMR detection of tumors.

Alteration of the levels of copper is a promising approach for cancer therapy. Herein, we develop a dual-mode copper vehicle, M985. The biotin-tailed M985 can exert tumor-directed copper supplementation and undergo self-immolative cleavage in living cancerous cells, resulting in the liberation of F542 along with the generation of excess reactive oxygen species. Thus, fluorescence and 19F NMR detection is realized to specifically discriminate cancer cells. F542 acts as a fluorescence reporter and a potent cytotoxic agent, facilitating the visualization of molecular release and distribution, as well as confirming the ER autophagy-induced apoptosis. Therefore, we present a promising dual-mode theranostic M985 for the efficient detection and therapy of cancer.

Protective Role of Glutathione against Peroxynitrite-Mediated DNA Damage During Acute Inflammation.

Inflammation is an immune response to protect against various types of infections. When unchecked, acute inflammation can be life-threatening, as seen with the current coronavirus pandemic. Strong oxidants, such as peroxynitrite produced by immune cells, are major mediators of the inflammation-associated pathogenesis. Cellular thiols play important roles in mitigating inflammation-associated macromolecular damage including DNA. Herein, we have demonstrated a role of glutathione (GSH) and other thiols in neutralizing the effect of peroxynitrite-mediated DNA damage through stable GSH-DNA adduct formation. Our observation supports the use of thiol supplements as a potential therapeutic strategy against severe COVID-19 cases and a Phase II (NCT04374461) open-label clinical trial launched in early May 2020 by the Memorial Sloan Kettering Cancer Center.

Bromelain from Ananas comosus stem attenuates oxidative toxicity and testicular dysfunction caused by aluminum in rats.

BACKGROUND: Aluminum (Al) has been reported to induce testicular injury via oxidative stress. Ananas comosus stem extract is an inexpensive byproduct waste rich in bromelain which is a group of sulfur-containing enzymes known for its biological activities and medicinal applications. So, the current investigation aims to evaluate the efficacy of bromelain in counteracting oxidative injury and testicular dysfunction stimulated by aluminum in rats. METHODS: Male adult Wistar rats were divided into four groups. The first group used as control, however, the second and third groups were received bromelain (250 mg/kg) and AlCl3 (34 mg/Kg, 1/25 LD50), and the fourth group supplemented with bromelain one hour before AlCl3 intoxication, respectively. Bromelain was administered daily while AlCl3 was given every other day by oral gavages for one month. RESULTS: Al intoxicated animals revealed an elevation in lipid peroxidation (TBARS and H2O2) level and lactate dehydrogenase (LDH) activity. However, reduced glutathione (GSH) and protein contents, antioxidant enzymes (SOD, CAT, GPx, GR, GST), phosphatases (ALP, AcP) and aminotransferases (AST, ALT) activities were significantly reduced. Additionally, considerable amendments in hormonal levels (testosterone, luteinizing and follicle-stimulating hormone) and sperm characteristics were spotted. Further, histological variations in the testes section were detected and this supports the biochemical observations. Otherwise, rats supplemented with bromelain alone diminished TBARS and H2O2 and augmented mostly other parameters. Furthermore, supplementation with bromelain before Al intoxication in rats exhibited worthy betterment in oxidative stress markers, hormones, and sperm quality compared to Al treated group. CONCLUSION: In conclusion, bromelain had a powerful protective role against Al-induced testicular dysfunction so, it represents a novel approach in metal toxicity processing.

NIR multiphoton ablation of cancer cells, fluorescence quenching and cellular uptake of dansyl-glutathione-coated gold nanoparticles.

Theranostics based on two-photon excitation of therapeutics in the NIR region is an emerging and powerful tool in cancer therapy since this radiation deeply penetrates healthy biological tissues and produces selective cell death. Aggregates of gold nanoparticles coated with glutathione corona functionalized with the dansyl chromophore (a-DG-AuNPs) were synthesized and found efficient nanodevice for applications in photothermal therapy (PTT). Actually the nanoparticle aggregation enhances the quenching of radiative excitation and the consequent conversion into heat. The a-DG-AuNPs are readily internalized in Hep G2 where the chromophore acts as both antenna and transducer of the NIR radiation under two-photons excitation, determining efficient cell ablation via photothermal effect.

Exhibiting the diagnostic face of selenium nanoparticles as a radio-platform for tumor imaging.

Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes. A characteristic profile for the synthesized SeNPs was performed including size analysis, zeta potential, antioxidant activity, radiochemical yield and in-vivo biodistribution in normal and solid tumor bearing mice. Size analysis showed amorphous SeNP cores of a mean diameter of 21 ± 5 nm with a hydrodynamic size of 43 ± 8 nm and -28 mV zeta potential. The particles also showed a superior antioxidant activity of radical scavenging activity 55.6% according to DPPH assay, in addition, satisfying radiochemical yield up to 97 ± 1.5 was achieved. In vivo studies were applied on male Swiss albino mice that demonstrated a good biodistribution pattern in normal mice with a moderate accumulation in liver at 30 min post injection. Excellent T/NT ratios were obtained in solid tumor bearing mice throughout the experimental time points. The as-synthetized selenium nanoparticles demonstrated surprising and satisfying features which make them promising enough for tumor theranosis.

H2S-Donating trisulfide linkers confer unexpected biological behaviour to poly(ethylene glycol)-cholesteryl conjugates.

Inspired by the properties of the naturally occurring H2S donor, diallyl trisulfide (DATS, extracted from garlic), the biological behaviour of trisulfide-bearing PEG-conjugates was explored. Specifically, three conjugates comprising an mPEG tail and a cholesteryl head were investigated: conjugates bridged by a trisulfide linker (T), a disulfide linker (D) or a carbamate linker (C), and a fourth comprising two mPEG tails bridged by a trisulfide linker (P). H2S testing using both a fluorescent chemical probe in HEK293 cells and an amperometric sensor to monitor release in suspended cells, demonstrated the ability of the trisulfide conjugates, T and P, to release H2S in the presence of cellular thiols. Cytotoxicity and cyto-protective capacity on HEK293 cells showed that T was the best tolerated of the conjugates studied, and remarkably more so than D or C. Moreover, it was noted that application of T conferred a protective effect to the cells, effectively abolishing the toxicity associated with co-administered C. The interaction of conjugates and combinations thereof with the cell membrane of HEK cells, as well as ROS generation were also investigated. It was found that C caused significant membrane perturbation, correlating with high losses in cell viability and pronounced generation of ROS, especially in the mitochondria. T, however, did not disturb the membrane and was able to mitigate the generation of ROS, especially in the mitochondria. The interplay of the cholesteryl group and H2S donation for conferring cytoprotective effects was clearly demonstrated as P did not display the same beneficial characteristics as T.