High Concentration Of Glutathione Research Articles

Evaluation of Photoelectrochemical Glutathione Sensors Using of Electrochemical Impedance Spectroscopy

Human blood contains a high concentration of glutathione (GSH), which is an antioxidant component. The higher the concentration of the in-vivo GSH, the higher a risk of cancer. Therefore, it is important to detect the GSH concentration of the high density region. Photoelectrochemical sensors using photocatalyst can be kept low applied potential from becoming a source of energy from light and electricity. Therefore, high sensitivity sensing can be expected. According to the previous report, it was confirmed that a hybrid Au-TiO2 photocatalyst material can detect GSH. In this study, deeper studies were carried out in order to design a smarter and more sensitive GSH sensor. This is the method for manufacturing the electrode of the present study. Au-TiO2 thin film was prepared by two steps method. First, a mixture of titanium (IV) bis (ethyl acetoacetato) diisopropoxide and 1-butanol was spin-coated on FTO glass. Second, the coated FTO glass was calcined at 450 °C for 1 h. After cooling to room temperature, a solution of gold chloride dissolved in PVP, ethanol, and acetic acid was deposited on the TiO2-modified FTO glass using electrospinning (ES) method, and heated at 500 °C for 2 h. The physical properties of prepared film were evaluated by X-ray diffraction (XRD) and diffuse reflectance spectrum analysis. XRD was let found to be the titanium oxide of anatase type. In addition, the diffuse reflection showed an increase in the peak of gold due to the increased amount of gold (about 570 - 580 nm). The morphology of TiO2 is found to be fiber structure in our study. To reproducibly deposite titanium oxide film of the fiber is required to have humidity control, and it was possible to produce fiber membranes by increasing the humidity. This is because the hydrolysis tends to occur by high humidity. This study was performed on the impedance measurement using an electrolyte prepared by adding 0.5 mM of GSH in phosphate buffered saline (PBS). In this research, reference electrode is Ag/AgCl, counter electrode is platinum and the light source is a solar simulator (1 SUN). By changing the ES method, different samples of Au-TiO2 on FTO was prepared and electrochemical properties were measured. Equivalent circuit was designed in this experimental system. Charge transfer resistance and space charge layer capacitance between electrolyte interface with Au-TiO2 electrode were studied and fitted to the experimental results. The measurement results, loading of Au nanoparticles was decreased charge transfer resistance and increased space charge layer capacity (Fig.1). This indicates that carrier density in TiO2 would increase, which was further confirmed by Mott-Schottky plot. Therefore, recombination of exited electrons of TiO2 can be suppressed by modifying with Au nanoparticles. Furethermore, we measured chronoamperometry in order to know the concentration range that can be put to practical use as a sensor. GSH was then detected by the electrode (Au 0.1 g) and detection level is found to be in the range of 1 - 5 mM (Fig.2). From the above result, the fiber morphology as well as the loading of Au nanoparticles enable high-sensitivity sensing by using an electrode of Au 0.1 g, leading to the determination at a high concentration range. Reference 1) A. Devadoss et al., J. Mater. Chem B, 2016, 4, 220-228. Figure 1

Enhanced tumor delivery and antitumor response of doxorubicin-loaded albumin nanoparticles formulated based on a Schiff base.

A novel method was developed here to prepare albumin-based nanoparticles (NPs) for improving the therapeutic and safety profiles of chemotherapeutic agents. This approach involved crosslinking bovine serum albumin (BSA) using a Schiff base-containing vanillin, into NPs and loading doxorubicin (DOX) into the NPs by incubation. The resultant NPs (DOX-BSA-V-NPs) displayed a particle size of 100.5±1.3 nm with a zeta potential of −23.05±1.45 mV and also showed high drug-loading efficiency and excellent stability with respect to storage and temperature. The encapsulation of DOX into the BSA-V-NPs was confirmed by dynamic scanning calorimetry and Raman spectroscopy. DOX-BSA-V-NPs exhibited a significantly faster DOX release at pH 6.5 than pH 7.4, as well as in a solution with a higher glutathione concentration. In vitro studies showed that the cellular uptake of DOX-BSA-V-NPs was time-dependent, concentration-dependent, and faster than free DOX, while the cytotoxicity of DOX-BSA-V-NPs (IC50 value of 3.693 μg/mL) was superior to free DOX (IC50 value of 4.007 μg/mL). More importantly, DOX-BSA-V-NPs showed a longer mean survival time of 24.83 days, a higher tumor inhibition rate of 56.66%, and a decreased distribution in the heart than other DOX formulations in animal studies using a tumor xenograft model. Thus, the vanillin-based albumin NPs were shown here to be a promising carrier for tumor-targeted delivery of chemotherapeutic agents and, thus, should be further studied.

Impact of Sulfur Starvation in Autotrophic and Heterotrophic Cultures of the Extremophilic Microalga Galdieria phlegrea (Cyanidiophyceae).

In plants and algae, sulfate assimilation and cysteine synthesis are regulated by sulfur (S) accessibility from the environment. This study reports the effects of S deprivation in autotrophic and heterotrophic cultures of Galdieria phlegrea (Cyanidiophyceae), a unicellular red alga isolated in the Solfatara crater located in Campi Flegrei (Naples, Italy), where H2S is the prevalent form of gaseous S in the fumarolic fluids and S is widespread in the soils near the fumaroles. This is the first report on the effects of S deprivation on a sulfurous microalga that is also able to grow heterotrophically in the dark. The removal of S from the culture medium of illuminated cells caused a decrease in the soluble protein content and a significant decrease in the intracellular levels of glutathione. Cells from heterotrophic cultures of G. phlegrea exhibited high levels of internal proteins and high glutathione content, which did not diminish during S starvation, but rather glutathione significantly increased. The activity of O-acetylserine(thiol)lyase (OASTL), the enzyme synthesizing cysteine, was enhanced under S deprivation in a time-dependent manner in autotrophic but not in heterotrophic cells. Analysis of the transcript abundance of the OASTL gene supports the OASTL activity increase in autotrophic cultures under S deprivation.

Gated magnetic mesoporous silica nanoparticles for intracellular enzyme-triggered drug delivery

The targeting drug release is significant to the anticancer treatment. In this context, the redox-responsive drug delivery has attracted most attention owing to the intracellular reductive environment, such as the high concentration of glutathione reductase in many cancer cells. Herein, a glutathione sensitive drug delivery nanoplatform was constructed by using core-shell mesoporous silica nanocomposite (Fe3O4@mSiO2) as carrier. By a simple silane coupling reaction, the glutathione cleavable diselenide linker has been prepared and grafted on to Fe3O4@mSiO2 to insure the encapsulation of anticancer drug doxorubicin. The detail release kinetics studies reveal the glutathione triggered drug release, which could be further adjusted by varying the amount of diselenide linker. To improve the tumor-targeting, folic acid was grafted. The cellular uptake and drug release investigation was carried out using HeLa (cervical cancer cell line) as the model cancer cell and L02 and HUVEC (human hepatic cell line and human umbilical vein endothelial cells, non-cancerous cell lines) as control, indicating the enhanced cytotoxicity toward HeLa cells that benefits from the fast endocytosis and enhanced cellular drug release owing to their overexpressing folic acid receptors and high concentration of glutathione. Associating with the magnetic targeting, these novel nanomaterials are expected to be promising in the potential application of tumor-targeting therapy.

MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.

Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH.

Redox-responsive minimized fragmentation of three-armed oligo(ethylene glycol) gels for protein release

Redox-responsive drug delivery system (DDS) carriers cross-linked by disulfide bonds have attracted attention, because disulfide bonds can be cleaved in the presence of high glutathione (GSH) concentrations found in cancer cells. In this study, to obtain redox-responsive degradable hydrogels, three-armed oligo(ethylene glycol) (trisOEG) gels were prepared through terminal cross-linking reaction that linked together low-molecular-weight trisOEG molecules via a disulfide bond. The stability of the trisOEG gels was investigated in the presence of a reductant, dithiothreitol (DTT) or reduced GSH, in phosphate buffered saline solution. TrisOEG gels were fragmented by a redox-stimulus, returning the decomposed hydrophilic oligomers to a low-molecular-weight state, similar to the raw material that would be expected to be excreted in vivo by the renal system. In addition, protein-immobilized trisOEG micro-gels were prepared. While no release of entrapped protein from trisOEG micro-gel was observed in the absence of GSH, release of entrapped protein was observed in the presence of GSH at a concentration found in cytoplasm.

A Glutathione (GSH)-Responsive Near-Infrared (NIR) Theranostic Prodrug for Cancer Therapy and Imaging.

To reduce the side effects of chemotherapy, nontoxic prodrugs activated by the tumor microenvironment are urgently required for use in cancer treatment. In this work, we developed prodrug 4 for tumor-targeting treatment and imaging of the anticancer drug release in vivo. Taking advantage of the high glutathione (GSH) concentration in cancer cells, the disulfide bond in prodrug 4 was cleaved, resulting in the release of an active anticancer drug and a near-infrared (NIR) fluorescence dye turn-on. Furthermore, contrast to the free anticancer drug, the prodrug exhibited higher cytotoxicity to hepatoma cells than that to normal HL-7702 cells. Thus, prodrug 4 is a promising platform for specific tumor-activatable drug delivery system, because of its favorable features of in situ and in vivo monitoring of the drug release and therapeutic efficacy.

Composition of free and peptide-bound amino acids in beef chuck, loin, and round cuts1,2

Meat is a food for humans. However, beef consumption in the United States has steadily declined by >14% over the past decade due to a variety of factors, including insufficient knowledge of animal protein. This study quantified all proteinogenic AA as well as nutritionally and physiologically significant nonproteinogenic AA and small peptides in beef cuts from 3 subprimals (chuck, round, and loin). Beef carcasses ( = 10) were selected at 3 commercial packing plants in the United States. Retail-cut samples were analyzed for the nitrogenous substances after acid, alkaline, or enzymatic hydrolysis and after deproteinization. In these chuck, round, and loin cuts, total amounts of glutamate (free plus peptide bound) were the highest (69-75 mg/g dry weight) followed by lysine, leucine, arginine, and glutamine in descending order. This is the first study to determine aspartate, asparagine, glutamate, and glutamine in meat proteins of any animal species. In all the beef samples evaluated, glutamine was the most abundant free AA (4.0-5.7 mg/g dry weight) followed by taurine, alanine, glutamate, and β-alanine. Additionally, samples from all beef cuts had high concentrations of anserine, carnosine, and glutathione, which were 2.8 to 3.7, 15.2 to 24.2, and 0.68 to 0.79 mg/g dry weight, respectively. Beef top loin steaks appear to provide higher protein nutrition values than top round steaks and under blade roasts, but all are excellent sources of proteinogenic AA as well as antioxidant AA and peptides to improve human growth, development, and health. Our findings may help guide future decisions regarding human and animal nutrition.

Doxorubicin‐Loaded Metal–Organic Gels for pH and Glutathione Dual‐Responsive Release

AbstractAn emerging class of porous materials known as metal–organic gels (MOGs) has been gaining popularity due to their stability under reduced pressure and sensitivity to varying chemical environment. In this work, MOGs were used for the storage and controlled release of an anticancer drug, doxorubicin (Dox). In acidic pH or high concentration of glutathione, significant release of Dox from Dox‐loaded MOGs was observed. In addition, structural integrity of MOGs was disrupted in an acidic or glutathione‐containing environment, which was demonstrated by several characterization techniques. In vitro experiments on HeLa cancer cells showed the low toxicity of MOGs and further confirmed triggered drug release of Dox‐loaded MOGs. Based on the promising results obtained, Dox‐loaded MOGs present a great potential for future drug delivery applications.

Redox-Sensitive Citronellol-Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine.

Citronellol-cabazitaxel (CIT-ss-CTX) conjugate self-assembled nanoparticles (CSNPs) were designed and prepared by conjugating cabazitaxel with citronellol via the disulfide bond that is redox-sensitive to the high concentration of glutathione within tumor cells. Notably, the CSNPs maintained in the cell cytotoxicity. Moreover, the AUC0-t of CSNPs was 6.5-fold higher than that of cabazitaxel solutions and the t1/2 was prolonged 2.3 times. Furthermore, we found that CSNPs could be employed as an efficient carrier for other hydrophobic drugs or imaging agents. Thus, the in vivo targeting study was implemented via using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-loaded CSNPs as imaging agent, which showed CSNPs could effectively accumulate at the tumor site. Curcumin, a hydrophobic anticancer drug, was successfully loaded in CSNPs which exhibits good stability and synergistic antitumor effects. The citronellol-cabazitaxel conjugate therefore has a promising perspective as a multifunctional nanomedicine for combination therapy and theranostics attributed to its long-circulation property, redox-sensitive mechanism, and high drug coloading capability.

A Smart Photosensitizer-Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells.

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer-MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.

A Smart Photosensitizer–Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells

AbstractPhotodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species to kill cancer cells. However, a high concentration of glutathione (GSH) is present in cancer cells and can consume reactive oxygen species. To address this problem, we report the development of a photosensitizer–MnO2 nanosystem for highly efficient PDT. In our design, MnO2 nanosheets adsorb photosensitizer chlorin e6 (Ce6), protect it from self‐destruction upon light irradiation, and efficiently deliver it into cells. The nanosystem also inhibits extracellular singlet oxygen generation by Ce6, leading to fewer side effects. Once endocytosed, the MnO2 nanosheets are reduced by intracellular GSH. As a result, the nanosystem is disintegrated, simultaneously releasing Ce6 and decreasing the level of GSH for highly efficient PDT. Moreover, fluorescence recovery, accompanied by the dissolution of MnO2 nanosheets, can provide a fluorescence signal for monitoring the efficacy of delivery.

Characterisation of antioxidants in photosynthetic and non-photosynthetic leaf tissues of variegated Pelargonium zonale plants.

Hydrogen peroxide is an important signalling molecule, involved in regulation of numerous metabolic processes in plants. The most important sources of H2 O2 in photosynthetically active cells are chloroplasts and peroxisomes. Here we employed variegated Pelargonium zonale to characterise and compare enzymatic and non-enzymatic components of the antioxidative system in autotrophic and heterotrophic leaf tissues at (sub)cellular level under optimal growth conditions. The results revealed that both leaf tissues had specific strategies to regulate H2 O2 levels. In photosynthetic cells, the redox regulatory system was based on ascorbate, and on the activities of thylakoid-bound ascorbate peroxidase (tAPX) and catalase. In this leaf tissue, ascorbate was predominantly localised in the nucleus, peroxisomes, plastids and mitochondria. On the other hand, non-photosynthetic cells contained higher glutathione content, mostly located in mitochondria. The enzymatic antioxidative system in non-photosynthetic cells relied on the ascorbate-glutathione cycle and both Mn and Cu/Zn superoxide dismutase. Interestingly, higher content of ascorbate and glutathione, and higher activities of APX in the cytosol of non-photosynthetic leaf cells compared to the photosynthetic ones, suggest the importance of this compartment in H2 O2 regulation. Together, these results imply different regulation of processes linked with H2 O2 signalling at subcellular level. Thus, we propose green-white variegated leaves as an excellent system for examination of redox signal transduction and redox communication between two cell types, autotrophic and heterotrophic, within the same organ.

A redox-responsive mesoporous silica nanoparticle with a therapeutic peptide shell for tumor targeting synergistic therapy.

In this study, we report a novel redox-responsive mesoporous silica nanoparticle (MSN)-based nanocarrier, capping with a therapeutic peptide ((RGDWWW)2KC) containing a RGD target motif, for tumor targeting synergistic therapy, which is designated as TTSTMSN. The MSN was decorated with a tumor-targeting therapeutic peptide as a potential gatekeeper. The two branched peptides containing rich tryptophans allowed the pores to be blocked via π-π stacking and hydrophobic interactions. Once the drug loaded nanoparticles were taken up by the cancer cells through integrin-mediated endocytosis, the therapeutic peptide capping shells on the surface of MSNs were released, inducing the loaded drug to diffuse into the cytoplasm after breaking of the disulfide bonds, triggered by the high concentration of glutathione (GSH) in cancer cells. At the same time, the falling therapeutic rich tryptophans in the branched chains interacted with DNA due to the indole rings, leading to disturbance of the DNA structure through the strong π interactions and causing cell apoptosis. There is no such report on capping of drug loaded porous silica with a therapeutic peptide shell, co-delivering an anticancer drug and therapeutic agent for tumor targeting synergistic therapy, which will have great potential in developing multifunctional nanocarriers based on therapeutic peptides for synergistic treatment.

Dietary flavonoids advance timing of moult but do not affect redox status of juvenile blackbirds (Turdus merula).

Flavonoids are the most abundant plant polyphenols, widely occurring in fruits and berries, and show a strong antioxidant activity in vitro Studies of avian species feeding on berries suggest that dietary flavonoids have health-promoting effects and may enhance the expression of melanin-based plumage traits. These effects are probably mediated by the antioxidant activity of flavonoids. However, the effect of dietary flavonoids on oxidative status has never been investigated in any bird species. We analysed the effects of dietary flavonoids on blood non-enzymatic antioxidants and protein oxidative damage of juvenile European blackbirds (Turdus merula). In addition, we analysed the effects of flavonoid-enriched diet on body condition and on the timing of moult from juvenile to adult plumage. Dietary flavonoids did not significantly affect redox status but significantly advanced the onset of moult, hastening plumage development. Moulting birds showed higher protein oxidative damage compared with those that had not yet started moulting. The probability of initiating moult after 40 days of dietary treatment was higher for birds with low circulating levels of oxidizing agents and high glutathione concentration. The metabolization of flavonoids could have altered their redox potential, resulting in no net effects on redox status. However, flavonoid consumption before and during moult may contribute to enhance plumage development. Moreover, our findings suggest that moulting feathers may result in redox imbalance. Given their effect on moult and growth of melanin-rich feathers, fruit flavonoids may have contributed to shape plant fruiting time in relation to fruit consumption preferences by birds.

Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.

Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.

"Stealthy" chitosan/mesoporous silica nanoparticle based complex system for tumor-triggered intracellular drug release.

Suitable protection strategies utilized in anticancer drug delivery systems enable carriers to reach their targeted positions and release drugs intracellularly more effectively. In this study, a novel "stealthy" chitosan (CHI)/mesoporous silica nanoparticle (MSN) based complex system, named DOX@MSN-SS-CHI-PEG, was developed for tumor-triggered intracellular drug release. CHI was applied to block the pores of MSNs to prevent premature drug release, whereas mPEG was grafted on the surface of the nanoparticles via a pH-sensitive benzoic imine linker to protect the carriers. As the pH of solid tumor tissues is slightly lower than that of normal tissues, mPEG could leave the nanoparticles to expose positively charged CHI at the surface, which enabled the nanoparticles to enter cancer cells more easily. The MSNs were covered by CHI via redox-sensitive disulfide bonds. As a result, the carriers could release the drug intercellularly to kill cancer cells owing to the high concentration of glutathione (GSH) in the cytosol. In vitro drug release studies at different GSH concentrations proved the redox-sensitivity of DOX@MSN-SS-CHI-PEG. mPEG leaving studies demonstrated that mPEG could leave the nanoparticles effectively at pH 6.0. The cytotoxicity and cell internalization behavior were also investigated in detail. In conclusion, the novel DOX@MSN-SS-CHI-PEG drug delivery system, which was "stealthy" in the physiological environment at pH 7.4 because of the protection of mPEG, was "activated" in weakly acidic tumor tissues to achieve tumor-triggered intracellular drug release; this system has great potential for cancer therapy.

Variations in leaf total protein, phenolic and thiol contents amongst old varieties of mulberry from the Gorizia region

Abstract Preserving the plant genetic resources of genus Morus is insuff­cient but undoubtedly vital for conservation of the world’s germplasm for our successors. This research was focused on old mulberry varieties from the Gorizia region in Slovenia which were assessed for their contents on crucial metabolites (proteins, phenolics and thiols) in leaves regarding their antioxidant and nutraceutical potentials. Total proteins were measured spectrophotometrically by following the procedure of Bradford, the total phenolic contents were determined using the Folin-Ciocalteu method and thiols were established with monobromobimane fluorescent dye. The presented metabolite screening showed that some of the evaluated genotypes had higher concentrations of glutathione and were superior in contents of proteins and phenolics when compared to the results of other authors and could be propagated as highly recommendable feed for silkworms, and other animals.

Imaging-Guided Drug Release from Glutathione-Responsive Supramolecular Porphysome Nanovesicles.

Drug delivery systems that can be employed to load anticancer drugs and release them triggered by a specific stimulus, such as glutathione, are of great importance in cancer therapy. In this study, supramolecular porphysome nanovesicles that were self-assembled by amphiphilic porphyrin derivatives were successfully constructed, mainly driven by the π-π stacking, hydrogen bonding, and hydrophobic interactions, and were used as carriers of anticancer drugs. The nanovesicles are monodispersed in shape and uniform in size. The drug loading and in vitro drug release investigations indicate that these nanovesicles are able to encapsulate doxorubicin (DOX) to achieve DOX-loaded nanovesicles, and the nanovesicles could particularly release the loaded drug triggered by a high concentration of glutathione (GSH). More importantly, the drug release in cancer cells could be monitored by fluorescent recovery of the porphyrin derivative. Cytotoxicity experiments show that the DOX-loaded nanovesicles possess comparable therapeutic effect to cancer cells as free DOX. This study presents a new strategy in the fabrication of versatile anticancer drug nanocarriers with stimuli-responsive properties. Thus, the porphysome nanovesicles demonstrated here might offer an opportunity to bridge the gap between intelligent drug delivery systems and imaging-guided drug release.

Efficient RNA delivery by integrin-targeted glutathione responsive polyethyleneimine capped gold nanorods

RNA interference (RNAi) mediated gene silencing holds significant promises in gene therapy. A major obstacle to efficient RNAi is the systemic delivery of the therapeutic RNAs into the cytoplasmon without being trapped in intracellular endo-/lyso-somes. Herein we report the development of a PEGylated, RGD peptide modified, and disulfide cross-linked short polyethylenimines (DSPEIs) functionalized gold nanorod (RDG) for targeted small hairpin (sh)RNA delivery. The RDG effectively condensed shRNAs into stable nanoparticles, allowing for highly specific targeting of model human brain cancer cells (U-87 MG-GFP) via the αvβ3 integrins-mediated endocytosis. The combined effects of endosomal escape (via the proton-sponge effect of the PEIs) and efficient cleavage of the disulfide-cross-linked DSPEIs by the high intracellular glutathione content triggered rapid cytoplasma shRNAs release resulting in excellent RNAi efficiency and low cytotoxicity. Furthermore, the high stability and prolonged blood circulation afforded by PEGylation allowed for highly effective, targeted tumor accumulation and internalization of the carriers, resulting in outstanding intra-tumor gene silencing efficiency in U-87 MG-GFP tumor bearing BALB/c mice. Combining the capabilities of both passive and active targeting, intracellular glutathione-triggered “off–on” release and endosomal escape, the RDG nanocarrier developed herein appears to be a highly promising non-viral vector for efficient RNAi.