Pluronic F127 self-assembled MoS2 nanocomposites as an effective glutathione responsive anticancer drug delivery system

In this study, bio-responsive polymeric MoS₂ nanocomposites were prepared for use as a drug carrier for cancer therapy. Herein, we report the synthesis and demonstrate the self-assembly of pluronic F127 (PF127) on a cystamine–glutathione–MoS₂ (CYS–GSH–MoS₂) system, which can be used for GSH-triggered drug release under biological reducing conditions. The reduction-sensitive disulfide bond containing CYS was incorporated between the amphiphilic copolymer PF127 and GSH–MoS₂ to achieve feasible drug release. Percent drug loading capacity and encapsulation efficiency were 51.3% and 56%, respectively. In addition, when the MoS₂–GSH–CYS–PF127 nanocomposite was incubated in a GSH environment, the morphology of the nanocomposite tended to change, ultimately leading to drug release. The drug-loaded PF127–CYS–GSH–MoS₂ polymeric nanocomposites efficiently released 52% of their drug content after 72 h of incubation in a GSH reduction environment. The HeLa cells treated with DOX loaded MoS₂–GSH–CYS–PF127 showed 38% toxicity at drug concentration of 40 μg, which indicated that the successfully released of drug from carrier and caused the cell death. Further, fluorescence microscopy images of HeLa cells revealed the potential behavior of the MoS₂–GSH–CYS–PF12 nanocomposite during the 2- and 4 h incubation periods; the nanocomposite was only found in the cytoplasm of HeLa cells. Interestingly, after 6 h of incubation, the drug was slowly released from the nanocomposite and could enter the nucleus as confirmed by fluorescence imaging of HeLa cells. Altogether, our synthesized PF127-coated MoS₂ nanocomposite could be effectively adopted in the near future as a GSH-sensitive drug carrier.

In this study, bio-responsive polymeric MoS₂ nanocomposites were prepared for use as a drug carrier for cancer therapy.     

Alcohol functionality in the fatty acid backbone of sphingomyelin guides the inhibition of blood coagulation

Cell-surface sphingomyelin (SM) inhibits binary and ternary complex activity of blood coagulation by an unknown mechanism. Here we show the OH functionality of SM contributes in forming the close assembly through intermolecular H-bond and through Ca²⁺ chelation, which restricts the protein–lipid/protein–protein interactions and thus inhibits the coagulation procedure.

Cell-surface sphingomyelin (SM) inhibits binary and ternary complex activity of blood coagulation.     

Fluorescent probe based on N-doped carbon dots for the detection of intracellular pH and glutathione

Carbon dots (CDs) as fluorescent probes have been widely exploited to detect biomarkers, however, tedious surface modification of CDs is generally required to achieve a relatively good detection ability. Here, we synthesized N-doped carbon dots (N-CDs) from triethylenetetramine (TETA) and m-phenylenediamine (m-PD) using a one-step hydrothermal method. When the pH increases from 3 to 11, the fluorescence intensity of the N-CDs gradually decreases. Furthermore, it displays a linear response to the physiological pH range of 5–8. Au³⁺ is reduced by amino groups on the surface of N-CDs to generate gold nanoparticles (AuNPs), causing fluorescence quenching of the N-CDs. If glutathione (GSH) is then added, the fluorescence of the N-CDs is recovered. The fluorescence intensity of the N-CDs is linearly correlated with the GSH concentration in the range of 50–400 μM with a limit of detection (LOD) of 7.83 μM. The fluorescence probe was used to distinguish cancer cells from normal cells using pH and to evaluate intracellular GSH. This work expands the application of CDs in multicomponent detection and provides a facile fluorescent probe for the detection of intracellular pH and GSH.

N-doped carbon dots used as a fluorescence probe can distinguish cancer cells from normal cells by pH and evaluate intracellular GSH.     

Glutathione-depleting polymer delivering chlorin e6 for enhancing photodynamic therapy

The therapeutic effect of photodynamic therapy (PDT) is highly dependent on the intracellular production of reactive oxygen species (ROS). However, the ROS generated by photosensitizers can be consumed by the highly concentrated glutathione (GSH) in tumor cells, severely impairing the therapeutic effect of PDT. Herein, we synthesized a GSH-scavenging copolymer to deliver photosensitizer chlorin e6 (Ce6). The pyridyl disulfide groups, which have faster reactivity with the thiol groups of GSH than other disulfide groups, were grafted onto a hydrophobic block to encapsulate the Ce6. Under NIR irradiation, the Ce6 generated ROS to kill tumor cells, and the pyridyl disulfide groups depleted the GSH to prevent ROS consumption, which synergistically enhanced the therapeutic effect of PDT. In vitro and in vivo experiments confirmed the combinatory antitumor effect of Ce6-induced ROS generation and the pyridyl disulfide group-induced GSH depletion. Therefore, the pyridyl disulfide group-grafted amphiphilic copolymer provides a more efficient strategy for enhancing PDT and has promising potential for clinical application.

We report a novel GSH-depleting polymer based on a thiol–pyridine disulfide exchange reaction, with fast reactivity and high efficiency in GSH depletion that effectively promotes ROS accumulation and significantly enhances photodynamic therapy.     

Turn-on signal fluorescence sensor based on DNA derived bio-dots/polydopamine nanoparticles for the detection of glutathione

A convenient, fast, sensitive and highly selective fluorescence sensor for the detection of glutathione (GSH) based on DNA derived bio-dots (DNA bio-dots)/polydopamine (PDA) nanoparticles was constructed. The fluorescent switch of DNA bio-dots was induced to turn off because of fluorescence resonance energy transfer (FRET) reactions between DNA bio-dots and PDA. The presence of GSH blocked the spontaneous oxidative polymerization of dopamine (DA) to PDA, leading the fluorescent switch of DNA bio-dots to be “turned on”. The degree of fluorescence recovery of DNA bio-dots is linearly correlated with the concentration of GSH within the range of 1.00–100 μmol L⁻¹, and the limit of detection (LOD) is 0.31 μmol L⁻¹ (S/N = 3, n = 9). Furthermore, the fluorescence sensor was successfully used to quantify GSH in human urine and glutathione whitening power, indicating the fluorescence sensor has potential in the detection of human body fluids and pharmaceutical preparations.

The turn-on fluorescence signal mechanism for detection of GSH.     

Mechanochemical synthesis of antifungal bis(benzoxaboroles)

Several piperazine bis(benzoxaboroles) have been obtained both in solution as well as in the solid state. The environmentally friendly mechanochemical approach – hitherto not applied for the preparation of benzoxaboroles – was particularly beneficial in the case of two products afforded in low yields in solution. The in vitro studies showed high potential of the studied bis(fluorobenzoxaboroles) as antifungal agents, highlighting also the influence of the fluorine substituent position on their microbiological activity. The highest activity against A. niger, A. terreus, P. ochrochloron, C. tenuis and C. albicans was displayed by the analogue of the known benzoxaborole antifungal drug Kerydin® (Tavaborole).

Several piperazine bis(benzoxaboroles) have been obtained mechanochemically – two of them have been shown to display high antifungal activity.     

Self-assembly of bovine serum albumin (BSA)–dextran bio-nanoconjugate: structural,antioxidant and in vitro wound healing studies

Glycation of proteins is often considered as a method to improve their functional properties for promising applications in wound healing. Furthermore, a marked increase in percentage of radical scavenging activity of the conjugates makes it an effective antioxidant synthetic strategy. A simple conjugation process was employed to develop bovine serum albumin–dextran conjugates (BSA–dextran) using Maillard reaction. Higher electrophoretic mobility and surface charge in the prepared conjugates was observed in native PAGE electrophoresis and zeta potential. Moreover, the fluorescence, FTIR and Raman analysis of the BSA–dextran conjugates shows significant shift in the fluorescence and wavelength as a consequence of conjugate formation. In vitro wound healing assay showed increased cell proliferation and migration effect. These finding suggests that BSA–dextran conjugate could open up a new practical way for exploration in the area of wound healing.

Glycation of proteins is often considered as a method to improve their functional properties for promising applications in wound healing.     

Bicyclo[6.1.0]nonyne carboxylic acid for the production of stable molecular probes

Bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN alcohol) is the most prominent strained-alkyne scaffold in chemical biology. Described herein is the synthesis of an oxidized analogue – BCN acid – whose facile functionalization via amide bond formation yields more stable derivatives than the classically encountered carbamates.

We report a novel strained alkyne, coined BCN acid. This compound participates efficiently in diverse bioorthogonal reactions and allows the facile production of amide probes, which showed superior in vitro stability compared to carbamate analogues.     

Dual-colour (near-infrared/visible) emitting annexin V for fluorescence imaging of tumour cell apoptosis in vitro and in vivo

Indocyanine green (ICG) labelled recombinant annexin V proteins (ICG–EGFP–Annexin V and ICG–mPlum–Annexin V) were synthesized for dual-colour fluorescence imaging of tumour cell apoptosis in vitro and in vivo. The ICG-labelled fluorescent annexin V proteins showed dual (near-infrared and visible) fluorescence emissions with binding ability to phosphatidylserines on the plasma membranes of apoptotic cells. Although several types of fluorescence labelled annexin V (e.g. FITC–annexin V, Cy3- and Cy5-annexin V) have been reported, there are no dual-colour (near-infrared/visible) emitting apoptosis-detection probes which can be used in vitro and in vivo. In this paper, the utilities of the dual-colour fluorescent annexin V are demonstrated for in vitro and in vivo fluorescence imaging of the apoptosis of human breast tumour cells induced by an antibody–drug conjugate, Kadcyla. The results suggest that the present annexin V probes will be useful to visualize the action of anti-cancer drugs against tumours both at the cellular and whole-body level.

Indocyanine green labeled recombinant annexin V probes (ICG–EGFP–Annexin V and ICG–mPlum–Annexin V) were synthesized for near-infrared and visible fluorescence imaging of tumor cell apoptosis both in vitro and in vivo.     

Novel isatin–indole derivatives as potential inhibitors of chorismate mutase (CM): their synthesis along with unexpected formation of 2-indolylmethylamino benzoate ester under Pd–Cu catalysis

A series of novel isatin–indole derivatives has been designed as potential inhibitors of chorismate mutase (CM) that is known to be present in bacteria, fungi and higher plants but not in human. The design was supported by in silico docking studies that predicted strong interactions of these molecules with CM. The target compounds were synthesized via the one-pot coupling/cyclization method involving the reaction of an isatin based terminal alkyne with 2-iodosulfanilides under Pd–Cu catalysis. A number of isatin–indole derivatives were prepared using this method. A side product e.g. 2-indolylmethylamino benzoate ester derivative was obtained as a result of isatin ring opening (ethanolysis) of products in certain cases. Additionally, regioselective reduction of selected compounds afforded the corresponding C-3 hydroxy derivatives. All isatin–indole derivatives showed good to high inhibition of CM in vitro among which two compounds (3e and 3f) showed inhibition at nanomolar concentration.

Design, synthesis and evaluation of isatin–indole derivatives were undertaken to identify potent inhibitors of chorismate mutase.     

Therapeutic polymeric nanomedicine: GSH-responsive release promotes drug release for cancer synergistic chemotherapy

To obtain an efficient dual-drug release and enhance therapeutic efficiency for combination chemotherapy, a glutathione (GSH)-responsive therapeutic amphiphilic polyprodrug copolymer (mPEG-b-PCPT) is synthesized to load doxorubicin (DOX) via hydrophobic and π–π stacking interaction. In this nanomedicine system (mPEG-b-PCPT/DOX), the ratio of the two drugs can be easily modulated by changing the loading content of DOX. The in vitro drug release curves and laser confocal images suggested that the release of CPT and DOX is induced through a “release promotes release strategy”: after internalization into tumor cells, the disulfide bonds in the nanomedicine are cleaved by glutathione (GSH) in the cytoplasm and then lead to the release of CPT. Meanwhile, the disassembly of nanomedicine immediately promotes the co-release of DOX. The optimum dose ratio of CPT and DOX is evaluated via the combination index (CI) value using HepG-2 cells. The results of cell apoptosis and cell viability prove the better synergistic efficiency of the nanomedicine than free drugs at the optimum dose ratio of 1. Consequently, this stimuli-responsive synergistic chemotherapy system provides a direction for the fabrication of nanomedicines possessing promising potential in clinical trials.

In the GSH-responsive doxorubicin loading camptothecin prodrug nanomedicine, easy modulation of the dose ratio and controlled co-release were achieved, and the synergistic effect was significantly improved.     

Hyperelatosides A–E,biphenyl ether glycosides from Hypericum elatoides,with neurotrophic activity

Five new biphenyl ether glycosides, hyperelatosides A–E (1–5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7–15), were isolated from the aerial parts of Hypericum elatoides. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed. Except for 3, the new phenolic metabolites exhibited significant neurotrophic activities to enhance nerve growth factor-induced neurite outgrowth in PC12 cells. In addition, the anti-neuroinflammatory and antioxidant activities of compounds 1–15 were preliminarily evaluated in vitro.

Five new biphenyl ether glycosides, hyperelatosides A–E, one new benzoate glycoside, hyperelatoside F, were isolated from Hypericum elatoides. Hyperelatosides A, B, and D–F significantly enhanced NGF-induced neurite outgrowth in PC12 cells.     

Palladium mediated domino reaction: synthesis of isochromenes under aqueous medium

Isochromenes have been synthesized using palladium-catalyzed C–C and C–O bond forming reactions starting from ortho-bromo tertiary benzylic alcohols and internal acetylenes. Notably, this domino process is feasible by using the green solvent, water. The protocol exhibited a broad substrate scope and afforded various isochromenes.

Isochromenes have been synthesized using palladium-catalyzed C–C and C–O bond forming reactions starting from ortho-bromo tertiary benzylic alcohols and internal acetylenes.     

Sulfadiazine hosted in MIL-53(Al) as a biocide topical delivery system

Sulfadiazine (SDZ), a bacteriostatic agent, was hosted in a metal–organic framework, specifically in MIL-53(Al) and modified-zinc MIL-53(Al,Zn). Materials were characterized structural, and texturally. Both hosts loaded sulfadiazine but they were differenced regarding the release of sulfadiazine. The presence of zinc plays a significant role to the modulation of sulfadiazine–MOF interactions. Release of sulfadiazine from sulfadiazine@MOFs was monitored in vitro and ex vivo conditions. A kinetic release model is proposed for in vitro sulfadiazine release. Remarkably, the materials did not show cytotoxicity against eukaryote cells.

Sulfadiazine (SDZ), a bacteriostatic agent, was hosted in MIL-53(Al) and modified-zinc MIL-53(Al,Zn).     

Correction: Theoretical calculation of a full-dimensional ab initio potential energy surface and prediction of infrared spectra for Xe–CS2

Correction for ‘Theoretical calculation of a full-dimensional ab initio potential energy surface and prediction of infrared spectra for Xe–CS₂’ by Miao Qin et al., RSC Adv., 2019, 9, 20925–20930.

The authors regret that eqn (4) was displayed incorrectly in the PDF version of the original article. The correct version of eqn (4) is presented below:The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Spontaneous alloying of ultrasmall non-stoichiometric Ag–In–S and Cu–In–S quantum dots in aqueous colloidal solutions

The effect of spontaneous alloying of non-stoichiometric aqueous Ag–In–S (AIS) and Cu–In–S (CIS) quantum dots (QDs) stabilized by surface glutathione (GSH) complexes was observed spectroscopically due to the phenomenon of band bowing typical for the solid–solution Cu(Ag)–In–S (CAIS) QDs. The alloying was found to occur even at room temperature and can be accelerated by a thermal treatment of colloidal mixtures at around 90 °C with no appreciable differences in the average size observed between alloyed and original individual QDs. An equilibrium between QDs and molecular and clustered metal–GSH complexes, which can serve as “building material” for the new mixed CAIS QDs, during the spontaneous alloying is assumed to be responsible for this behavior of GSH-capped ternary QDs. The alloying effect is expected to be of a general character for different In-based ternary chalcogenides.

The effect of spontaneous alloying of aqueous glutathione-capped Ag–In–S and Cu–In–S quantum dots (QDs) into quaternary Cu(Ag)–In–S QDs is reported.     

An ultrasensitive colorimetric and fluorescence dual-readout assay for glutathione with a carbon dot–MnO2 nanosheet platform based on the inner filter effect

An ultrasensitive colorimetric and fluorescence dual-readout assay based on the inner filter effect (IFE) was developed for glutathione (GSH) determination, in which carbon dots (C-dots) were used as a fluorophore and MnO₂ nanosheets as an absorber. Due to the excellent optical absorption properties of MnO₂ nanosheets and the good spectral overlap between the fluorophore and absorber, MnO₂ nanosheets could effectively quench the fluorescence of C-dots via the IFE. As the target, GSH could reduce MnO₂ nanosheets to Mn²⁺ ions, which inhibited the IFE and resulted in the fading of solution color and the recovery of the fluorescence signal. And these two kinds of signals were respectively used for qualitative and quantitative detection of GSH. The results showed that this proposed assay could distinguish 10 μM GSH with the naked eye and quantitatively detect GSH within the concentration range of 0.1–400 μM. The limit of detection was 6.6 nM. Moreover, this assay showed sensitive responses in human serum and urine samples, which indicated that this IFE-based assay has great potential in GSH-related clinical and bioanalytical applications.

An ultrasensitive colorimetric and fluorescence dual-readout assay based on carbon dot–MnO₂ nanosheets platform was developed for GSH detection in human body fluid samples.     

SWIR emissive RosIndolizine dyes with nanoencapsulation in water soluble dendrimers

Shortwave infrared (SWIR) emission has great potential for deep-tissue in vivo biological imaging with high resolution. In this article, the synthesis and characterization of two new xanthene-based RosIndolizine dyes coded ^PhRosIndz and ^tolRosIndz is presented. The dyes are characterized via femtosecond transient absorption spectroscopy as well as steady-state absorption and emission spectroscopies. The emission of these dyes is shown in the SWIR region with peak emission at 1097 nm. ^TolRosIndz was encapsulated with an amphiphilic linear dendritic block co-polymer (LDBC) coded 10-PhPCL-G3 with high uptake yield. Further, cellular toxicity was examined in vitro using HEK (human embryonic kidney) cells where a >90% cell viability was observed at practical concentrations of the encapsulated dye which indicates low toxicity and reasonable biocompatibility.

A xanthene–indolizine dye is shown to emit in the shortwave infrared spectral region (∼1100 nm maximum) in water when nanoencapsulated.     

Fabrication of hydroxyapatite coatings on AZ31 Mg alloy by micro-arc oxidation coupled with sol–gel treatment

Magnesium (Mg) alloys, can potentially be used as biodegradable orthopedic implants because of their biodegradability and good mechanical properties. However, a quick degradation rate and low bioactivity have prevented their clinical application. In order to enhance the corrosion resistance and the in vitro bioactivity of Mg alloys, protective composite coatings were prepared on AZ31 magnesium alloy followed by sol–gel sealing treatment under low-pressure conditions. The morphologies, crystalline structure and the composition of the samples were characterized by SEM, XRD, and XPS. Electrochemical corrosion test and the in vitro bioactivity were also studied. The results indicated that the composite coatings not only improved the corrosion resistance, but also enhanced the in vitro bioactivity of AZ31 Mg alloy. Therefore, Mg alloy treated with micro-arc oxidation and sol–gel offers a promising approach for biodegradable bone implants.

Magnesium (Mg) alloys, can potentially be used as biodegradable orthopedic implants because of their biodegradability and good mechanical properties.     

A novel carboxylic-functional indole-based aerogel for highly effective removal of heavy metals from aqueous solution via synergistic effects of face–point and point–point interactions

A new type of carboxylic-functional indole-based aerogel (CHIFA) has been successfully prepared via a facile sol–gel technology, which possessed a highly effective removal of heavy metals from aqueous solution through the synergistic effects of face–point and point–point interactions.

A new type of carboxylic-functional indole-based aerogel (CHIFA) has been successfully prepared, which possessed highly effective removal of heavy metals from aqueous solution through the synergistic effects of face–point and point–point interactions.