Study on synergistic mechanism of molybdenum disulfide/sodium carboxymethyl cellulose composite nanofiber mats for photothermal/photodynamic antibacterial treatment.

Innovative antibacterial therapies using nanomaterials, such as photothermal (PTT) and photodynamic (PDT) treatments, have been developed for treating wound infections. However, creating secure wound dressings with these therapies faces challenges. The primary focus of this study is to prepare an antibacterial nanofiber dressing that effectively incorporates stable loads of functional nanoparticles and demonstrates an efficient synergistic effect between PTT and PDT. Herein, a composite nanofiber mat was fabricated, integrating spherical molybdenum disulfide (MoS2) nanoparticles. MoS2 was deposited onto polylactic acid (PLA) nanofiber mats using vacuum filtration, which was further stabilized by sodium carboxymethyl cellulose (CMC) adhesion and glutaraldehyde (GA) cross-linking. The composite nanofibers demonstrated synergistic antibacterial effects under NIR light irradiation, and the underlying mechanism was explored. They induce bacterial membrane permeability, protein leakage, and intracellular reactive oxygen species (ROS) elevation, ultimately leading to >95 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which is higher than that of single thermotherapy (almost no antibacterial activity) or ROS therapy (about 80 %). In addition, the composite nanofiber mats exhibited promotion effects on infected wound healing in vivo. This study demonstrates the great prospects of composite nanofiber dressings in clinical treatment of bacterial-infected wounds.

Significance of the Disulfide Bridge in the Structure and Stability of Metalloprotein Azurin.

Metalloproteins make up a class of proteins that incorporate metal ions into their structures, enabling them to perform essential functions in biological systems, such as catalysis and electron transport. Azurin is one such metalloprotein with copper cofactor, having a ß-barrel structure with exceptional thermal stability. The copper metal ion is coordinated at one end of the ß-barrel structure, and there is a disulfide bond at the opposite end. In this study, we explore the effect of this disulfide bond in the high thermal stability of azurin by analyzing both the native S-S bonded and S-S nonbonded (S-S open) forms using temperature replica exchange molecular dynamics (REMD). Similar to experimental observations, we find a 35 K decrease in denaturation temperature for S-S open azurin compared to that of the native holo form (420 K). As observed in the case of native holo azurin, the unfolding process of the S-S open form also started with disruptions of the α-helix. The free energy surfaces of the unfolding process revealed that the denaturation event of the S-S open form progresses through different sets of conformational ensembles. Subsequently, we compared the stabilities of individual ß-sheet strands of both the S-S bonded and the S-S nonbonded forms of azurin. Further, we examined the contacts between individual residues for the central structures from the free energy surfaces of the S-S nonbonded form. The microscopic origin of the lowering in the denaturation temperature is further supplemented by thermodynamic analysis.

Novel Chemo-Photothermal Therapy in Hepatic Cancer Using Gemcitabine-Loaded Hyaluronic Acid Conjugated MoS2/ZnO Nanocomposites.

Hepatocellular carcinoma is a serious illness with a high rate of mortality. A high dose of theranostic drugs with efficient diagnostic and therapeutic capabilities should be required. Chemo-photothermal therapy is presently recognized as a secure method of cancer treatment that specifically targets tumour tissue or cells. Additionally, the success of cancer therapy is increased by the use of targeted nanoparticles. The current study aims to investigate the interaction between phototherapy and the anti-hepatocellular carcinoma treatment combination HA-GEM-MoS2/ZnO nanocomposites (NCs) loaded with gemcitabine and molybdenum disulphide. NCs were synthesized and characterized using FT-IR, XRD, TEM, and DLS analyses. The present investigation shows that the synthesized HA-MoS2/ZnO nanocomposites were elongated spherical in shape and their sizes ranged from 62.3 to 75.7 nm according to the estimation using XRD results, which is consistent with TEM findings. Further, HA-MoS2/ZnO nanocomposites could effectively encapsulate the GEM, showing dual pH and thermal triggered drug release behaviour. The result of cell uptake tests clearly demonstrated improved cellular uptake of synthesized nanocomposites following HA and GEM-loaded NCs in hepatocellular carcinoma cell lines. In addition, combination therapies caused the highest incidence of cell death in hepatocellular carcinoma, according to cytotoxicity experiments and showed a good compatibility. In vitro studies prove that HA-GEM-MoS2/ZnO nanocomposites enhanced tumour treatment that combines chemotherapy and photothermal therapy to remove the tumour and prevent relapses. Still, no studies have been done to see if gemcitabine-encapsulated HA-MoS2/ZnO NCs inhibit human hepatocellular carcinoma cell. Hence, the current study can give a new paradigm for the diagnosis and treatment of cancer and the outcome may be helpful to improve the quality of cancer patient's life.

pH-responsive in situ gelling properties of thiolated citrus high-methoxyl pectin and its potential gel mechanism.

pH-responsive in situ gelling properties of thiolated citrus high-methoxyl pectin (TCHMP) were investigated in this study. The gelation capacity results revealed that the in situ gelation behavior of TCHMP only occurred when the pH value was higher than 6.25. The gel strength increased from 26.63 g to 42.77 g as the pH value increased from 7.4 to 8.9. Rheological measurements confirmed that the apparent viscosity and viscoelasticity of TCHMP were highly dependent on pH value and dialysis time. Compared with the control group, the apparent viscosity of TCHMP dialyzed in phosphate-buffered saline (PBS) of pH 8.9 for 180 min increased 695-fold. During the dialysis process of TCHMP at different pH values (7.4-8.9), the final thiol groups content decreased and the final disulfide bonds content increased with the increase in pH value. This illustrates that the mechanism of in situ gelation is mainly the oxidation of thiol-thiol groups to form disulfide bonds. These results can put forward new insights into the pH-responsive in situ gelling properties of TCHMP and provide a theoretical basis for the application of TCHMP in neutral and alkaline gel systems.

Activity-Based Proteomic Identification of the S-Thiolation Targets of Ajoene in MDA-MB-231 Breast Cancer Cells.

Garlic is a medicinal plant and spice that has been used for millennia for its health-promoting effects. These medicinal properties are associated with low molecular weight organosulfur compounds, produced following the crushing of garlic cloves. One of these compounds, ajoene, is proposed to act by S-thioallylating cysteine residues on target proteins whose identification in cancer cells holds great promise for understanding mechanistic aspects of ajoene's cancer cell cytotoxicity. To this end, an ajoene analogue (called biotin-ajoene, BA), containing a biotin affinity tag, was designed as an activity-based probe specific for the protein targets of ajoene in MDA-MB-231 breast cancer cells. BA was synthesized via a convergent "click" strategy and found to retain its cytotoxicity against MDA-MB-231 cells compared to ajoene. Widespread biotinylation of proteins was found to occur via disulfide bond formation in a dose-dependent manner, and the biotin-ajoene probe was found to share the same protein targets as its parent compound, ajoene. The biotinylated proteins were affinity-purified from the treated MDA-MB-231 cell lysate using streptavidin-coated magnetic beads followed by an on-bead reduction, alkylation, and digestion to liberate the peptide fragments, which were analyzed by liquid chromatography tandem mass chromatography. A total of 600 protein targets were identified, among which 91% overlapped with proteins with known protein cysteine modification (PCM) sites. The specific sites were enriched for those susceptible to S-glutathionylation (-SSG) (16%), S-sulfhydration (-SSH) (20%), S-sulfenylation (-SOH) (22%), and S-nitrosylation (-SNO) (31%). As target validation, both ajoene and a dansylated ajoene (DP) were found to S-thiolate the pure recombinant forms of glutathione S-transferase pi 1 (GSTP1) and protein disulfide isomerase (PDI), and the ajoene analogue DP was found to be a more potent inhibitor than 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB). Pathway analysis elucidated that ajoene targets functional and signaling pathways that are implicated in cancer cell survival, specifically cellular processes, metabolism, and genetic information processing pathways. The results of this study provide mechanistic insights into the character of the anti-cancer activity of the natural dietary compound ajoene.

Influence of mild oxidation induced through DBD-plasma treatment on the structure and gelling properties of glycinin.

The effects of dielectric-barrier discharge (DBD) plasma treatment (20 s to 120 s treatment time with 40 kV, 12 kHz) induced mild oxidation on the gelling properties, and related structural changes of glycinin were investigated. The gelling ability of glycinin was improved by the mild oxidation induced by the plasma treatment. Treated glycinin gels exhibited a continuous and uniform network microstructure. Samples treated for 120 s had a 2.07-, 3.99- and 2.03-fold increase in hardness, chewiness, and resilience compared to the 20 s treated samples. Structural analyses showed that primary and secondary structures of glycinin were unaffected. The tertiary structure was shifted, accompanied by a decrease in free sulfhydryl (-SH) content. At the same time, carbonyl content and average particle diameter were increased by DBD treatment. The DBD treatment facilitated the generation/exchange of intermolecular disulfide bonds and enhanced gelling properties of glycinin. It is concluded that controlled plasma-induced protein oxidation can improve protein functionality.

Rational assembly of RGD/MoS2/Doxorubicin nanodrug for targeted drug delivery, GSH-stimulus release and chemo-photothermal synergistic antitumor activity.

Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity. MoS2 nanosheets were synthesized and modified by ανß3 integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier. Further, covalent coupling of antitumor drug, thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS2/DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment. The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.

2D Molybdenum Sulfide-Based Materials for Photo-Excited Antibacterial Application.

Bacterial infections have seriously threatened human health and the abuse of natural or artificial antibiotics leads to bacterial resistance, so development of a new generation of antibacterial agents and treatment methods is urgent. 2D molybdenum sulfide (MoS2 ) has good biocompatibility, high specific surface area to facilitate surface modification and drug loading, adjustable energy bandgap, and high near-infrared photothermal conversion efficiency (PCE), so it is often used for antibacterial application through its photothermal or photodynamic effects. This review comprehensively summarizes and discusses the fabrication processes, structural characteristics, antibacterial performance, and the corresponding mechanisms of MoS2 -based materials as well as their representative antibacterial applications. In addition, the outlooks on the remaining challenges that should be addressed in the field of MoS2 are also proposed.

Interaction of Periplasmic Fab Production and Intracellular Redox Balance in Escherichia coli Affects Product Yield.

Antibody fragments such as Fab's require the formation of disulfide bonds to achieve a proper folding state. During their recombinant, periplasmic expression in Escherichia coli, oxidative folding is mediated by the DsbA/DsbB system in concert with ubiquinone. Thereby, overexpression of Fab's is linked to the respiratory chain, which is not only immensely important for the cell's energy household but also known as a major source of reactive oxygen species. However, the effects of an increased oxidative folding demand and the consequently required electron flux via ubiquinone on the host cell have not been characterized so far. Here, we show that Fab expression in E. coli BL21(DE3) interfered with the intracellular redox balance, thereby negatively impacting host cell performance. Production of four different model Fab's in lab-scale fed-batch cultivations led to increased oxygen consumption rates and strong cell lysis. An RNA sequencing analysis revealed transcription activation of the oxidative stress-responsive soxS gene in the Fab-producing strains. We attributed this to the accumulation of intracellular superoxide, which was measured using flow cytometry. An exogenously supplemented ubiquinone analogue improved Fab yields up to 82%, indicating that partitioning of the quinone pool between aerobic respiration and oxidative folding limited ubiquinone availability and hence disulfide bond formation capacity. Combined, our results provide a more in-depth understanding of the profound effects that periplasmic Fab expression and in particular disulfide bond formation has on the host cell. Thereby, we show new possibilities to elaborate cell engineering and process strategies for improved host cell fitness and process outcome.

In situ grown bacterial cellulose/MoS2 composites for multi-contaminant wastewater treatment and bacteria inactivation.

For the purpose of developing multifunctional water purification materials capable of degrading organic pollutants while simultaneously inactivating microorganisms from contaminated wastewater streams, we report here a facile and eco-friendly method to immobilize molybdenum disulfide into bacterial cellulose via a one-step in-situ biosynthetic method. The resultant nanocomposite, termed BC/MoS2, was shown to possess a photocatalytic activity capable of generating •OH from H2O2, while also exhibiting photodynamic/photothermal mechanisms, the combination of which exhibits synergistic activity for the degradation of pollutants as well as for bacterial inactivation. In the presence of H2O2, the BC/MoS2 nanocomposite exhibited excellent antibacterial efficacy upwards of 99.9999% (6 log units) for the photoinactivation of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus upon infrared (IR) lamp illumination (100 W, 760 nm ≤ λ ≤ 5000 nm, 15 cm vertical distance; 5 min). Mechanistic studies revealed synergistic pathogen inactivation resulting from the combination of photocatalytically generated •OH and hyperthermia induced by the photothermal conversion of the near-IR light. In addition, the BC/MoS2 nanocomposite also showed excellent photodegradation activity for common aqueous contaminants in the presence of H2O2, including malachite green (a textile dye), catechol violet (a phenol) and formaldehyde. Taken together, our findings demonstrate that sustainable materials such as BC/MoS2 have potential applications in wastewater treatment and microorganism disinfection.

Effect of Al2O3 Passive Layer on Stability and Doping of MoS2 Field-Effect Transistor (FET) Biosensors.

Molybdenum disulfide (MoS2) features a band gap of 1.3 eV (indirect) to 1.9 eV (direct). This tunable band gap renders MoS2 a suitable conducting channel for field-effect transistors (FETs). In addition, the highly sensitive surface potential in MoS2 layers allows the feasibility of FET applications in biosensors, where direct immobilization and detection of biological molecules are conducted in wet conditions. In this work, we report, for the first time, the degradation of chemical vapor deposition (CVD) grown MoS2 FET-based sensors in the presence of phosphate buffer and water, which caused false positive response in detection. We conclude the degradation was originated by physical delamination of MoS2 thin films from the SiO2 substrate. The problem was alleviated by coating the sensors with a 30 nm thick aluminum oxide (Al2O3) layer using atomic layer deposition technique (ALD). This passive oxide thin film not only acted as a protecting layer against the device degradation but also induced a strong n-doping onto MoS2, which permitted a facile method of detection in MoS2 FET-based sensors using a low-power mode chemiresistive I-V measurement at zero gate voltage (Vgate = 0 V). Additionally, the oxide layer provided available sites for facile functionalization with bioreceptors. As immunoreaction plays a key role in clinical diagnosis and environmental analysis, our work presented a promising application using such enhanced Al2O3-coated MoS2 chemiresistive biosensors for detection of HIgG with high sensitivity and selectivity. The biosensor was successfully applied to detect HIgG in artificial urine, a complex matrix containing organics and salts.

Mitochondria-Targeting MoS2-Based Nanoagents for Enhanced NIR-II Photothermal-Chemodynamic Synergistic Oncotherapy.

The synergy of chemodynamic therapy (CDT) and photothermal therapy (PTT) can improve anticancer efficacy, while the limited diffusion distance and the short lifetime of •OH still greatly restrict the therapeutic efficacy of PTT-CDT. Herein, MoS2@PDA-Fe@PEG/TPP (MPFPT) nanosheets (NSs) with mitochondria-targeting ability were reported for enhanced PTT-CDT synergistic oncotherapy. MPFPT NSs were prepared by covalent modification of poly(ethylene glycol) (PEG) and triphenylphosphonium (TPP) on polydopamine (PDA)-Fe3+coated MoS2 NSs. Co-localization experiments showed that MPFPT NSs can efficiently target mitochondria via the direction of TPP. Moreover, MPFPT NSs have good photothermal performance in the second near-infrared (NIR-II) region and can greatly accelerate the Fenton reaction from H2O2 to generate more hydroxyl radicals (•OH). In vitro experimental results showed that MPFPT NSs have improved therapeutic efficacy to cancer cells than similar MoS2-based nanoagents without mitochondria-targeting units, which can be attributed to the short distance between mitochondria and MPFPT NSs and the efficient damage of mitochondria by in situ generated •OH. In the 4T1 tumor-bearing mice model, MPFPT NSs demonstrated significantly enhanced therapeutic efficacy by PTT-CDT, suggesting the superiority of the mitochondria-targeting strategy. This study reveals that mitochondria-targeting MPFPT NSs are promising nanoagents for oncotherapy.

Copper(II)-mediated C-H sulphenylation or selenylation of tryptophan enabling macrocyclization of peptides.

Cu(II)-mediated C-H sulphenylation or selenylation of Trp indole by a derivative of cysteine or selenocysteine enables access to the tryptathionine unit or its selenium congener. The mechanism of these protocols, which allow macrocyclization of Trp-containing peptides, has been studied.

Membrane interaction and disulphide-bridge formation in the unconventional secretion of Tau.

Misfolded, pathological tau protein propagates from cell to cell causing neuronal degeneration in Alzheimer's disease and other tauopathies. The molecular mechanisms of this process have remained elusive. Unconventional secretion of tau takes place via several different routes, including direct penetration through the plasma membrane. Here, we show that tau secretion requires membrane interaction via disulphide bridge formation. Mutating residues that reduce tau interaction with membranes or formation of disulphide bridges decrease both tau secretion from cells, and penetration through artificial lipid membranes. Our results demonstrate that tau is indeed able to penetrate protein-free membranes in a process independent of active cellular processes and that both membrane interaction and disulphide bridge formation are needed for this process. QUARK-based de novo modelling of the second and third microtubule-binding repeat domains (MTBDs), in which the two cysteine residues of 4R isoforms of tau are located, supports the concept that this region of tau could form transient amphipathic helices for membrane interaction.

Targeting acute myeloid leukemia cells by CD33 receptor-specific MoS2-based nanoconjugates.

Acute myeloid leukemia (AML) is a highly aggressive type of cancer caused by the uncontrolled proliferation of undifferentiated myeloblasts, affecting the bone marrow and blood. Systemic chemotherapy is considered the primary treatment strategy; unfortunately, healthy cells are also affected to a large extent, leading to severe side effects of this treatment. Targeted drug therapies are becoming increasingly popular in modern medicine, as they bypass normal tissues and cells. Two-dimensional MoS2-based nanomaterials have attracted attention in the biomedical field as promising agents for cancer diagnosis and therapy. Cancer cells typically (over)express distinctive cytoplasmic membrane-anchored or -spanning protein-based structures (e.g., receptors, enzymes) that distinguish them from healthy, non-cancerous cells. Targeting cancer cells via tumor-specific markers using MoS2-based nanocarriers loaded with labels or drugs can significantly improve specificity and reduce side effects of such treatment. SKM-1 is an established AML cell line that has been employed in various bio-research applications. However, to date, it has not been used as the subject of studies on selective cancer targeting by inorganic nanomaterials. Here, we demonstrate an efficient targeting of AML cells using MoS2nanoflakes prepared by a facile exfoliation route and functionalized with anti-CD33 antibody that binds to CD33 receptors expressed by SKM-1 cells. Microscopic analyses by confocal laser scanning microscopy supplemented by label-free confocal Raman microscopy proved that (anti-CD33)-MoS2conjugates were present on the cell surface and within SKM-1 cells, presumably having been internalized via CD33-mediated endocytosis. Furthermore, the cellular uptake of SKM-1 specific (anti-CD33)-MoS2conjugates assessed by flow cytometry analysis was significantly higher compared with the cellular uptake of SKM-1 nonspecific (anti-GPC3)-MoS2conjugates. Our results indicate the importance of appropriate functionalization of MoS2nanomaterials by tumor-recognizing elements that significantly increase their specificity and hence suggest the utilization of MoS2-based nanomaterials in the diagnosis and therapy of AML.

Improved Protein and PTM Characterization with a Practical Electron-Based Fragmentation on Q-TOF Instruments.

Electron-based dissociation (ExD) produces uncluttered mass spectra of intact proteins while preserving labile post-translational modifications. However, technical challenges have limited this option to only a few high-end mass spectrometers. We have developed an efficient ExD cell that can be retrofitted in less than an hour into current LC/Q-TOF instruments. Supporting software has been developed to acquire, process, and annotate peptide and protein ExD fragmentation spectra. In addition to producing complementary fragmentation, ExD spectra enable many isobaric leucine/isoleucine and isoaspartate/aspartate pairs to be distinguished by side-chain fragmentation. The ExD cell preserves phosphorylation and glycosylation modifications. It also fragments longer peptides more efficiently to reveal signaling cross-talk between multiple post-translational modifications on the same protein chain and cleaves disulfide bonds in cystine knotted proteins and intact antibodies. The ability of the ExD cell to combine collisional activation with electron fragmentation enables more complete sequence coverage by disrupting intramolecular electrostatic interactions that can hold fragments of large peptides and proteins together. These enhanced capabilities made possible by the ExD cell expand the size of peptides and proteins that can be analyzed as well as the analytical certainty of characterizing their post-translational modifications.

Effect of physicochemical parameters on the stability and activity of garlic alliinase and its use for in-situ allicin synthesis.

Garlic is a well-known example of natural self-defence system consisting of an inactive substrate (alliin) and enzyme (alliinase) which, when combined, produce highly antimicrobial allicin. Increase of alliinase stability and its activity are of paramount importance in various applications relying on its use for in-situ synthesis of allicin or its analogues, e.g., pulmonary drug delivery, treatment of superficial injuries, or urease inhibitors in fertilizers. Here, we discuss the effect of temperature, pH, buffers, salts, and additives, i.e. antioxidants, chelating agents, reducing agents and cosolvents, on the stability and the activity of alliinase extracted from garlic. The effects of the storage temperature and relative humidity on the stability of lyophilized alliinase was demonstrated. A combination of the short half-life, high reactivity and non-specificity to particular proteins are reasons most bacteria cannot deal with allicin's mode of action and develop effective defence mechanism, which could be the key to sustainable drug design addressing serious problems with escalating emergence of multidrug-resistant (MDR) bacterial strains.

Modification of magnetic molybdenum disulfide by chitosan/carboxymethylcellulose with enhanced dispersibility for targeted photothermal-/chemotherapy of cancer.

In this work, magnetic molybdenum disulfide (mMoS2) was synthesized firstly. Then, layer-by-layer (LbL) self-assembly technology was used for the preparation of chitosan/carboxymethylcellulose functionalized mMoS2 nanocomposites. The nanocomposites with the diameter of 0.4 µm did not easily agglomerate in biological suspensions, thus had good dispersion and stability. Simultaneously, mMoS2-CS/CMC strongly inhibited the adsorption of non-specific proteins to mMoS2. In a drug loading experiment, in which doxorubicin hydrochloride (DOX) was used as a model drug, it was found that the drug loading capacity of mMoS2-CS/CMC was high and the drug loading rate could reach 86%. When the drug was released, mMoS2-CS/CMC-DOX showed an obvious pH-dependent release behavior. In cellular studies, the nanocomposites were easily taken up by tumor cells, and mainly located in the cytoplasm. The pure carrier materials had good biocompatibility with no obvious cytotoxicity, but they could cause dose-dependent cytotoxicity after DOX loading. Moreover, mMoS2-CS/CMC had an excellent photothermal effect, and an in vivo study showed that after it was injected into mice, more nanocomposites concentrated in the tumor site than mMoS2, indicating the tumor targeting properties. Therefore, the modification of mMoS2 with chitosan and sodium carboxymethylcellulose will promote the development of tumor therapy.

Enhanced Photothermal-Photodynamic Therapy by Indocyanine Green and Curcumin-Loaded Layered MoS2 Hollow Spheres via Inhibition of P-Glycoprotein.

PURPOSE: P-glycoprotein (P-gp), which is highly expressed in liver cancer cells, is one of the obstacles for the treatment of cancer. In this study, we have prepared and characterized a kind of novel ICG&Cur@MoS2 (ICG and Cur represent indocyanine green and curcumin, respectively) nanoplatform, which can achieve photothermal-photodynamic therapy and inhibit the P-gp effectively and safely. METHODS: In this work, plenty of studies including drug release, acute toxicity, Western blot, real-time PCR, cell viability, therapeutic experiment in vivo, immunofluorescence and so on were conducted to test the antitumor potential of ICG&Cur@MoS2 and the inhibitory effect of curcumin on P-gp. RESULTS: The ICG&Cur@MoS2 NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS2 + NIR group was significantly lower than that in ICG@MoS2 + NIR group (75.3% vs 81.2%, 59.0% vs 64.4%, 20.3% vs 27.5%, and 15.4% vs 22.3%) at the concentration of ICG at 0.5, 5, 25, 50 µg/mL (P<0.05 at each concentration). Western blot, Q-PCR, and immunofluorescence assay indicate ICG&Cur@MoS2 NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS2 + NIR group are significantly smaller than those in the MoS2 + NIR group (95.0 vs 420.9 mm3, p<0.05). CONCLUSION: In conclusion, we have successfully synthesized ICG&Cur@MoS2 nanoparticles which can not only achieve PTT-PDT but also inhibit P-gp effectively. Our findings indicate that the PTT-PDT exhibits great potential in the treatment of hepatocellular carcinoma. Meanwhile, ICG&Cur@MoS2 can effectively inhibit the expression of P-gp, which will enhance the PDT effect.

Light-assisted therapy for biofilm infected micro-arc oxidation TiO2 coating on bone implants.

Implant-associated infections is a main factor leading to the failure of titanium (Ti) implants. Micro-arc oxidation is a convenient and effective technique to form a biocompatible metal (Ag+, Cu2+ and Zn2+) ions-doped TiO2 coatings to combat bacterial infections. However, compared with the sterilization by metal ions, light-triggered antibacterial therapies have accepted more attention due to its higher antibacterial efficiency and security. Although TiO2 is an excellent photocatalyst, it can be triggered by ultraviolet light due to the wide band gap. Herein, molybdenum disulfide (MoS2) modified TiO2 coating was fabricated on Ti by a hybrid process of micro-arc oxidation and hydrothermal treatment. The hybrid coating exhibits excellent antibacterial activity under the irradiation of 808 nm near-infrared light because of the synergistic antibacterial effects of reactive oxygen species and hyperthermia, and Staphylococcus aureus (S. aureus) biofilm can be eradicated within 15 min both in vivo and in vitro. Furthermore, collagen decorated on the surface of the hybrid coating can improve the proliferation, adhesion and spreading of MC3T3-E1 osteoblasts.