Preparation, Characterization and Molecular Dynamics Simulation of Rutin-Cyclodextrin Inclusion Complexes.

Rutin is a natural flavonoid that carries out a variety of biological activities, but its application in medicine and food is limited by its water solubility. One of the classical methods used to enhance drug solubility is encapsulation with cyclodextrins. In this paper, the encapsulation of different cyclodextrins with rutin was investigated using a combination of experimental and simulation methods. Three inclusions of rutin/beta-cyclodextrin (ß-CD), rutin/2-hydroxypropyl beta-cyclodextrin (HP-ß-CD) and rutin/2,6-dimethyl beta-cyclodextrin (DM-ß-CD) were prepared by the freeze-drying method, and the inclusions were analyzed using Fourier infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC) and ultraviolet-visible spectroscopy (UV) to characterize and demonstrate the formation of the inclusion complexes. Phase solubility studies showed that rutin formed a 1:1 stoichiometric inclusion complex and significantly increased its solubility. ß-CD, HP-ß-CD, DM-ß-CD, rutin and the three inclusion complexes were modeled by using MS2018 and AutoDock 4.0, and molecular dynamics simulations were performed to calculate the solubility parameters, binding energies, mean square displacement (MSD), hydrogen bonding and radial distribution functions (RDF) after the equilibration of the systems. The results of simulation and experiment showed that rutin/DM-ß-CD had the best encapsulation effect among the three cyclodextrin inclusion complexes.

Evaluating the effects of hydrophobic and cationic residues on antimicrobial peptide self-assembly.

Antimicrobial peptides typically contain hydrophobic and cationic residues, which allow them to interact with microbial cells and induce cell death. In a previous study, we found that the hydrophobic and cationic residues could also help antimicrobial peptides self-assemble into hydrogels, and this could be used as a novel approach for the preparation of hydrogel wound dressings. Therefore, in this work, four PAF26 peptide derivatives with different hydrophobic and cationic residues were used to study the effects of hydrophobic and cationic residues on self-assembly behaviours. It was found that all the PAF26 peptide derivatives could self-assemble into hydrogels, but the storage moduli, microscopic structures, secondary structure transformations, and antimicrobial abilities varied. In particular, peptides with a greater number of hydrophobic and cationic residues tended to undergo an unordered coil transformation and form bent nanofibers, while peptides with a lower number of hydrophobic and cationic residues tended to undergo ß-sheet transformation and form straight nanofibers. In addition, antimicrobial experiments demonstrated that a strong crosslinked structure may have negative effects on the antimicrobial activity.

HPO42- enhanced catalytic activity of N, S, B, and O-codoped carbon nanosphere-armored Co9S8 nanoparticles for organic pollutants degradation via peroxymonosulfate activation: critical roles of superoxide radical, singlet oxygen and electron transfer.

In this study, we report a facile synthesis of a novel N, S, B, and O-codoped carbon nanosphere-armored Co9S8 nanoparticle composite (Co9S8@NSBOC) and its superior activation performance toward peroxymonosulfate (PMS) for methylene blue (MB) and ofloxacin degradation. The effects of various experimental parameters and the general applicability of the catalyst were investigated. Particularly, Co9S8@NSBOC exhibited high catalytic activity in a wide pH range of 3-12 and HPO42- exhibited a synergic catalytic effect with Co9S8@NSBOC in the degradation system. Radical quenching tests, EPR measurements and electrochemical analysis demonstrated that the degradation mechanism of pollutants in the Co9S8@NSBOC/PMS system included both radical and non-radical pathways, in which ˙O2-, 1O2 and electron transfer played dominant roles. Co2+, S2-, carbon defects, C[double bond, length as m-dash]O/C-O-C, pyridinic-N, graphitic-N, BC2O and C-S-C species on Co9S8@NSBOC, all contributed to PMS activation. The degradation pathways of MB and ofloxacin were proposed based on HPLC-MS/MS analysis of their degradation intermediates. This work not only presents a facile and practical synthetic method of cobalt sulfide-coupled multi-heteroatom-doped carbocatalysts, but also provides useful insights into their active sites and activation mechanisms toward PMS activation.

Co nanoparticle-embedded N,O-codoped porous carbon nanospheres as an efficient peroxymonosulfate activator: singlet oxygen dominated catalytic degradation of organic pollutants.

In this study, Co nanoparticle-embedded N,O-codoped porous carbon nanospheres (C@Co) with abundant N and O doping, high graphitization, large specific surface area (319 m2 g-1) and a well-developed mesoporous structure were synthesized and characterized thoroughly, and were applied to activate peroxymonosulfate (PMS) for the degradation of methylene blue (MB). Various influential factors affecting the catalytic performance including C@Co dosage, PMS dosage, MB concentration, initial pH, temperature, and co-existing common anions and humic acid (HA) on the MB degradation were systematically investigated. The increase of the C@Co dosage (15-60 mg), PMS dosage (25-100 mg) and reaction temperature (278-308 K) promoted the MB degradation in the C@Co/PMS system. The best performance of the C@Co/PMS system was observed under weakly acidic or nearly neutral conditions. Both the MB concentration (25-100 mg L-1) and Cl- (5-100 mM), NO3- (10-500 mM), CO32- (10-300 mM), HCO3- (1-30 mM) and HA (2-40 mg L-1) had an inhibitory effect on MB degradation, and the degree of decrease in MB degradation increased as their concentrations were enhanced. Interestingly, HPO42- (1-100 mM) had an overall inhibitory effect on the degradation process of MB; however, in comparison with lower concentrations (1-10 mM), an attenuation of the inhibitory effect at higher concentrations (50-100 mM) could be observed. Moreover, the C@Co/PMS system also exhibited general applicability in eliminating various organic pollutants from water such as methyl orange, malachite green, safranine T, Congo red, Rhodamine B, ofloxacin and tetracycline. Classical radical-quenching tests and EPR measurements showed that both the non-radical pathway (major route, involving 1O2) and radical pathway (minor route, involving ˙OH, ˙SO4- and ˙O2-) contribute to the MB degradation. DFT calculations disclosed that the combination of Co-C interactions with graphitic N doping brought in catalytically active sites in C@Co where the charge states of some C atoms were significantly increased. The degradation intermediates of MB during the catalytic reaction were also identified by HPLC-MS and the possible degradation pathway was proposed. Overall, the resultant C@Co can be developed as a novel and efficient heterogeneous catalyst for activating PMS to degrade organic pollutants, and has potential application in environmental remediation.

A smart fluorescence nanoprobe for the detection of cellular alkaline phosphatase activity and early osteogenic differentiation.

In the past decades, biomaterials were designed to induce stem cell toward osteogenic differentiation. However, conventional methods for evaluation osteogenic differentiation all required a process of cell fixation or lysis, which induce waste of a large number of cells. In this study, a fluorescence nanoprobe was synthesized by combining phosphorylated fluoresceinamine isomer I (FLA) on the surface of mesoporous silica-coated superparamagnetic iron oxide (Fe3O4@mSiO2) nanoparticles. In the presence of alkaline phosphatase (ALP), the phosphorylated FLA on the nanoprobe would be hydrolyzed, resulting in a fluorescence recovery of FLA. During early osteogenic differentiation, a high-level expression of cellular ALP was induced, which accelerated the hydrolysis of phosphorylated FLA, resulting in an enhancement of cellular fluorescence intensity. This fluorescence nanoprobe provides us a rapid and non-toxic method for the detection of cellular ALP activity and early osteogenic differentiation.

Investigation of the Compatibility and Damping Performance of Graphene Oxide Grafted Antioxidant/Nitrile-Butadiene Rubber Composite: Insights from Experiment and Molecular Simulation.

Rubber damping materials are widely used in electronics, electrical and other fields because of their unique viscoelasticity. How to prepare high-damping materials and prevent small molecule migration has attracted much attention. Antioxidant 4010NA was successfully grafted onto graphene oxide (GO) to prepare an anti-migration antioxidant (GO-4010NA). A combined molecular dynamics (MD) simulation and experimental study is presented to investigate the effects of small molecules 4010NA, GO, and GO-4010NA on the compatibility and damping properties of nitrile-butadiene rubber (NBR) composites. Differential scanning calorimetry (DSC) results showed that both 4010NA and GO-4010NA had good compatibility with the NBR matrix, and the Tg of GO-4010NA/NBR composite was improved. Dynamic mechanical analysis (DMA) data showed that the addition of GO-4010NA increased the damping performance of NBR than that of the addition of 4010NA. Molecular dynamics (MD) simulation results show GO-4010NA/NBR composites have the smallest free volume fraction (FFV) and the largest binding energy. GO-4010NA has a strong interaction with NBR due to the forming of hydrogen bonds (H-bonds). Grafting 4010NA onto GO not only inhibits the migration of 4010NA but also improves the damping property of NBR matrixes. This study provides new insights into GO grafted small molecules and the design of high-damping composites.

Synthesis of photothermal antimicrobial cotton gauze using AuNPs as photothermal transduction agents.

Cotton gauze has been used as a wound dressing since the 19th century, and still plays an important role in current clinical therapies. However, the antimicrobial ability of cotton gauze is limited. In this work, gold nanoparticles (AuNPs) were used as photothermal transduction agents to synthesize modified photothermal antimicrobial cotton gauze. The modified cotton gauze was synthesized by immersing and heating the clinical cotton gauze with AuNPs solution. XPS, ICP-OES, FTIR, XRD and SEM characterizations confirmed that AuNPs were successfully decorated on the surface of cotton gauzes. Besides, the mechanical properties, air and water vapour permeability performance of cotton gauze were not changed after modification. Photothermal antimicrobial experiments confirmed that AuNPs modified on the cotton gauze could convert light to heat, inducing rapid temperature increase of the cotton gauze. And the heat could kill microbial cells permeated in the modified cotton gauze, giving it the potential of being used for photothermal antimicrobial therapy.

PEGylated Phthalocyanine-Functionalized Graphene Oxide with Ultrahigh-Efficient Photothermal Performance for Triple-Mode Antibacterial Therapy.

This study proposes a novel multifunctional synergistic antibacterial phototherapy technique for the rapid healing of bacteria-infected wounds. By binding PEGylated phthalocyanines to the surface of graphene oxide via noncovalent functionalization, the photothermal conversion efficiency of the obtained nanocomposites can be significantly increased, which shows that the sample temperature can achieve nearly 100 °C after only 10 min of 450 nm light illumination at a concentration ≥25 µg/mL. Moreover, the nanocomposites can rapidly generate singlet oxygen under 680 nm light irradiation and physically cut bacterial cell membranes. The triple effects are expected to obtain a synergistic antibacterial efficiency and reduce the emergence of bacterial resistance. After dual-light irradiation for 10 min, the generation of hyperthermia and singlet oxygen can cause the death of Gram-positive and Gram-negative bacteria. The results of an in vivo experiment revealed that the as-prepared nanocomposites combined with dual-light-triggered antibacterial therapy can effectively restrain the inflammatory reaction and accelerate the healing of bacteria-infected wounds. These were confirmed by the examination of pathological tissue sections and inflammatory factors in rats with bacteria-infected wounds. This nanotherapeutic platform is a potential photoactivated antimicrobial strategy for the prevention and treatment of bacterial infection.

Photo-initiated enhanced antibacterial therapy using a non-covalent functionalized graphene oxide nanoplatform.

This study describes a novel antibacterial phototherapeutic platform for highly efficient healing of bacteria-infected wounds. It is based on the photodynamic and physical actions of a zinc tetraaminophthalocyanine-modified graphene oxide nanocomposite produced via non-covalent functionalization. The nanocomposite is positively charged and can easily capture negatively charged bacteria via electrostatic interactions. The antibacterial action is two-fold: (1) reactive oxygen species are produced by the phthalocyanine photosensitizer after short-term exposure to 680 nm light and (2) the graphene oxide can physically cut bacterial cell membranes. These enhanced activities can kill Gram-positive and Gram-negative bacteria at very low dosages. An ultrastructural examination indicates that this nanocomposite causes enormous damage to bacterial morphology and leakage of intracellular substances that lead to bacterial death. A rat wound model is used to demonstrate that the proposed phototherapeutic platform has low cytotoxicity and can promote rapid healing in bacteria-infected wounds. These results suggest that the integration of different antibacterial methods into a single nanotherapeutic platform is a promising strategy for anti-infective treatment.

Augmented Graphene Quantum Dot-Light Irradiation Therapy for Bacteria-Infected Wounds.

This paper proposes a highly efficient antibacterial system based on a synergistic combination of photodynamic therapy, photothermal therapy, and chemotherapy. Chitosan oligosaccharide functionalized graphene quantum dots (GQDs-COS) with short-term exposure to 450 nm visible light are used to promote rapid healing in bacteria-infected wounds. The GQDs undergo strong photochemical transformation to rapidly produce radical oxygen species and heat under light illumination, while the COS has an innate antimicrobial ability. Moreover, the positively charged GQDs-COS can easily capture bacteria via electrostatic interactions and kill Gram-positive and Gram-negative bacteria by multivalent interactions and synergistic effects. The antibacterial action of this nanocomposite causes irreversible damage to outer and inner bacterial membranes, resulting in cytoplasm leakage and death. The system has good hemocompatibility and low cytotoxicity and can improve the healing of infected wounds, as demonstrated by the examination of pathological tissue sections and inflammatory markers. These results suggest that GQDs anchored with bioactive molecules are a potential photo-activated antimicrobial strategy for anti-infective therapy.

Ag-Conjugated graphene quantum dots with blue light-enhanced singlet oxygen generation for ternary-mode highly-efficient antimicrobial therapy.

The increasing prevalence of antibiotic resistance highlights the need for new antibacterial drugs and, in particular, the development of alternative approaches such as photodynamic therapy (PDT) and photothermal therapy (PTT) to manage this growing issue. In the present study, a broad-spectrum antibacterial system was produced in which Ag nanoparticle-conjugated graphene quantum dots (GQD-AgNP) were utilised as a blue light-enhanced nanotherapeutic for efficient ternary-mode antimicrobial therapy. The successful conjugation of AgNPs onto the surface of GQDs can significantly improve the production of reactive oxygen species in light-activatable GQDs and the transformation of light energy to hyperthermia with high efficiency. There was a remarkable increase in the sample temperature of nearly 40 °C via photoexcitation after only 10 min of 450 nm laser exposure (14.2 mW cm-2). The hybrids exhibited much more efficient bactericidal capability against both Gram-negative and Gram-positive bacteria compared with GQDs alone, using 450 nm light irradiation. This is likely a consequence of their enhanced PDT, concomitant PTT, and the synergistic function of AgNPs. The antibacterial mechanism of the new-style nanocomposites was found to irreversibly destroy the bacterial membrane structure, leading to the leaking out of the cytoplasmic contents and the death of the bacteria. At low doses, the biocompatible GQD-AgNP hybrids promoted healing in bacteria-infected rat wounds, with negligible adverse impact to the normal tissue, indicating a promising future for combined photodynamic and photothermal antibacterial applications in clinical medicine.

Silkworm cocoon derived N, O-codoped hierarchical porous carbon with ultrahigh specific surface area for efficient capture of methylene blue with exceptionally high uptake: kinetics, isotherm, and thermodynamics.

Dyes are typical water contaminants that seriously affect water quality. In this study, silkworm cocoon derived N, O-codoped hierarchical porous carbon was successively developed via a facile pre-carbonization and chemical activation method, and characterized thoroughly by SEM, TEM, HRTEM, XRD, Raman, N2 adsorption and XPS. The as-prepared N, O-HPC showed a well-developed porous structure with an ultra-high specific surface area of 2270.19 m2 g-1, which proved to be a high-efficiency adsorbent. Batch adsorption experiments demonstrated that MB adsorption was highly dependent on contact time, initial MB concentration, temperature and initial solution pH. However, no remarkable effects of humic acid and ionic strength were observed. In the kinetic studies, the good applicability of a pseudo-second-order kinetic model was demonstrated. The adsorption isotherm study showed that a Langmuir isotherm model can describe the experimental data much more suitably with a maximum monolayer adsorption capacity value of 2104.29 mg g-1, which is among the highest in previously reported adsorbents and ascribed to multiple adsorption mechanisms including pore filling, π-π stacking interaction and electrostatic interaction between MB and N, O-HPC. Thermodynamic analyses suggested that MB adsorption onto N, O-HPC was spontaneous and endothermic. Furthermore, the as prepared adsorbent showed highly efficient adsorption for MB in tap water and synergistic adsorption performance toward MB and MO. Therefore, N, O-HPC derived from silkworm cocoon could be considered as an efficient, novel and advantageous material for wastewater remediation.

An injectable molecular hydrogel assembled by antimicrobial peptide PAF26 for antimicrobial application.

Wound infection is a crucial factor that inhibits wound recovery. A feasible measure to solve this problem is using antimicrobial biomaterials to suppress the microbial growth. In this work, an amphipathic antimicrobial peptide (Ac-RKKWFW-NH2, PAF26) was investigated to form the antimicrobial hydrogel. Triggered by pH, PAF26 peptide could self-assemble into a hydrogel, and the hydrogel formed was injectable and exhibited shear-thinning ability. Antimicrobial experiments demonstrated that the self-assembled hydrogel had an outstanding antimicrobial ability against pathogenic microbes such as Candida albicans, Staphylococcus aureus, and Escherichia coli via destroying the cell membrane structure. Thus, this study provides a novel method for preparing an injectable antimicrobial peptide hydrogel for antimicrobial therapies.

Immobilization adjusted clock reaction in the urea-urease-H+ reaction system.

The bell-shaped reactivity-pH curve is the fundamental reason that the temporal programmable kinetic switch in clock reactions can be obtained in bio-competitive enzymatic reactions. In this work, urease was loaded on small resin particles through ionic binding. Experimental results reveal that the immobilization not only increased the stability of the enzyme and the reproducibility of the clock reaction, but also shifted the bell-shaped activity curve to lower pHs. The latter change enables the clock reaction to occur from an initial pH of 2.3, where the free enzyme had already lost its activity. Two mechanisms explain the influence of the immobilization on the clock reaction. Immobilization modified the pH sensitive functional groups on the enzyme, shifting the activity curve to a more acidic region, and reduced diffusion alters the enzyme dynamics.

Fluorescence light-up AIE probe for monitoring cellular alkaline phosphatase activity and detecting osteogenic differentiation.

Alkaline phosphatase (ALP) is an important monophosphate hydrolase during cell mineralization and osteogenic differentiation. Though traditional methods are provided for evaluating the ALP expression in the fixed and lysed cells, at present it is still challenging to monitor the ALP activity in living cells. In this work, three phosphorylated tetraphenylethylene (TPE) probes (TPE-PA, TPE-2PA and TPE-4PA) with different numbers of -PO3H2 groups were synthesized for monitoring the ALP activity. It was found that in aqueous solution, both the TPE-PA and TPE-2PA probes were highly sensitive to ALP. In the presence of ALP, they could be quickly hydrolysed, resulting in an aggregation-induced emission (AIE) to light up ALP. While in living cells, only TPE-2PA showed good cell penetrability and high fluorescence signal-to-noise ratio during osteogenic differentiation. This probe provides us a new strategy to screen the ALP activity in living stem cells for detecting osteogenic differentiation.

Rational design of multifunctional magnetic mesoporous silica nanoparticle for tumor-targeted magnetic resonance imaging and precise therapy.

In this paper, a multifunctional theranostic magnetic mesoporous silica nanoparticle (MMSN) with magnetic core was developed for magnetic-enhanced tumor-targeted MR imaging and precise therapy. The gatekeeper ß-cyclodextrin (ß-CD) was immobilized on the surface of mesoporous silica shell via platinum(IV) prodrug linking for reduction-triggered intracellular drug release. Then Arg-Gly-Asp (RGD) peptide ligand was further introduced onto the gatekeeper ß-CD via host-guest interaction for cancer targeting purpose. After active-targeting endocytosis by cancer cells, platinum(IV) prodrug in MMSNs would be restored to active platinum(II) drug in response to the innative reducing microenvironment in cancer cells, resulting in the detachment of ß-CD gatekeeper and thus simultaneously triggering the in situ release of anticancer drug doxorubicin (DOX) entrapped in the MMSNs to kill cancer cells. It was found that with the aid of an external magnetic field, drug loaded MMSNs showed high contrast in MR imaging in vivo and exhibited magnetically enhanced accumulation in the cancer site, leading to significant inhibition of cancer growth with minimal side effects. This multifunctional MMSN will find great potential as a theranostic nanoplatform for cancer treatment.

Photo-Activatable Substrates for Site-Specific Differentiation of Stem Cells.

In this report, a UV sensitive, PEGylated PFSSTKTC (Pro-Phe-Ser-Ser-Thr-Lys-Thr-Cys) peptide was modified on quartz substrate to investigate the spatial controlled differentiation of stem cells. This substrate could restrict the cell adhesion due to the steric hindrance of PEG shell. With UV irradiation, PFSSTKTC became exposed owing to the breakage of o-nitrobenzyl group with the detachment of PEG shell. The irradiation boundary on substrate was stable in the long term. The in vitro osteogenic differentiation results revealed that under the site-specific irradiation, the mesenchymal stem cells (MSCs) could specifically differentiate into osteoblast under the induction of PFSSTKTC peptide. This photoactivatable biomaterial shows great potential for region controllable and precise MSCs differentiation.

A novel function of BMHP1 and cBMHP1 peptides to induce the osteogenic differentiation of mesenchymal stem cells.

Bone marrow homing peptide 1 (BMHP1), which was derived from a phage display peptide library (PDPL), is known to be home to bone marrow and bind to stem cells. For the first time, the effect of BMHP1 on the differentiation behavior of mesenchymal stem cells (MSCs) was evaluated. BMHP1 was tethered to modified quartz substrates, and MSCs were seeded on the substrates. It was found that BMHP1 could enhance cell adhesion and proliferation. More importantly, we found that BMHP1 could induce osteogenic differentiation either with a maintenance medium (DMEM) or osteogenic differentiation medium (ODM). Cyclic BMHP1 (cBMHP1) was further synthesized and it was found that cBMHP1 also exhibit a similar, but slightly worse effect on the osteogenic differentiation of MSCs as compared to BMHP1. This work enlightens us on the fact that BMHP1 and cBMHP1 may be used as osteogenic stimulators for MSCs based therapy.

Evaluating the effects of charged oligopeptide motifs coupled with RGD on osteogenic differentiation of mesenchymal stem cells.

Mesenchymal stem cells, due to their multilineage differentiation potential, have emerged as a promising cell candidate for cell-based therapy. In recent years, biomaterials were artificially synthesized to control the differentiation of mesenchymal stem cells. In this study, a series of charged or neutral oligopeptide motifs coupled with RGD were synthesized and used for surface modification using quartz substrates as model. Cell behaviors on the modified surfaces with different charged oligopeptide motifs were studied. It was found that these different charged oligopeptide motifs coupled with RGD were biocompatible for cell proliferation and adhesion. Moreover, it was demonstrated that the positively charged oligopeptide motif could inhibit osteogenic differentiation, while the negatively charged and neutral oligopeptide motifs could enhance osteogenic differentiation in the presence of RGD. This work may bring us enlightenment that different charged oligopeptide motifs coupled with RGD may be used for biomaterial surface modification for different stem cell-based therapies.

The synergistic effect of a BMP-7 derived peptide and cyclic RGD in regulating differentiation behaviours of mesenchymal stem cells.

Precisely controlling the behaviours of stem cells has far-reaching application potential in clinical trials. In this study, we have developed a self-assembled monolayer (SAM) of a cyclic RGD peptide (cycRGD) and bone forming peptide-1 (BFP-1) on a quartz substrate to regulate the behaviours of mesenchymal stem cells (MSCs). The results demonstrated that cycRGD can accelerate the cell adhesion on the substrate, thereby enhancing the ability of BFP-1 in mediating the osteogenic activity. And the synergistic effect between these two functional peptides in osteogenic differentiation of MSCs was confirmed in terms of immunofluorescent staining, Alizarin Red S staining for mineralization and alkaline phosphatase (ALP) activity assay. This finding might give a new insight into designing functional substrates to regulate desired differentiation of stem cells.