Tannic acid-mediated synthesis of flower-like mesoporous MnO2 nanostructures as T1-T2 dual-modal MRI contrast agents and dual-enzyme mimetic agents.

This study introduces a simple method for preparing a new generation of MnO2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO2 NMs, flower-like M1-MnO2 and near-spherical M2-MnO2, were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (Ms), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO2. Furthermore, the signal intensity and r1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T1 MRI contrast activities could be employed as a promising theranostic system for future purposes.

A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies.

A novel theranostic nanoplatform was prepared based on Fe3O4 nanoparticles (NPs) coated with gadolinium ions decorated-polycyclodextrin (PCD) layer (Fe3O4@PCD-Gd) and employed for Curcumin (CUR) loading. The dissolution profile of CUR indicated a pH sensitive release manner. Fe3O4@PCD-Gd NPs exhibited no significant toxicity against both normal and cancerous cell lines (MCF 10A and 4T1, respectively); while the CUR-free NPs showed more toxicity against 4T1 than MCF 10A cells. In vivo anticancer study revealed appropriate capability of the system in tumor shrinking with no tissue toxicity and adverse effect on body weight. In vivo MR imaging of BALB/c mouse showed both T1 and T2 contrast enhancement on the tumor cells. Fe3O4@PCD-Gd/CUR NPs showed significant features as a promising multifunctional system having appropriate T1-T2 dual contrast enhancement and therapeutic efficacy in cancer theranostics.

Optimization of immobilization conditions of Bacillus atrophaeus FSHM2 lipase on maleic copolymer coated amine-modified graphene oxide nanosheets and its application for valeric acid esterification.

The thermoalkalophilic lipase from Bacillus atrophaeus (BaL) was immobilized onto amine-functionalized graphene oxide nanosheets coated with the poly (maleic anhydride-alt-1-octadecene) copolymer (GO-NH2-PMAO) and activated with glutaraldehyde as spacer arm through interfacial activation and subsequent multipoint covalent attachment. Experimental design method was applied for optimization of immobilization conditions including GO-NH2-PMAO concentration, buffer concentration, pH, sonication time, enzyme concentration, glutaraldehyde concentration, time, and temperature. The optimum specific activity of the immobilized BaL (105.95 ± 2.37 U/mg) reached at 5 mg/mL for GO-NH2-PMAO, 25 mM of buffer, pH 6.0, 60 min sonication time, 100 mM glutaraldehyde, 60 U/mL of enzyme, and 4 h of immobilization time at 25 °C, which was very close to the predicted amount (106.08 ± 1.42 U/mg). Maximum immobilization yield (81.35%) and efficiency (277.63%) were determined in optimal immobilization conditions. The obtained results clearly indicated that the immobilized BaL exhibited better stability at extreme temperature and pH than the free BaL. At temperature of 90 °C and pH 11, more than 90% of the initial activity of the immobilized BaL was retained. Furthermore, the immobilized BaL retained about 90% of its initial activity after 10 days of storage and 6 cycles of application. The esterification studies showed that maximum bioconversion of valeric acid to pentyl valerate using the free BaL (34.5%) and the immobilized BaL (96.3%) occurred in the xylene medium after 48 h of incubation at 60 °C. Therefore, the BaL immobilized on GO-NH2-PMAO was introduced as an effective biocatalyst to synthesize green apple flavour ester.

In vitro and in vivo characteristics of doxorubicin-loaded cyclodextrine-based polyester modified gadolinium oxide nanoparticles: a versatile targeted theranostic system for tumour chemotherapy and molecular resonance imaging.

ß-Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic system (Gd2O3@PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd2O3@PCD-FA was fully characterised by FTIR, vibrating sample magnetometer, TGA, XRD, SEM and TEM analyses. The dissolution profile of DOX showed a pH sensitive release. No significant toxicity was observed for the targeted NPs (Gd2O3@PCD-FA) and DOX-loaded NPs inhibiting M109 cells viability more efficiently than free DOX. Moreover, the negligible hemolytic activity of the targeted NPs showed their appropriate hemocompatibility. The preferential uptake was observed for the developed Gd2O3@PCD-FA-DOX NPs in comparison with Dotarem using T1- and T2-weighted MRI in the presence of folate receptor-positive and folate receptor-negative cancer cells (M109 and 4T1, respectively). Furthermore, in vivo studies revealed that Gd2O3@PCD-FA-DOX not only exhibited considerably relaxivity performance as a contrast agent for MRI, but also improved in vivo anti-tumour efficacy of the system. The results suggest that Gd2O3@PCD-FA-DOX improves its therapeutic efficacy in the treatment of solid tumours and also reduces the adverse effects, so it could be proposed as a promising drug delivery system for chemotherapy and molecular imaging diagnosis in MRI.

Folic acid decorated magnetic nanosponge: An efficient nanosystem for targeted curcumin delivery and magnetic resonance imaging.

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (Fe3O4/CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (Fe3O4/CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (Fe3O4/CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free Fe3O4/CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded Fe3O4/CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). Fe3O4/CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T2 MR signal intensity for Fe3O4/CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the Fe3O4/CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T2 MRI contrast efficiency.

Improved curcumin loading, release, solubility and toxicity by tuning the molar ratio of cross-linker to ß-cyclodextrin.

A novel ß-cyclodextrin-based nanosponge (CDNS) was proposed as curcumin (CUR) delivery system improving pharmacokinetics and anticancer activity of CUR. The effect of molar ratio of Epiclon (EPI) as cross-linker and ß-cyclodextrin (ßCD) on the porosity, surface area, swelling ratio, CUR solubility and loading capacity, rate of drug release and selective toxicity of the CDNSs was fully investigated. The high degree of cross-linking led to the formation of mesoporous CDNS having high specific surface area and high loading capacity. All CUR-free CDNSs showed no toxicity against MCF 10A and 4T1 cells as normal and cancerous cells, respectively. While CDNSs-CUR exhibited selective toxicity against cancerous cells. In sum, high CUR aqueous solubility, significant loading and controllable release of the CUR, outstanding and selective toxicity against cancerous cells make CDNS8-CUR (EPI/ßCD = 8) as promising candidate for further study in the cancer therapy.

Gadolinium (III) oxide nanoparticles coated with folic acid-functionalized poly(ß-cyclodextrin-co-pentetic acid) as a biocompatible targeted nano-contrast agent for cancer diagnostic: in vitro and in vivo studies.

OBJECTIVES: In this study, a novel targeted MRI contrast agent was developed by coating gadolinium oxide nanoparticles (Gd2O3 NPs) with ß-cyclodextrin (CD)-based polyester and targeted by folic acid (FA). MATERIALS AND METHODS: The developed Gd2O3@PCD-FA MRI contrast agent was characterized and evaluated in relaxivity, in vitro cell targeting, cell toxicity, blood compatibility and in vivo tumor MR contrast enhancement. RESULTS: In vitro cytotoxicity and hemolysis assays revealed that Gd2O3@PCD-FA NPs have no significant cytotoxicity after 24 and 48 h against normal human breast cell line (MCF-10A) at concentration of up to 50 µg Gd+3/mL and have high blood compatibility at concentration of up to 500 µg Gd+3/mL. In vitro MR imaging experiments showed that Gd2O3@PCD-FA NPs enable targeted contrast T1- and T2-weighted MR imaging of M109 as overexpressing folate receptor cells. Besides, the in vivo analysis indicated that the maximum contrast-to-noise ratio (CNR) of tumor in mice increased after injection of Gd2O3@PCD-FA up to 5.89 ± 1.3 within 1 h under T1-weighted imaging mode and reduced to 1.45 ± 0.44 after 12 h. While CNR increased up to maximum value of 1.98 ± 0.28 after injection of Gd2O3@PCD within 6 h and reduced to 1.12 ± 0.13 within 12 h. CONCLUSION: The results indicate the potential of Gd2O3@PCD-FA to serve as a novel targeted nano-contrast agent in MRI.

Endotoxin removal from aqueous solutions with dimethylamine-functionalized graphene oxide: Modeling study and optimization of adsorption parameters.

Novel graphene oxide (GO)-based adsorbent embedded with epichlorohydrin (ECH) as a coupling agent and dimethylamine (DMA) as a ligand (GO-ECH-DMA) were prepared and employed for endotoxin removal from aqueous solutions. The physicochemical properties of nanocomposite were fully characterized. The model attributed to batch adsorption process was optimized employing response surface methodology (RSM) via various parameters such as pH, GO-ECH-DMA dosage, and contact time and endotoxin concentration. The p-value with low probability (<0.00001), determination coefficient (R2=0.99) and the non-significant lack of fit (p > 0.05) showed a quadratic model with a good fit with experimental terms. The synergistic effects of the linear term of contact time and GO-ECH-DMA dosage on endotoxin removal were significant. The optimum condition for endotoxin removal was obtained at pH of 5.52, GO-ECH-DMA dosage of 21 mgL-1, contact time of 56 min and endotoxin concentration of 51.3 endotoxin units per milliliter (EUmL-1). The equilibrium was the better explained by Langmuir isotherm with the maximum monolayer adsorption capacity of 121.47 EUmg-1, while the kinetics of the endotoxin adsorption process was followed by the pseudo-second-order model. The adsorbent could be recycled with NaOH. The possible mechanisms of endotoxin adsorption were proposed by hydrogen-bonding, π-π stacking, and electrostatic interaction.

Theranostic α-Lactalbumin-Polymer-Based Nanocomposite as a Drug Delivery Carrier for Cancer Therapy.

A nanotheranostic system was developed using α-lactalbumin along with Fe3O4 nanoparticles as an magnetic resonance imaging (MRI) contrast agent for medical imaging and doxorubicin as the therapeutic agent. α-lactalbumin was precipitated and cross-linked using poly(ethylene glycol) and glutaraldehyde. Besides, polyethylenimine was applied to increase the number of amine groups during cross-linking between α-lactalbumin and Fe3O4 nanoparticles. Interestingly, 90% of the initial protein used for the coaggregation process was incorporated in the prepared 130 nm nanocomposites, which facilitated the 85% doxorubicin loading. Formation of pH-sensitive imine bonds between glutaraldehyde and amine groups on α-lactalbumin and polyethylenimine resulted in higher release of doxorubicin at acidic pHs and consequently development of a pH-sensitive nanocarrier. The designed nanocomposite was less immunogenic owing to stimulating the production of less amounts of C3a, C5a, platelet factor 4, glycoprotein IIb/IIIa, platelet-derived ß-thromboglobulin, interleukin-6, and interleukin-1ß compared to the free doxorubicin. Furthermore, 1000 µg/mL nanocomposite led to 0.2% hemolytic activity, much less than the 5% standard limit. The void nanocarrier induced no significant level of cytotoxicity in breast cancer and normal cells following 96 h incubation. The doxorubicin-loaded nanocomposite presented higher cytotoxicity, apoptosis induction, and doxorubicin uptake in cancer cells than free doxorubicin. Conversely, lower cytotoxicity, apoptosis induction, and doxorubicin uptake were observed in normal cells treated with the doxorubicin-loaded nanocarrier compared to free doxorubicin. In line with the results of in vitro experiments, in vivo studies on tumor-bearing mice showed more suppression of tumor growth by the doxorubicin-loaded nanocomposite compared to the free drug. Moreover, the pharmacokinetic study revealed slow release of doxorubicin from the nanocomposite. Besides, in vitro and in vivo MRI studies presented a higher r2/r1 ratio and comparable contrast to the commercially available DOTAREM, respectively. Our findings suggest that this new nanocomposite is a promising nanotheranostic system with promising potential for cancer therapy and diagnosis.

Carnosine-graphene oxide conjugates decorated with hydroxyapatite as promising nanocarrier for ICG loading with enhanced antibacterial effects in photodynamic therapy against Streptococcus mutans.

Antimicrobial photodynamic therapy (aPDT) has been emerged as a noninvasive strategy to remove bacterial contaminants such as S. mutans from the tooth surface. Photosensitizer (PS), like indocyanine green (ICG), plays a key role in this technique which mainly suffers from the poor stability and concentration-dependent aggregation. An appropriate nanocarrier (NC) with enhanced antibacterial effects could overcome these limitations and improve the efficiency of ICG as a PS. In this study, various ICG-loaded NCs including graphene oxide (GO), GO-carnosine (Car) and GO-Car/Hydroxyapatite (HAp) were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Filed Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive Spectroscopy (EDS), Zeta Potential and Ultraviolet-Visible spectrometry (UV-Vis). The colony forming unit and crystal violet assays were performed to evaluate the antimicrobial and anti-biofilm properties of PSs against S. mutans. The quantitative real-time PCR approach was also applied to determine the expression ratio of the gtfB gene in S. mutans. The zeta potential analysis and UV-Vis spectrometry indicated successful loading of ICG onto/into NCs. GO-Car/HAp showed highest amount of ICG loading (57.52%) and also highest aqueous stability after one week (94%). UV-Vis spectrometry analyses disclosed a red shift from 780 to 800 nm for the characteristic peak of ICG-loaded NCs. In the lack of aPDT, GO-Car@ICG showed the highest decrease in bacterial survival (86.4%) which indicated that Car could significantly promote the antibacterial effect of GO. GO@ICG, GO-Car@ICG and GO-Car/HAp@ICG mediated aPDT, dramatically declined the count of S. mutans strains to 91.2%, 95.5% and 93.2%, respectively (P < 0.05). The GO@ICG, GO-Car@ICG, GO-Car/HAp@ICG significantly suppressed the S. mutans biofilm formation by 51.4%, 63.8%, and 56.8%, respectively (P < 0.05). The expression of gtfB gene was considerably reduced to 6.0, 9.0 and 7.9-fold after aPDT in the presence of GO@ICG, GO-Car@ICG, GO-Car/HAp@ICG, respectively (P < 0.05). It could be concluded that the multi-functionalized GO as a novel nanocarrier could significantly enhance the ICG loading, stability, and improve its inhibitory effects as a photosensitizer in aPDT against S. mutans. These findings might provide opportunity for efficient treatment of local dental infections.

Selective removal of lead ions from aqueous solutions using 1,8-dihydroxyanthraquinone (DHAQ) functionalized graphene oxide; isotherm, kinetic and thermodynamic studies.

An anthraquinone - graphene structure was fabricated and applied for the removal of lead(ii) from aqueous solution. The equilibrium occurred in about 10 min revealing the high adsorption rate at the beginning of the process. The maximum Pb(ii) adsorption capacity of the Fe3O4@DHAQ_GO nanocomposite was about 283.5 mg g-1 that was observed at 323 K and pH 5.5. The Pb(ii) adsorption ability increased with the increasing pH. The isotherm and kinetic studies indicated that the Sips isotherm model and the linear form of the pseudo-second kinetic model had a better fit with the experimental results. The positive value of ΔH 0 indicated endothermic interactions between Pb(ii) and Fe3O4@DHAQ_GO. The negative ΔG 0 indicated that the reactions are spontaneous with a high affinity for Pb(ii). The positive ΔS 0 values indicated increasing randomness at the solid-solute interface during the adsorption process. The selective removal of Pb(ii) by the nanocomposite confirms the presence of higher-affinity binding sites for Pb(ii) than Cd(ii), Co(ii), Zn(ii), and Ni(ii) ions. Furthermore, the Fe3O4@DHAQ_GO nanocomposite revealed an excellent preferential adsorbent for Pb(ii) spiked in drinking water samples containing natural ion matrices. EDTA-2NA 0.01 N was found to be a better elution agent than HCl 0.1 M for the nanocomposite regeneration. After five adsorption/desorption cycles using EDTA-2NA 0.01 N, more than 84% of the adsorbed Pb(ii) was still desorbed in 30 min. Capturing sub-ppm initial concentrations of Pb(ii) and the capability to selectively remove lead from drinking water samples make the Fe3O4@DHAQ_GO nanocomposite practically convenient for water treatment purposes. High adsorption capacity and facile chemical synthesis route are the other advancements.

The effect of indocyanine green loaded on a novel nano-graphene oxide for high performance of photodynamic therapy against Enterococcus faecalis.

BACKGROUND: Recently developed photodynamic therapy (PDT) has gained attention for achieving effective root canal disinfection. Using an optimized nontoxic photosensitizer (PS), such as indocyanine green (ICG), is an imperative part of this technique. Therefore, the objective of the current study was to improve ICG photodynamic properties through incorporation of ICG into nano-graphene oxide (NGO) in order to produce NGO-ICG as a new PS and also to assess the antimicrobial effects of NGO-ICG against Enterococcus faecalis after photodynamic therapy. MATERIALS AND METHODS: NGO-ICG was synthesized based on oxidation of graphite flakes and direct loading of ICG onto NGO. NGO-ICG formation was confirmed using the Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), and UV-vis spectrometry. The antimicrobial and anti-biofilm potential of NGO-ICG-PDT against E. faecalis was assessed via colony forming unit and crystal violet assays, respectively. RESULTS: FT-IR, SEM and UV-vis spectrometry confirmed successful synthesis of NGO-ICG containing 200µg/mL of ICG. NGO-ICG-PDT at an energy density of 31.2J/cm2 showed a significant reduction (2.81 log) in the count of E. faecalis (P<0.05). NGO-ICG-PDT significantly reduced the biofilm formation ability of E. faecalis up to 99.4% (P<0.05). The overall antimicrobial and anti-biofilm potential of NGO-ICG-PDT was higher than PDT based on ICG (1000µg/mL) (47% and 21%, respectively). CONCLUSION: Because NGO-ICG-PDT showed a significant reduction in the number and biofilm formation ability of E. faecalis at low ICG concentrations (200µg/mL), it could be a new approach to adjuvant treatment of endodontic infections.

Comparison of Moringa stenopetala seed extract as a clean coagulant with Alum and Moringa stenopetala-Alum hybrid coagulant to remove direct dye from Textile Wastewater.

In this study, the efficiency of Moringa stenopetala seed extract was compared with alum and M. stenopetala-alum hybrid coagulant to remove Direct Red 23 azo dye from textile wastewater. The effects of parameters such as pH, coagulant dose, type of salt used for the extraction of coagulant and initial dye concentration on dye removal efficiency were investigated. Moreover, the existing functional groups on the structure of M. stenopetala coagulant (MSC) were determined by Fourier transform infrared spectroscopy, and the morphology of sludge produced by MSC, alum, and hybrid coagulant was characterized by scanning electron microscopy. Ninhydrin test was also used to determine the quantity of primary amines in the MSC and Moringa oleifera coagulant (MOC). According to the results, with increasing the coagulant dose and decreasing the initial dye concentration, dye removal efficiency has increased. The maximum dye removal of 98.5, 98.2, and 98.3 % were obtained by using 240, 120, and 80 mg/L MSC, alum and hybrid coagulant at pH 7, respectively. The results also showed MSC was much more effective than MOC for dye removal. The volume of sludge produced by MSC was one fourth and half of those produced by alum and hybrid coagulant, respectively. Based on the results, hybrid coagulant was the most efficient coagulant for direct dye removal from colored wastewater.

Response surface modeling of lead (׀׀) removal by graphene oxide-Fe3O4 nanocomposite using central composite design.

BACKGROUND: Magnetic graphene oxide (Fe3O4@SiO2-GO) nanocomposite was fabricated through a facile process and its application as an excellent adsorbent for lead (II) removal was also demonstrated by applying response surface methodology (RSM). METHODS: Fe3O4@SiO2-GO nanocomposite was synthesized and characterized properly. The effects of four independent variables, initial pH of solution (3.5-8.5), nanocomposite dosage (1-60 mg L(-1)), contact time (2-30 min), and initial lead (II) ion concentration (0.5-5 mg L(-1)) on the lead (II) removal efficiency were investigated and the process was optimized using RSM. Using central composite design (CCD), 44 experiments were carried out and the process response was modeled using a quadratic equation as function of the variables. RESULTS: The optimum values of the variables were found to be 6.9, 30.5 mg L(-1), 16 min, and 2.49 mg L(-1) for pH, adsorbent dosage, contact time, and lead (II) initial concentration, respectively. The amount of adsorbed lead (II) after 16 min was recorded as high as 505.81 mg g(-1) for 90 mg L(-1) initial lead (II) ion concentration. The Sips isotherm was found to provide a good fit with the adsorption data (KS = 256 L mg(-1), nS = 0.57, qm = 598.4 mg g(-1), and R(2) = 0.984). The mean free energy Eads was 9.901 kJ/mol which confirmed the chemisorption mechanism. The kinetic study determined an appropriate compliance of experimental data with the double exponential kinetic model (R(2) = 0.982). CONCLUSIONS: Quadratic and reduced models were examined to correlate the variables with the removal efficiency of Fe3O4@SiO2-GO. According to the analysis of variance, the most influential factors were identified as pH and contact time. At the optimum condition, the adsorption yield was achieved up to nearly 100 %.