Constructing green superhydrophilic and superoleophobic COFs-MOFs hybrid-based membrane for efficiently emulsion separation and synchronous removal of microplastics, dyes, and pesticides.

Oil spills and micropollutants have become thorny environmental issues, posing serious threat to ecosystem and human health. To settle such dilemma, this study successfully constructed a robust and environmentally-friendly MOFs-COFs hybrid-based membrane (FS-50/COF(MATPA)-MOF(Zr)/PDA@PVDF) for the first time through solution synthesis and solvothermal method, combined with surface modification of FS-50 molecule. Importantly, we employed a simple two-step strategy to obtain the high-aspect-ratio MOFs fibers: (1) solvent regulation to generate smaller needle-like whiskers during the in-situ growth of MOFs on COFs; (2) high pressure induced directional crystallization in filtration process. The introduction of polydopamine (PDA) greatly improved the adhesion between coating and PVDF membrane. The in-situ growth of high length-diameter ratio MOFs fibers on blocky COFs greatly enhanced the specific surface area of MOFs-COFs hybrid, thus provided sufficient absorption sites. The functional groups of FS-50 endowed the hybrid membrane with superhydrophilicity and superoleophobicity, which facilitated to selectively penetrate water molecules and repel non-polar pollutants. The separation efficiency and decontamination mechanism of hybrid membrane to the simulated oily wastewater (containing various MPs, dyes, and pesticides) were investigated through experiments and theoretical calculations. The hybrid membrane could selectively and synchronously adsorb various dyes (20 mg/L-120 mg/L, almost 100% removal) and pesticides (10 mg/L for DIF and TET, adsorption rates 93.2% and 90.9%, respectively) from oil-water emulsion (50 mL). The large-scale coated sponge (6 cm × 4.5 cm × 3 cm) could quickly achieve separation of oil-water mixture (almost 100%) with a water permeability of more than 162 L m-2·h-1·bar-1, and simultaneously remove various MPs (PP-2000, PP-100, PE-2000, PS-100, 0.2 g/300 mL for each), Sudan Ⅲ (C0 = 200 mg/L), and DIF (C0 = 10 mg/L) from a simulant oily wastewater (300 mL), with the removal rates of almost 100% for MPs, 99.7% for Sudan Ⅲ, and 95.8% for DIF. Furthermore, we elucidated the removal mechanism of pesticide and dyes through simulating the theoretical adsorption energy and potential adsorption sites. The hybrid membrane not only provides a promising candidate for the removal of multiple pollutants from oil-water emulsion, but also opens a new strategy for achieving efficient and clean aquatic environment restoration.

Inhibition of gingival fibroblast necroptosis mediated by RIPK3/MLKL attenuates periodontitis.

AIM: Necroptosis participates in the pathogenesis of many inflammatory diseases, including periodontitis. Here, we aimed to investigate the role and mechanism of necroptosis inhibitors in attenuating periodontitis. MATERIALS AND METHODS: The Gene Expression Omnibus (GEO) dataset GSE164241 was re-analysed to identify the role of necroptosis in periodontitis. Gingival specimens from healthy subjects or periodontitis patients were collected to evaluate the expression level of necroptosis-associated proteins. The therapeutic effect of necroptosis inhibitors on periodontitis was assessed in vivo and in vitro. Moreover, Transwell assays and Western blotting and siRNA transfection were used to identify the effects of necroptotic human gingival fibroblasts (hGFs) on THP-1 macrophages. RESULTS: Re-analysis revealed that gingival fibroblasts (GFs) in periodontitis gingiva showed the highest area under the curve score of necroptosis. Elevated levels of necroptosis-associated proteins were identified in GFs in periodontitis gingiva collected from patients and mice. In ligature-induced periodontitis mice, local administration of receptor interacting protein kinase 3(RIPK3) inhibitor GSK'872 or sh-mixed-lineage kinase domain-like pseudokinase (Mlkl) markedly abrogated necroptosis and rescued periodontitis. Analogously, necroptosis inhibitors alleviated the inflammatory response and release of damage-associated molecular patterns in lipopolysaccharide- or LAZ (LPS + AZD'5582 + z-VAD-fmk, necroptosis inducer)-induced GFs and then reduced THP-1 cell migration and M1 polarization. CONCLUSIONS: Necroptosis in GFs aggravated gingival inflammation and alveolar bone loss. Necroptosis inhibitors attenuate this process by modulating THP-1 macrophage migration and polarization. This study offers novel insights into the pathogenesis and potential therapeutic targets of periodontitis.

Tumor-Targeting Anti-MicroRNA-155 Delivery Based on Biodegradable Poly(ester amine) and Hyaluronic Acid Shielding for Lung Cancer Therapy.

Anti-microRNA-155 (anti-miR-155), an oligonucleotide with a complimentary sequence to microRNA-155, holds great promise for lung cancer therapy, and thus some cationic materials have been used to deliver anti-miR-155 into lung tumors. Although the gene delivery capacity in vitro was favorable, the application in vivo was limited by rapid removal and significant cytotoxicity, which were mainly caused by the positive charge of the gene complexes. Therefore, it was necessary to develop a novel carrier to decrease the positive charge and increase the gene delivery capacity into the tumor site. In this paper, biodegradable poly(ester amine) (PEA) was used to condense anti-miR-155 into PEA/anti-miR-155 complexes, and natural anionic polysaccharide hyaluronic acid (HA) was modified with a lung tumor cell targeting peptide and then coated on the surface of gene complexes. The formed hyaluronic acid shielding, PEA/anti-miR-155/HA-peptide complexes were monodispersed, and the particle size and zeta potential were 362.7 nm and -10.17 mV, respectively. In addition, the PEA/anti-miR-155/HA-peptide complexes had good biocompatibility and stability in vitro, and the lung tumor growth inhibitions of PEA/anti-miR-155/HA-peptide in vitro and in vivo were also excellent. The PEA/anti-miR-155/HA-peptide complexes play an active role in tumor growth inhibition and could be useful for lung cancer therapy.

Synthesis, characterization, and application of amino-terminated poly(ethylene glycol)-block-poly(epsilon-caprolactone) copolymer for paclitaxel.

In this paper, we successfully synthesized amino-terminated poly(ethylene glycol)-block-poly (epsilon-caprolactone) (NH2-PEG-PCL) block copolymer from polyethylene glycol 2000, epsilon-caprolactone (epsilon-CL) and hydrazine hydrate. The obtained copolymer was characterized by nuclear magnetic resonance (1H-NMR), the molecular weight and distribution of NH2-PEG-PCL were characterized by Gel permeation chromatography (GPC). The NH2-PEG-PCL copolymer could self-assemble into micelles in water. Paclitaxel (PTX) loaded NH2-PEG-PCL (PNPP) micelles were prepared by solid dispersion technique without organic solvent. The micelles were characterized by XRD, TEM and Malvern laser particle size. The results of this work indicated that PNPP micelles were uniform and spherical shapes in solution. The average size and zeta potential of PNPP (DL = 8%) in water was about 97.1 +/- 1.2 nm, +13.9 +/- 0.6 mV, respectively. The in vitrodrug release profile of PNPP micelles showed a clear slow-release effect. The results suggested that NH2-PEG-PCL copolymer might be an excellent carrier for hydrophobic drugs such as PTX. In particular, the NH2-PEG-PCL polymer has potential value for modifying with ligands to work as active targeting drug delivery carriers, which has great significance for cancer therapeutics.

Sorption and desorption of bisphenols on commercial plastics and the effect of UV aging.

Plastics gradually degrade in the natural environment from the effect of irradiation, which can change the surface properties of plastics and affect the migration behaviour of pollutants. Up to now, studies on the sorption/desorption behaviour of organic pollutants on aged plastics are still limited. In this study, several types of commercial plastics (polyurethane (PU), polyamide (PA), polyvinyl chloride (PVC), expanded polystyrene (EPS)) were selected to investigate the sorption and release behaviour for four kinds of bisphenols (bisphenol-F, A, B, AP). The results from Raman spectroscopy and scanning electron microscopy (SEM) analysis showed evidence of oxidization and surface cracks of plastics after irradiation. The sorption behaviour for both fresh and aged plastics were dominated by hydrophobicity. In addition, the electrostatic force, H-bonding interaction, and π-π interaction were also the important factors impacting the sorption process. The desorption kinetics behaviour indicates that desorption becomes faster after aging. Hydrophobicity is also an important factor that affects desorption behaviour. This study showed that sorption capacity for most fresh and aged plastics was enhanced by the impact of salinity and dissolved organic matter (DOM). Increased temperature could increase the desorption of bisphenols on both fresh and aged plastics, which illustrated that warm environments would promote more pollutants be released from plastics to water bodies.

Engineering green MOF-based superhydrophobic sponge for efficiently synchronous removal of microplastics and pesticides from high-salinity water.

Microplastics (MPs) and pesticides are becoming an intractable environmental issue due to their wide spreading and non-degradable nature, posing serious threat to ecosystem and human health. To settle such dilemma, this work reasonably designed a superhydrophobic MOF-based coated sponge (ODSOSS/TiO2/Ni-MOF/PDA@Sponge) through the combination of an environmentally friendly in-situ supersaturated coprecipitation and polysesiloxane modification method. Among them, (I) the introduction of polydopamine (PDA) not only improves the adhesion between coatings and sponge, but also enhances the growth of MOF structure through complexation. (II) The obtained Ni-MOF shows large-area microscale anthemy structure with multilayered flaky texture, forming heterogeneously hierarchical structure with the deposited TiO2 nanoparticles, which promotes photodegradation ability of TiO2 owing to great specific surface area of Ni-MOF. (III) The high specific large area Ni-MOF supplies sufficient action sites for linkage of PDA and polysesiloxane molecules with unique nanocage-like structure, thus further greatly increasing adsorption force for various pollutants. (IV) The superhydrophobicity protect the porous channels of MOF from contamination of various absorbed pollutants, while TiO2 nanoparticles effectively photodegrade the absorbed organic pollutants, endowing the sponge superior recyclability. The superhydrophobic sponge selectively rapidly and synchronously adsorbs various MPs (maintained almost 100% after 60 cycles) and pesticides (adsorption rates 71.6%-95.1%) from high-salinity water. The large-area sponge (9 cm × 6 cm × 1 cm) simultaneously removes almost 100% MPs (40 mg/L), Sudan Ⅲ (10 mg/L), kerosene (30 mL/L), and four pesticides (10 mg/L) within 1 min. Particularly, four pesticides are quickly photocatalytic degraded by the coated sponge. The free radical capture trials show that hydroxyl radicals (·OH) are the main active species of pesticide degradation. Furthermore, we reveal the negative centers where pesticide molecules are most vulnerable to ·OH attack, on basis of the charge distribution and molecular electrostatic potential (MEP) analysis. The adsorption mechanisms are carefully clarified through theoretical calculation and experimental data. This work not only provide an effective superhydrophobic candidate for MPs and pesticides removal in a broad applicable scope (especially in high-salinity wastewater), but also opens a new strategy for environmental remediation.

Mechanically durable anti-bacteria non-fluorinated superhydrophobic sponge for highly efficient and fast microplastic and oil removal.

Microplastics (MPs) pollution evolves into a global environmental problem to be solved urgently. Although many studies are exploring ways to remove MPs from water environment, most of them are lack of selectivity and low efficiency. Herein, considering the fascinating absorption selectivity of superwetting materials, a robust magnetic-responsive superhydrophobic and superoleophilic sponge was firstly used to quickly eliminate MPs from water with very high efficiency. The functional sponge was fabricated by a non-fluorinated coating technique that consisted of polydimethylsiloxane (PDMS) grafted Fe3O4 particle, PDMS grafted halloysite nanotubes, and PDMS binder. The coated sponge achieved excellent mechanically durable and chemically stable superhydrophobicity that resisted a series of severe treatments. It was unquestionable to show very fast oil absorption. What's more, it especially showed very high adsorption capacity (24.3-48.2 mg/g) and could quickly adsorb almost 100% MPs (polypropylene, polyvinyl chloride, and polyethylene) from aqueous suspensions. Moreover, the removal rates remained almost 100% for these MPs after 50 cycles. Besides, the coated sponge had excellent salt tolerance and antibacterial activity to Escherichia coli (E. coli) (99.91%) and Staphylococcus aureus (S. aureus) (90.46%). The adsorption mechanism of the coating was discussed from the perspectives of molecular structure, electronic effect, steric hindrance, and size-scale effect. The absorption driving force mainly derived from the intra-particle diffusion under capillary attraction, whilst slight electrostatic interaction, hydrogen bond interaction, and σ-p (or p-p) conjugation between PDMS and MPs. This functional sponge was destined to be a new strategy in the removal of MPs and other solid pollutants, especially in the high-salinity and rich-microorganism water environment.

Preparation of acrylamide and carboxymethyl cellulose graft copolymers and the effect of molecular weight on the flocculation properties in simulated dyeing wastewater under different pH conditions.

In this study, graft copolymers with different graft ratios (GRs) and molecular weights (MWs) were prepared by water bath polymerization using acrylamide (AM) and carboxymethyl cellulose (CMC) as substrates; additionally, the best preparation parameters were provided. The MW of the copolymer was inversely correlated with the GR (R = -0.82). The obtained graft copolymer was characterized by FTIR, 1H NMR, XPS and DSC. The results showed that CMC and AM were successfully copolymerized and the thermal stability of the product is improved. The graft copolymers with different MWs were used to flocculate a simulated dyeing wastewater at pH values of 3, 5, 7, 9 and 11. The results showed that as the molecular weight of the graft copolymers increased, the average flocculation settling ratio decreased drastically from 61.2% to 19.4% at pH 3, and the higher the MW, the better the flocculation settling performance. But the average settling ratio increased sharply at pH 11, and the increase grew from 21.0% to 50.3%. The larger the MW, the more obvious the decrease in flocculation sedimentation performance. The supernatant turbidity was reduced from 13324 NTU to less than 150 NTU, and the turbidity removal ratio exceeded 99%. The flocculation mechanism was discussed.

α-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence imaging guided photothermal therapy/chemotherapy of breast cancer.

Micellar nanoparticles have unique advantages as carriers for therapeutic or imaging agents, owing to their smaller size and better penetration of tumors. However, some agents, due to their physical or chemical properties, are difficult to load into micelles. IR780 is one of these agents, and is also a promising near-infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer photothermal therapy (PTT). Its hydrophobic and high crystallization structure results in limited bioavailability in vivo. It is difficult to load into micelles constructed from an amphiphilic block polymer with relatively low molecular weight. In this study, we use computer simulation and introduce another small biomolecule, α-lipoic acid, into the micelles constructed from a mPEG-PCL copolymer, to lower the energy of molecular interaction between MPEG-PCL and IR780, and expect to enhance the loading capacity of the micelles to IR780. The introduction of α-lipoic acid decreases the energy of molecular interaction between MEPG-PCL and IR780 from -46.18 kJ mol-1 to -196.52 kJ mol-1 and increases the loading capacity and stability of the mPEG-PCL micelles to IR780, which also maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

Biodegradable Interlayer-Crosslinked Polymer Micelles with Reduction Sensitivity for Non-Small Cell Lung Cancer Therapy.

To achieve higher therapeutic efficiency with catabatic side effects, desirable nanocarriers should be designed to retain the loaded drug tightly during the systemic circulation, but release the drug rapidly and efficiently upon endocytosis by tumor cells. Herein, we synthesized a novel folate conjugated poly(ethylene glycol)-poly(L-glutamic acid)-poly(L-phenylalanine) (folate-PEG-PLG(HS)-PPhe) copolymer to achieve a desired controlled delivery of doxorubicin (DOX). The copolymer could self-assemble into interlayer-crosslinked micelles with reduction sensitivity, and DOX was successfully loaded into the interior of copolymer. The interlayer-crosslinked disulfide bond at the intermediate region of between PEG and poly(L-phenylalanine) led to significant improvement of the system stability through the introduction of an additional mechanism of carrier/carrier interaction. The crosslinked interlayer could be cleaved at the desired target site under tumor-relevant reductive conditions and DOX were rapidly released from the DOX loaded folate-PEG-PLG (HS)-PPhe micelles (DOX-fPGPM), and significantly lowered the drug leakage without glutathione (GSH). Importantly, the DOX-fPGPM exhibited significantly higher antitumor efficiency both in vitro and in vivo in comparison with free DOX, and Doxil (commercial doxorubicin-loaded liposomes). Biodistribution studies showed that DOX more effectively accumulated in tumor tissue after iv injection of DOXfPGPM. The DOX-fPGPM designed in this work potentially resolved the dilemma between systemic stability and rapid intracellular drug release, and would provide a promising nanomedicine platform for cancer therapy.

PEG-derivatized octacosanol as micellar carrier for paclitaxel delivery.

In this study, PEG-derivatized octacosanol copolymer was successfully developed to improve the anti-tumor activity and eliminate toxicity of the commercial formulation of paclitaxel (PTX). MPEG2K-C28, the conjugation of monomethoxy Poly(ethylene glycol) 2000 and octacosanol, was readily soluble in aqueous solution and self-assembled to form micelles with small sizes (< 20 nm) that are efficient in encapsulating PTX with a drug loading of 9.38 ± 0.18% and an encapsulation efficiency of 93.90 ± 2.12%. Meanwhile, octacosanol is very safe for humans and amazingly exhibits antitumor activity through inhibition activity of matrix metalloproteinases (MMPs) and translocation of the transcription factor (nuclear factor-kappa B, NF-κB) to the nucleus, which may be able to promote synergistic effects with PTX. A sustained and slower in vitro release behavior was observed in the (PTX micelles) than that of Taxol. PTX micelles exhibited more potent cytotoxicity than Taxol in the 4T1 breast cancer cell line. More interestingly, MPEG2K-C28 selectively inhibited the growth of 4T1 cells rather than the normal cells (HEK293 and L929 cell lines), indicating the antitumor activity of octacosanol remained after conjugation with MPEG. Acute toxicity evaluations indicated that MPEG2K-C28 was a safe drug carrier. Pharmacokinetic study revealed that PTX micelles improved the T1/2 and AUC of PTX (compared with Taxol) from 1.910 ± 0.139 h and 13.999 ± 1.109 mg/l × h to 2.876 ± 0.532 h and 76.462 ± 8.619 mg/l × h in vivo, respectively. The maximal tolerated dose (MTD) for PTX micelles (ca. 120 mg PTX/kg) in mice was significantly higher than that for Taxol (ca. 20mg PTX/kg). PTX micelles exhibited slightly better antitumor activity than Taxol but safer in 4T1 breast cancer model in vivo. The cell apoptosis in the immunofluorescent studies and the cell proliferation in the immunohistochemical studies also proved the results. In conclusion, MPEG2K-C28 is a simple, safe and effective drug delivery carrier for PTX, and has some therapeutic effects in 4T1 cells in vitro. PTX micelles showed significant antitumor activity in vivo with low systemic toxicity in 4T1 breast cancer. MPEG2K-C28 micelles entrapping PTX deserve more studies in the future.

Anti-tumor activity and safety evaluation of fisetin-loaded methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles.

Fisetin (3,3',4',7-tetrahydroxyflavone) is a potential anti-tumor agent but poor water solubility hinders its application and complicates direct parenteral administration. Nanoparticle encapsulation is an efficient way to enhance the solubility of some hydrophobic drugs. In this study, methoxy poly(ethylene glycol)-polycaprolactone (MPEG-PCL) nanoparticles were successfully prepared for fisetin delivery in vitro and in vivo. Narrow distribution fisetin-loaded MPEG-PCL NPs (aproximately100 nm) were obtained via emulsification (O/W) and displayed a sustained release behavior in vitro. Moreover, hemolysis and cell cytotoxicity testing showed that MPEG-PCL is biocompatible and safe for intravenous injection. Most importantly, NPs encapsulation enhanced the anti-cancer activity of fisetin as shown in a subcutaneous LL/2 tumor model, and reduced the hepatotoxicity of fisetin. Therefore, our data demonstrate that fisetin-loaded MPEG-PCL NPs have potential application in cancer chemotherapy.

Two novel nanoscale preparations of micelle and thermosensitive hydrogel for docetaxel to treat malignant tumor.

In this paper, two nanoscale preparations were described for docetaxel encapsulation using poly(epsilon-caprolactone)poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) copolymer as carrier for treating malignant tumor. The first formulation was docetaxel-loaded PCEC micelle (D-M), which was characterized by XRD, TEM and Malvern laser particle size and drug release studies. The highest drug-loading of docetaxel in micelle was about 22.1 +/- 1.9%, optimized average diameter and polydispersity index was 25.2 +/- 1.1 nm, 0.13 +/- 0.12, respectively. Another formulation was docetaxel-loaded PCEC thermosensitive hydrogel (D-H), which displayed special gel-sol transition behavior with body temperature. We studied the cytotoxicity and in vitro hemolytic test of blank PCEC copolymer, the result was superiority. The data of relative body weight (RW), relative tumor volume (RV) and micrographs of hematoxylin and eosin (H&E)-stained histological sections showed D-M and D-H had significant antitumor effect and exhibited different characteristics of antitumor activity. Thus, the experiments signified that the combination therapy of intravenous (i.v.) and intratumoral administration using the two formulations maybe an effective way to treat malignant tumor.