Natural bioactive compounds exhibit significant antioxidant and anti-inflammatory activities, offering a promising natural alternative or complement to current immunosuppressive therapies for ulcerative colitis (UC). However, achieving effective colon-targeted delivery of these compounds remains a significant challenge due to premature drug release and limited local retention. In this study, we present a nanoparticle-hydrogel composite system, BZH@HCE, designed to enhance the therapeutic efficacy of baicalein (BA) for UC treatment. Zein and oxidized hyaluronic acid-based nanoparticles (BZH) provide a high loading capacity for BA and prevent premature drug release in the upper gastrointestinal tract. BZH encapsulation within an epigallocatechin gallate (EGCG)-containing hydrogel matrix (HCE) further sustains BA release and amplifies its antioxidant and anti-inflammatory effects through synergistic action with EGCG. The adhesive hydrogel matrix ensures prolonged colon retention for up to 24 hours in colitis mice. In vivo studies using a dextran sulfate sodium-induced murine colitis model demonstrate that BZH@HCE significantly alleviates intestinal inflammation, promotes epithelial barrier repair, and shows excellent biocompatibility, outperforming both free BA and BZH nanoparticles. These findings position BZH@HCE as a versatile and effective platform for UC therapy, highlighting its potential as a natural, bioactive compound-based treatment.
Boosting the trivalent/divalent metal (M3+/M2+) redox pair in 3d metal compounds (TMCs) can facilitate the surface reconstruction during the oxygen evolution reaction (OER), transforming TMCs into trivalent metal oxyhydroxide (MOOH) species, which has been demonstrated to be the essential phase of the active substance. Herein, we examined an indirect strategy by the proof-of-concept of cobalt phosphide (CoP), that is, leveraging the strong substrate effect of Ti3C2Tx MXene to boost the Co3+/Co2+ pair, validated by X-ray absorption near-edge spectroscopy (XANES). The resulting CoP@Ti3C2Tx electrocatalyst achieves an ultralow overpotential of 218 mV at 10 mA cm-2 and a small Tafel slope of 52 mV dec-1 on the glassy carbon electrode and can operate stably over 500 h in a water electrolyzer, outperforming most non-noble metal electrocatalysts. Operando attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS), operando Raman spectra, and theoretical calculations reveal an adsorbate evolution mechanism (AEM) for CoP@Ti3C2Tx, suggesting the high activity typically associated with lattice oxygen-mediated mechanism (LOM) catalysts while inheriting the excellent stability of AEM-driven systems. This work highlights substrate engineering as an effective indirect strategy to boost the M3+/M2+ pair, providing a paradigm for designing OER electrocatalysts with both high activity and long-term stability.
Hemostasis is the initial step in wound healing, yet significant challenges, such as massive bleeding and infection, often arise. In this study, we developed amphiphilic biodegradable polyester-based segmented polyurethane (SPU) microspheres modified with epigallocatechin gallate (EGCG)-Ag nanoparticles and calcium-alginate cross-linking shell, combining blood absorption with the pro-coagulation properties of Ca2+ and the negative charge of EGCG for synergistic hemostatic effects across various stages of the coagulation cascade. The in vitro blood clotting time of the SPU@EAg@CaAlg microsphere (328.7 s) was reduced by half compared to the SPU microsphere (685.0 s). SPU@EAg@CaAlg exhibited a reduced hemostatic time and blood loss in three rat hemostatic models. Additionally, EGCG-Ag nanoparticles imparted strong antibacterial and anti-inflammatory properties both in vitro and in vivo. In vivo infected wound model demonstrated that SPU@EAg@CaAlg effectively eliminated bacteria and reduced the levels of pro-inflammatory factors, thereby promoting wound healing. Thus, the modified SPU microspheres present a promising candidate for effective hemostatic applications.
The pathogenesis of inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn's disease is extremely cloudy. Maintaining the level of remission lesions in colitis is the default treatment attitude at present. Epithelial barrier restoration is considered as the same important strategy as colonic targeted drug delivery in UC treatment. In this paper, we developed a multilayer natural polysaccharide microsphere (pectin/chitosan/alginate) with pH and enzyme dual sensitivity to reduce the loss of medication in the upper digestive tract and preferentially adhere to exposed epithelial cells in colonic tissues by electrostatic forces for efficiently targeted UC treatment. Olsalazine as an inflammatory drug was efficiently loaded in the chitosan layer and realized a colonic pH-responsive drug release. Furthermore, the multilayer microspheres exhibited excellent capability in suppressing harmful flora and a bio-adhesion effect to extend the duration of local medicine. In the in vivo anti-colitis study, the downregulated levels of pro-inflammatory factors and the increase of tight junction protein indicated the excellent anti-inflammation effect of the olsalazine-loaded microspheres. In summary, these results showed that the multilayer natural polysaccharide microspheres could be a powerful candidate in the targeted drug delivery system for UC therapy.
Due to the low melt strength, PET foam cells easily grow, and due to the low CO2 concentration in PET, generating more nucleation sites during the foaming process is difficult. As a result, PET foam produced using the supercritical CO2 foaming method possesses a large cell size and a low expansion ratio, which leads to poor mechanical performance. In addition, there has not been much research on how to improve CO2 concentration in PET. In this work, the PC with higher melt strength and CO2 absorption capacity was incorporated into the PET matrix to improve the foaming behaviors of the blend. The results showed that the melt strength and CO2 concentration of PET/PC blends are much higher than that of pure PET. For instance, the melt strength and CO2 concentration of the PET/PC10 blend would be more than twice that of pure PET when the PC content is only 10%wt. By studying the foaming behavior, it was found that high melt strength inhibited the cell overgrowth and collapse of PET/PC foam, resulting in the foam with good cell structure was obtained. In addition, the high CO2 concentration in PET/PC blend is conducive to cell nucleation, thereby increasing the foam expansion ratio during the CO2 foaming process. Finally, the PET/PC blend foam with excellent mechanical properties was obtained. To be specific, the expansion ratio of the PET/PC blend foam was about 9.61, and the average cell size was only 40.38 mu m. And the PET/PC blend foam possessed an excellent compressive strength of 7.41 MPa due to the strong interfacial bead cohesion, which showed the application prospect in the field of construction engineering.
Electrocatalytic hydrogen peroxide (H2 O2 ) synthesis via the two-electron oxygen reduction reaction (2e ORR) pathway is becoming increasingly important due to the green production process. Here, cationic vacancies on nickel phosphide, as a proof-of-concept to regulate the catalyst's physicochemical properties, are introduced for efficient H2 O2 electrosynthesis. The as-fabricated Ni cationic vacancies (VNi )-enriched Ni2-x P-VNi electrocatalyst exhibits remarkable 2e ORR performance with H2 O2 molar fraction of >95% and Faradaic efficiencies of >90% in all pH conditions under a wide range of applied potentials. Impressively, the as-created VNi possesses superb long-term durability for over 50 h, suppassing all the recently reported catalysts for H2 O2 electrosynthesis. Operando X-ray absorption near-edge spectroscopy (XANES) and synchrotron Fourier transform infrared (SR-FTIR) combining theoretical calculations reveal that the excellent catalytic performance originates from the VNi -induced geometric and electronic structural optimization, thus promoting oxygen adsorption to the 2e ORR favored "end-on" configuration. It is believed that the demonstrated cation vacancy engineering is an effective strategy toward creating active heterogeneous catalysts with atomic precision.
The anti-biofouling properties have important applications in the medical field. In this study, cross-linked networks were prepared by photopolymerizing two synthetic macromonomers, including fumaric acid monoethyl ester (FAME) functionalized, three-armed poly(l-lactide) prepolymers (3-PLLA-F) and poly(ε-caprolactone) prepolymers (2-PCL-F), with N-vinyl-2-pyrrolidone (NVP) as the diluent. The prepared networks were characterized by their thermal properties, mechanical properties, cytotoxicity experiments and anti-biofouling properties. The Young's modulus and tensile strength of networks decreased by increasing PCL content. In contrast, the elongation of networks significantly increased. Moreover, no obvious cytotoxicity was observed, and the adhesion of L929 fibroblasts and platelets was resisted. Combined with Digital Light Processing technology (DLP) in the future, the designed polymer network could potentially be commercial in the field of biological anti-fouling materials.
研究开发高效且快捷的止血材料一直是科学研究者研究的重点课题.本文利用交联反应制备了一种新型淀粉基止血粉.研究结果表明红外光谱和表面元素分析验证了交联反应的进行.当反应时间为90min,交联剂含量为2%时,反应温度为70℃时,止血粉本身网状交联结构具有较高的吸水倍率和较快的吸水速度.止血粉的研究结果具有很高的应用推广价值.
采用丙三醇开环聚合左旋丙交酯(L-LA),合成了三臂乳酸预聚物(PLLA 3),通过与封端剂富马酸单乙酯(FAME)的酯化反应,成功地合成光敏性三臂乳酸预聚物(PLLA 3-FAME).将PLLA 3-FAME与反应性稀释剂N-乙烯基吡咯烷酮(NVP)和光引发剂Irgacure 2959,混合调制成光敏性聚(乳酸-乙烯基吡咯烷酮)树脂,经紫外光固化后成功成型,得到聚(乳酸-乙烯基吡咯烷酮)材料,并对材料结构和性能进行了表征测试.结果 表明,较材料PLLA相比,聚(乳酸-乙烯基吡咯烷酮)材料的亲水性、拉伸强度和降解速度均有显著提升.水接触角由91°±2°下降至75°±4°,吸水率由0.43%提升至35%;拉伸强度和延伸率分别由28 MPa,3.82%提升至77 MPa,11.35%;24周内的降解速度由未发生降解提升至质量损失27.57%.该材料可作为3D打印基材,可用于定制要求和组织工程的材料领域.
In this study, we reported a nanocomplex (PAF) of PEGylated polygalacturonic acid, 5,10,15,20-tetrakis (4-aminophenyl) porphyrin (TAPP), and Fe3+ for photodynamic therapy (PDT)-enhanced ferroptosis in cancer treatment. PAF exhibited a size of 135nm and a TAPP and Fe3+ loading content of 6.99 and 0.77%, respectively. The singlet oxygen (1O2) generation capacity of TAPP can be activated and significantly enhanced at acidic pH (4.5–5.0). Besides, the enhanced near-infrared absorption of TAPP at acidic pH enabled a further increase in 1O2 generation capability by a near-infrared laser (760 nm). The polysaccharide-based polymer carrier offers excellent biocompatibility, and PAF displayed a proliferative effect in both normal (L929) and cancer (B16) cells. However, upon light irradiation, PAF exhibited high toxicity to B16 melanoma cells by intracellular reactive oxygen species elevation, glutathione depletion, and lipid peroxidation. PAF displayed a much better anticancer effect than the nanocomplex containing Fe3+ or TAPP alone, indicating the PDT-enhanced ferroptosis in PAF. This study suggested that PDT-enhanced ferroptosis could be a facile and robust strategy of nanotherapeutics with high potency, tumor selectivity, and excellent biocompatibility.
Tonalide (AHTN) is a new category of pollutants with a wide range of potential environmental and organismal hazards due to its persistence and lipophilicity, and the safety evaluation of this pollutant under physiological condition is a pressing issue. This study investigated the mechanism of interaction between AHTN and human serum albumin (HSA) that is an important transporter in plasma using multiple spectroscopic, molecular docking, and dynamics simulation methods. The steady-state fluorescence and fluorescence lifetime experiments showed that AHTN quenches the inherent fluorescence of HSA through a static quenching mechanism. Thermodynamic parameters exhibited that the binding constant of AHTN and HSA is of the order of 10^4 L/mol, and the binding is a spontaneous process of moderate strength with hydrophobic forces as the main driving force. Site competition revealed that AHTN binds to site I of HSA IIA subdomain, which was evidenced by the molecular docking results. AHTN altered the HSA amino acid microenvironment and conformation can be derived from three-dimensional fluorescence, circular dichroism spectroscopy, and molecular dynamics simulation. The computer simulations corroborate the experimental results positively. Moreover, AHTN acted as a competitive inhibitor to weaken the esterase-like activity of HSA, leading to impaired function of HSA. Results suggest that interactions between AHTN and HSA may affect the normal structure and activities of the protein, this insight will be helpful to provide some basic information to further explore the potential hazards of AHTN in humans.
Synthetic, biodegradable polymers hold great potential in dura mater substitution. In this study, a dura mater-mimetic double-layer film@sponge composite was developed. The composite contains a poly(caprolactone-co-lactide) (PCLA) film and polyurethane (PU) sponge, which simulates the hard and soft layers of dura mater, respectively. PCLA films were prepared by a solution-casting method and showed excellent mechanical properties and tolerance to water. PU sponge was hydrophilic and had a high water-absorption rate (about 500%). The double-layer composite (film@sponge) integrated the good mechanical properties of the films and the good water absorption of the sponge. The excellent biocompatibility and biodegradability of the PCLA film@PU sponge composites were verified by in vitro degradation and cytotoxicity study and the in vivo implantation in the back of rats. Importantly, the film@sponge composite had a suitable degradation rate and good biocompatibility, holding potential in the field of dural repair.
部分液化天然气(LNG)接收站在投运初期无外输管网,蒸发气(BOG)只能通过增压后再液化的方式进行回收,目前主要有3种再液化工艺.为了解决再液化工艺领域存在的问题,以两种增压选型方案和3种再液化制冷路线为基础组合成6种可能方案,根据某LNG接收站的实际数据,从工艺流程、操作性能、技术垄断性、能耗及投资等方面对各方案进行了对比分析,并按该站再液化单元运行年限要求进行了投资-运行总费用比较,由此确定采用第一级可耐低温的BOG增压机的混合冷剂制冷再液化工艺流程方案.然后,收集并给出了国内接收站已投运的BOG再液化回收装置情况统计表,进一步验证了混合冷剂制冷再液化工艺流程占主导的分析.最后,结合以往项目经验,介绍了再液化工艺设计中受接收站约束的限制条件.所研究结论可为后来设计者提供重要的思路和参考.
Pollution caused by waste plastic, particularly from the foam packages, is increasingly worse, and utilizing biodegradable material is considered a promising solution to handle this environmental issue. Poly (butylene adipate-co-terephthalate) (PBAT) is a typical environment-friendly polymer due to the recognized biodegradability and excellent mechanical performance. However, there have been very few works preparing PBAT bead foams via the supercritical fluid foaming technology, and the related foaming behavior is still unclear. In this study, we foamed PBAT and PBAT-polylactide (PLA) beads using supercritical carbon dioxide (Sc-CO2) as a foaming agent, and the foaming behaviors of beads as well as the mechanical properties of bead foam parts manufactured by one-step foaming method were systematically investigated. The incorporation of PLA enhanced the mechanical properties of the composition. At the optimal foaming conditions, the expansion ratio and cell density of PBAT/PLA foam were 13.44 and 4.08 x 10(8) cells/cm(3), respectively. Benefitting from the uniform cell structure, the bead foam part showed excellent resilience and elasticity with adhesive strength of 0.57 MPa and compression strength of 1.05 MPa. Meanwhile, PBAT and PBAT-PLA foam parts had high surface quality and good interbead sintering properties. PBAT can be a promising substitute for traditional non-polymer foams for packaging, household, and automobile fields.
A three-armed star-shaped poly(l-lactide) (PLLA) oligomer was synthesized using glycerol to ring-opening and polymerize l-lactide. The resultant oligomer introduced photoreactive groups at the terminal of PLLA chains by a coupling reaction with monoethyl fumarate (FAME). Photopolymerizable resin has been prepared by mixing PLLA 3-FAME, N-vinyl-2-pyrrolidone (NVP) as a reactive diluent and Irgacure 2959 as a photoinitiator. The PLLA 3-FAME/NVP cross-linked network could be formed by UV curing and was characterized through mechanical property tests, cytotoxicity experiments and cell adhesion experiments. In the dry state, Young's modulus and tensile strength of the network were significantly higher than those of pure PLLA formed by fused deposition modeling (FDM) printing, due to the formation of the cross-linked net. In the wet state, however, Young's modulus and tensile strength of the network were reduced by less than those of PLLA since the water-absorbed NVP content was easy to stretch. Moreover, the resultant network not only exhibited no obvious cytotoxicity but also resisted the adhesion of L929 fibroblasts. Combined with Digital Light Processing (DLP) technology, the poly(l-lactide-b-N-vinyl-2-pyrrolidone) network may be widely used in the field of anti-adhesion barrier materials and/or biological anti-fouling materials with customization requirements.
Doxorubicin (DOX) is a widely-used anticancer drug, but its cardiotoxicity severely hampers its potency in chemotherapy. Herein, human serum albumin (HSA) is engaged as a biocompatible nanocarrier to load a pH-sensitive DOX prodrug, DMDOX, generating HSA-DMDOX nanoparticles via self-assembly driven by hydrophobic interactions. HSA-DMDOX disperses well in a physiological environment (∼40 nm) but aggregates in a tumor acidic microenvironment (pH 6.5, ∼140 nm) owing to the hydrophobicity increase of DMDOX by protonation of carboxylic groups. In vitro anticancer study showed that HSA-DMDOX exhibited enhanced cellular uptake by 4T1 cells and superior cytotoxicity in comparison to HSA-DOX nanoparticles. In vivo study suggested that HSA-DMDOX achieved long blood circulation, aggregation enhanced tumor retention, comparable antitumor efficacy and reduced cardiotoxicity relative to free DOX. Our work presents a facile and effective approach to delivering anthracyclines by HSA-based tumor pH-responsive nanoparticles with aggregation-enhanced tumor retention and reduced toxicity.
Correction for 'Combination of PEG-decorated black phosphorus nanosheets and immunoadjuvant for photoimmunotherapy of melanoma' by Shiyu Wan et al., J. Mater. Chem. B, 2020, 8, 2805-2813.
Molecular targeted-photodynamic combinational therapy is a promising strategy to enhance antitumor effects; meanwhile, current nanocarriers face challenges of limited selective delivery and release of therapeutic agents to specific tumor sites, which significantly compromises their therapeutic efficacy. Herein, we report active-targeting, enzyme- and ROS-dual responsive nanoparticles (HPGBCA) consisting of CD44-targeting hyaluronic acid (HA) shells and afatinib (AFT)-loaded, ROS-sensitive poly(l-lysine)-conjugated chlorin e6 (Ce6) derivative nanoparticle cores (PGBCA). HPGBCA can actively carry AFT and Ce6 specifically to tumor cells due to the negatively charged HA and CD44-mediated active targeting. Subsequently, hyaluronidase in the endosome will further spur the degradation of the HA shell to prompt exposure of the positively charged PGBCA core for rapid endosomal escape and intracellular delivery of AFT and Ce6. Furthermore, the generation of ROS produced by Ce6 under NIR irradiation can trigger the rapid oxidation of the thioether linker to facilitate the release of AFT into the cytoplasm. In vitro and in vivo studies demonstrated that the released AFT and excessive ROS at the local site can synergistically induce cell apoptosis to enhance the therapeutic efficacy without side effects. Our developed intelligent nanoparticle provides new avenues to achieve on-demand, specific intracellular drug release for improved molecular targeted-photodynamic combination therapeutic efficacy.
Challenges associated with low-drug-loading capacity, lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy. Herein, we constructed active-targeting, redox-activated polymeric micelles (HPGssML) self-assembled aptamer-decorated, amphiphilic biodegradable poly (benzyl malolactonate-co-epsilon-caprolactone) copolymer with disulfide linkage and pi-conjugated moieties. HPGssML with a homogenous spherical shape and nanosized diameter (similar to 150nm) formed a low critical micellar concentration (10(-3)mg/mL), suggesting good stability of polymeric micelles. The anticancer drug, doxorubicin (DOX), can be efficiently loaded into the core of micelles with high-drug-loading content via strong pi-pi interaction, which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles. The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment. Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells. An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration (IC50) of DOX-loaded HPGssML was two times lower than that of the control group, demonstrating improved antitumor efficacy. Therefore, the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.
Photoimmunotherapy, which combines local photothermal therapy (PTT) with immunological stimulation, is a promising modality for cancer treatment. Herein, we have reported a photothermal-immunotherapy of melanoma using pegylated black phosphorus nanosheets (BP-PEG NSs) and imiquimod (R837) as the photothermal conversion agent and the immunoadjuvant, respectively. The photothermal stability of BP NSs was remarkably enhanced after the modification of poly(ethylene glycol) (PEG) by electrostatic interactions. The in situ generation of tumor-associated antigens by PTT elicited a strong immune response in the presence of R837, achieving a photoimmunotherapy of B16 melanoma. This photoimmunotherapy stimulated a stronger immune response both in vitro and in vivo than monotherapy, inducing a much greater release of cytokines such as IL-6, IL-12, and TNF-α. In vivo antitumor studies in B16 tumor-bearing mice demonstrated that photoimmunotherapy showed the best tumor inhibition effects. Our study suggested that BP-PEG NS-based PTT primed with an immunoadjuvant can be used for synergistic photoimmunotherapy of melanomas.