Hypercrosslinked Hydrogel Composite Membranes Targeted for Removal of Volatile Organic Compounds via Selective Solution-Diffusion in Membrane Distillation.

Membrane distillation (MD) has attracted considerable interest in hypersaline wastewater treatment. However, its practicability is severely impeded by the ineffective interception of volatile organic compounds (VOCs), which seriously affects the product water quality. Herein, a hypercrosslinked alginate (Alg)/aluminum (Al) hydrogel composite membrane is facilely fabricated via Alg pregel formation and ionic crosslinking for efficient VOC interception. The obtained MD membrane shows a sufficient phenol rejection of 99.52% at the phenol concentration of 100 ppm, which is the highest rejection among the reported MD membranes. Moreover, the hydrogel composite membrane maintains a high phenol interception (>99%), regardless of the feed temperature, initial phenol concentration, and operating time. Diffusion experiments and molecular dynamics simulation verify that the selective diffusion is the dominant mechanism for VOCs-water separation. Phenol experiences a higher energy barrier to pass through the dense hydrogel layer compared to water molecules as the stronger interaction between phenol-Alg compared with water-Alg. Benefited from the dense and hydratable Alg/Al hydrogel layer, the composite membrane also exhibits robust resistance to wetting and fouling during long-term operation. The superior VOCs removal efficiency and excellent durability endow the hydrogel composite membrane with a promising application for treating complex wastewater containing both volatile and nonvolatile contaminants.

Self-Assembly of Peptide-Lipid Nanoparticles for the Efficient Delivery of Nucleic Acids.

A transfection formulation is successfully developed to deliver nucleic acids by adding an auxiliary lipid (DOTAP) to the peptide, and the transfection efficiency of pDNA reaches 72.6%, which is close to Lipofectamine 2000. In addition, the designed KHL peptide-DOTAP complex exhibits good biocompatibility by cytotoxicity and hemolysis analysis. The mRNA delivery experiment indicates that the complex had a 9- or 10-fold increase compared with KHL or DOTAP alone. Intracellular localization shows that KHL/DOTAP can achieve good endolysosomal escape. Our design provides a new platform for improving the transfection efficiency of peptide vectors.

Nanocomposite Hydrogel Engineered Janus Membrane for Membrane Distillation with Robust Fouling, Wetting, and Scaling Resistance.

Membrane distillation (MD) is considered to be rather promising for high-salinity wastewater reclamation. However, its practical viability is seriously challenged by membrane wetting, fouling, and scaling issues arising from the complex components of hypersaline wastewater. It remains extremely difficult to overcome all three challenges at the same time. Herein, a nanocomposite hydrogel engineered Janus membrane has been facilely constructed for desired wetting/fouling/scaling-free properties, where a cellulose nanocrystal (CNC) composite hydrogel layer is formed in situ atop a microporous hydrophobic polytetrafluoroethylene (PTFE) substrate intermediated by an adhesive layer. By the synergies of the elevated membrane liquid entry pressure, inhibited surfactant diffusion, and highly hydratable surface imparted by the hydrogel/CNC (HC) layer, the resultant HC-PTFE membrane exhibits robust resistance to surfactant-induced wetting and oil fouling during 120 h of MD operation. Meanwhile, owing to the dense and hydroxyl-abundant surface, it is capable of mitigating gypsum scaling and scaling-induced wetting, resulting in a high normalized flux and low distillate conductivity at a concentration factor of 5.2. Importantly, the HC-PTFE membrane enables direct desalination of real hypersaline wastewater containing broad-spectrum foulants with stable vapor flux and robust salt rejection (99.90%) during long-term operation, demonstrating its great potential for wastewater management in industrial scenarios.

A clinical study of carbon dioxide lattice laser-assisted or microneedle-assisted 5-aminolevulinic acid-based photodynamic therapy for the treatment of hypertrophic acne scars.

OBJECTIVE: To study the clinical efficacy, recurrence rate and safety of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) combined with microneedle or CO2 lattice laser (CO2FL), in comparison with intrascar betamethasone injection in the treatment of hypertrophic acne scar. METHODS: Fifty-two patients with hypertrophic acne scars at the mandibular angle were enrolled and assigned to different therapy groups. Sixteen patients were treated with microneedle-assisted incorporation of ALA. Twenty-eight patients underwent CO2FL-assisted incorporation of ALA. Eight patients received standard therapy with intrascar injection of glucocorticoid. Two dermatologists, blinded to the therapy groups, independently evaluated the scars in all patients using the average value of the Vancouver Scar Scale score, which was treated as an integer variable. RESULTS: After three rounds of treatment, there was no significant difference in therapeutic effective rate among the microneedle, laser and topical glucocorticoid groups (93.75% vs 100% vs 100%, P = .855). One out of 16 patients (6.25%) in the microneedle group, no patient (0%) in the laser group and two out of eight patients (25%) in the topical glucocorticoid group had recurrence. The laser group showed a higher rate of adverse effects, which were usually mild and reversible, except for pigmentation. Adverse reactions could be completely subsided within 3 weeks. CONCLUSIONS: Either CO2FL or microneedle combined ALA-PDT for hypertrophic scar, as to topical glucocorticoid therapy, showed equivalent clinical effects but lower recurrence rate within 6 months of follow-up period.

Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles.

Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid-vitamin E succinate polymer (CKAAKN-HA-VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN-HA-VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN-HA-VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN-HA-VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA-VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.

Surface-Selective Grafting of Crosslinking Layers on Hydrogel Surfaces via Two Different Mechanisms of Photopolymerization for Site-Controllable Release.

This study reports an effective method for controlling substance-release sites of hydrogel. Glycidyl methacrylate, which contains two functional groups, namely, double-bond acrylate and epoxide, is photografted on a hydrogel surface through hydrogen abstraction photopolymerization due to the existence of a hydrogen donor, such as an amine, in the hydrogel matrix. The remaining epoxide group crosslinks the polymer chain of polyglycidyl methacrylate. Substance release of hydrogel is changed due to the altered surface texture of hydrogel. Rate and site-controlled substance release are achieved by controlling the thickness and site of surface grafting and the extent of epoxide ring opening. This study may provide a novel method for achieving hydrogel function or modified performance of other biomaterials to meet biological activity requirements.

Molecular insights into the adsorption and penetration of oil droplets on hydrophobic membrane in membrane distillation.

Membrane fouling induced by oily substances significantly constrains membrane distillation performance in treating hypersaline oily wastewater. Overcoming this challenge necessitates a heightened fundamental understanding of the oil fouling phenomenon. Herein, the adsorption and penetration mechanism of oil droplets on hydrophobic membranes in membrane distillation process was investigated at the molecular level. Our results demonstrated that the adsorption and penetration of oil droplets were divided into four stages, including the free stage, contact stage, spreading stage, and equilibrium stage. Due to the extensive non-polar surface distribution of the polytetrafluoroethylene (PTFE) membrane (comprising 95.41 %), the interaction between oil molecules and PTFE was primarily governed by van der Waals interaction. Continuous oil droplet membrane fouling model revealed that the new oil droplet molecules preferred to penetrate into membrane pores where oil droplets already existed. The penetration of resin (a component of medium-quality oil droplets) onto PTFE membrane pores required the "pre-paving" of light crude oil. Finally, the ΔE quantitative structure-activity relationships (QSAR) models were developed to evaluate the penetration mechanism of pollutant molecules on the PTFE membrane. This research provides new insights for improving sustainable membrane distillation technologies in treating saline oily wastewater.

Impact of nanoplastics on membrane scaling and fouling in reverse osmosis desalination process.

Nanoplastics (NPs) are a prevalent type of emerging pollutant in marine environment. However, their fouling behavior and impact on reverse osmosis (RO) membrane performance remain unexplored. We investigated the relationship between polystyrene (PS), one of the most abundant NPs, with silica scaling and humic acid (HA) fouling in RO. The results demonstrated that the surface potential of NPs played an important role in the combined scaling and fouling process. Compared with the negatively charged NPs (original PS and carboxyl group modified PS, PS-COOH), the amino-functionalized PS (PS-NH2) with positive surface charge significantly accelerated membrane scaling/fouling and induced a synergistic water flux decline, due to the strong electrostatic attraction between PS-NH2, foulants, and the membrane surface. The amino groups acted as binding sites, which promoted the heterogeneous nucleation of silica and adsorption of HA, then formed stable composite pollutants. Thermodynamic analysis via isothermal titration calorimetry (ITC) further confirmed the spontaneous formation of stable complexes between PS-NH2 and silicates/HA. Our study provides new insights into the combined NPs fouling with other scalants or foulants, and offers guidance for the accurate prediction of RO performance in the presence of NPs.

Vicious Cycle-Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis.

During liver fibrogenesis, the reciprocal crosstalk among capillarized liver sinusoidal endothelial cells (LSECs), activated hepatic stellate cells (HSCs), and dysfunctional hepatocytes constructs a self-amplifying vicious cycle, greatly exacerbating the disease condition and weakening therapeutic effect. Limited by the malignant cellular interactions, the previous single-cell centric treatment approaches show unsatisfactory efficacy and fail to meet clinical demand. Herein, a vicious cycle-breaking strategy is proposed to target and repair pathological cells separately to terminate the malignant progression of liver fibrosis. Chondroitin sulfate-modified and vismodegib-loaded nanoparticles (CS-NPs/VDG) are designed to efficiently normalize the fenestrae phenotype of LSECs and restore HSCs to quiescent state by inhibiting Hedgehog signaling pathway. In addition, glycyrrhetinic acid-modified and silybin-loaded nanoparticles (GA-NPs/SIB) are prepared to restore hepatocytes function by relieving oxidative stress. The results show successful interruption of vicious cycle as well as distinct fibrosis resolution in two animal models through multiregulation of the pathological cells. This work not only highlights the significance of modulating cellular crosstalk but also provides a promising avenue for developing antifibrotic regimens.

Preparation and Characterization of PLGA-based Magnetic Polymer Nanoparticles for Targeting Pancreatic Adenocarcinoma.

AIMS: This study aims to develop a novel tumor-targeted molecular probe for pancreatic cancer imaging. The objective of this is to prepare a CKAAKN peptide-conjugated poly (lactic-co-glycolic acid)-poly (ethylene glycol) amphiphilic polymer (CKAAKN-PEG-PLGA) for the tumor-targeted delivery of magnetic resonance imaging (MRI) contrast agent ultrasmall superparamagnetic iron oxide (USPIO). BACKGROUND: The early diagnosis of pancreatic cancer is crucial for improving its prognosis, but the clinical application of many diagnostic methods is limited owing to a lack of specificity and sensitivity. METHODS: CKAAKN-PEG-PLGA was synthesized by the amidation reaction. USPIO-loaded polymeric magnetic nanoparticles (USPIO@CKAAKN-PEG-PLGA) were prepared by the emulsion solvent evaporation method. The in vitro tumor targeting and bio-safety of nanoparticles were evaluated by targeted cellular uptake, MR imaging and MTT assay. RESULTS: USPIO@CKAAKN-PEG-PLGA nanoparticles showed excellent biosafety with an average diameter of 104.5 ± 4.1 nm. Modification of CKAAKN peptide could improve USPIO binding ability to internalize into CKAAKN-positive BxPC-3 cells compared with non-targeting nanoparticles and the control group. The relative fluorescence intensity in BxPC-3 and HPDE6-C7 cells was 23.77 ± 4.18 and 6.44 ± 2.10 (p < 0.01), and respectively became 16.13 ± 0.83 and 11.74 ± 1.74 after the addition of free CKAAKN peptide. In vitro MR imaging studies showed that an obvious decrease in the signal intensity was observed in the targeted nanoparticles group incubated with BxPC-3 and HPDE6-C7 cells (p < 0.05). CONCLUSION: USPIO@CKAAKN-PEG-PLGA nanoparticles could significantly enhance the tumor specificity of USPIO in CKAAKN-positive pancreatic cancer cell BxPC-3, which is expected as a promising candidate of MRI contrast enhancement for the early diagnosis of pancreatic cancer.

Study on the Slow-Release Mometasone Furoate Injection of PLGA for the Treatment of Knee Arthritis.

PURPOSE: The purpose of this study is to develop a new PLGA based formulation for microspheres, which aims to release mometasone furoate for one month, so as to improve compliance. METHODS: The microspheres containing mometasone furoate were prepared by oil in water emulsion and solvent evaporation. The microspheres were characterized by surface morphology, shape, size and encapsulation efficiency. The release in vitro was studied in 37°C phosphate buffer, and in vivo, pharmacodynamics and preliminary safety evaluation were conducted in male Sprague Dawley rats. RESULTS: The morphology results showed that the microspheres have a smooth surface, spherical shape and an average diameter of 2.320-5.679µm. The encapsulation efficiency of the microspheres loaded with mometasone furoate was in the range of 53.1% to 95.2%, and the encapsulation efficiency of the microspheres could be greatly affected by the proportion of oil phase to the water phase and other formulation parameters. In vitro release kinetics revealed that drug release from microspheres was through non-Fick's diffusion and PLGA polymer erosion. Pharmacokinetic data showed that the initial release of microspheres was small and then sustained. The results of the pharmacodynamics study fully proved the long-term effectiveness of mometasone furoate microspheres. The results of in vivo safety evaluation showed that the preparation system possessed good in vivo safety. CONCLUSION: This study shows that the microspheres prepared in this study have sufficient ability to stable drug release at least for 35 days, with good efficacy and high safety. In addition, mometasone furoate can be used as a potential candidate drug for 35 days long-term injection.

pH and ROS sequentially responsive podophyllotoxin prodrug micelles with surface charge-switchable and self-amplification drug release for combating multidrug resistance cancer.

Multidrug resistance (MDR) is one of the main reasons for tumor chemotherapy failure. Podophyllotoxin (PPT) has been reported that can suppress MDR cancer cell growth; however, effective delivery of PPT to MDR cancer cells is challenged by cascaded bio-barriers. To effectively deliver PPT to MDR cancer cells, a PPT polymeric prodrug micelle (PCDMA) with the charge-conversion capability and self-acceleration drug release function are fabricated, which is composed of a pH and reactive oxygen species (ROS) sequentially responsive PPT-polymeric prodrug and an ROS generation agent, cucurbitacin B (CuB). After reach to tumor tissue, the surface charge of PCDMA could rapidly reverse to positive in the tumor extracellular environment to promote cellular uptake. Subsequently, the PCDMA could be degraded to release PPT and CuB in response to an intracellular high ROS condition. The released CuB is competent for generating ROS, which in turn accelerates the release of PPT and CuB. Eventually, the released PPT could kill MDR cancer cells. The in vitro and in vivo studies demonstrated that PCDMA was effectively internalized by cancer cells and produces massive ROS intracellular, rapid release drug, and effectively overcame MDR compared with the control cells, due to the tumor-specific weakly acidic and ROS-rich environment. Our results suggest that the pH/ROS dual-responsive PCDMA micelles with surface charge-reversal and self-amplifying ROS-response drug release provide an excellent platform for potential MDR cancer treatment.

Spatiotemporally programmable cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery.

DNA nanostructures have been demonstrated as promising carriers for gene delivery. In the carrier design, spatiotemporally programmable assembly of DNA under nanoconfinement is important but has proven highly challenging due to the complexity-scalability-error of DNA. Herein, a DNA nanotechnology-based strategy via the cascade hybridization chain reaction (HCR) of DNA hairpins in polymeric nanoframework has been developed to achieve spatiotemporally programmable assembly of DNA under nanoconfinement for precise siRNA delivery. The nanoframework is prepared via precipitation polymerization with Acrydite-DNA as cross-linker. The potential energy stored in the loops of DNA hairpins can overcome the steric effect in the nanoframework, which can help initiate cascade HCR of DNA hairpins and achieve efficient siRNA loading. The designer tethering sequence between DNA and RNA guarantees a triphosadenine triggered siRNA release specifically in cellular cytoplasm. Nanoframework provides stability and ease of functionalization, which helps address the complexity-scalability-error of DNA. It is exemplified that the phenylboronate installation on nanoframework enhanced cellular uptake and smoothed the lysosomal escape. Cellular results show that the siRNA loaded nanoframework down-regulated the levels of relevant mRNA and protein. In vivo experiments show significant therapeutic efficacy of using siPLK1 loaded nanoframework to suppress tumor growth.

Improving efficiency of traveling wave rotary ultrasonic motor by optimizing stator.

The application of ultrasonic motor (USM) has been seriously restricted by its relatively low efficiency. The energy loss caused by the radial sliding on the contact surface of the motor is considered as one of the major reasons for the low efficiency of USM. In this report, the solution is proposed to reduce the radial sliding by optimizing the stator comb-teeth of the traveling wave rotary ultrasonic motor (TWUSM). Theoretical analysis, simulation, and experiments were conducted in PMR60 type TWUSM (motor model) to verify the optimized method. The results indicate that the friction angle α, which represents the degree of radial sliding, can be efficiently reduced by chamfering the teeth on the stator of motor. The maximum efficiency of 44.3% is obtained in the modified motor of which the stator chamfer size is 1.0 mm × 45°, which is nearly two times higher than that of the nonmodified motor (25%). Therefore, it is a feasible and simple pathway to improve the efficiency of the USM.