Porous Waterborne Polyurethane Films Templated from Pickering Foams for Fabrication of Synthetic Leather.

Waterborne polyurethane (WPU) latex nanoparticles with proven interfacial activity were utilized to stabilize air-water interfaces of Pickering foams through interfacial interaction with hydrophobic fumed silica particles (SPs). The rheological properties of the Pickering foam were tailored through adjustment of their SP content, which influenced their formability and stability. A Pickering foam stabilized with WPU and SPs was used as a template to prepare a WPU-SP composite porous film. The as-prepared film had intact open-cell porous structures, which increased its water absorption and water-vapor permeability. The porous film was used as a middle layer in the preparation of synthetic leather via a four-step "drying method". Compared with commercial synthetic leather, the lab-made synthetic leather with a middle layer made of the WPU-SP composite porous film exhibited a richer porous structure, acceptable wetting on a fabric substrate, a thicker porous layer, and higher water-vapor permeability. This work provides a novel and facile approach for preparing WPU-SP Pickering foams. Furthermore, the foams have the potential to function as a sustainable material for creating a porous-structured synthetic leather made from WPU, which may be utilized as an alternative to solvent-based synthetic leather.

Engineering poly(ethylene glycol) particles for targeted drug delivery.

Poly(ethylene glycol) (PEG) is considered to be the "gold standard" among the stealth polymers employed for drug delivery. Using PEG to modify or engineer particles has thus gained increasing interest because of the ability to prolong blood circulation time and reduce nonspecific biodistribution of particles in vivo, owing to the low fouling and stealth properties of PEG. In addition, endowing PEG-based particles with targeting and drug-loading properties is essential to achieve enhanced drug accumulation at target sites in vivo. In this feature article, we focus on recent work on the synthesis of PEG particles, in which PEG is the main component in the particles. We highlight different synthesis methods used to generate PEG particles, the influence of the physiochemical properties of PEG particles on their stealth and targeting properties, and the application of PEG particles in targeted drug delivery.

mRNA-Laden Lipid-Nanoparticle-Enabled in Situ CAR-Macrophage Engineering for the Eradication of Multidrug-Resistant Bacteria in a Sepsis Mouse Model.

Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsis-associated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ, yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the "superbug" MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.

Decoding Macrophage Subtypes to Engineer Modulating Hydrogels for the Alleviation of Intervertebral Disk Degeneration.

A major pathological basis for low back pain is intervertebral disk degeneration, which is primarily caused by the degeneration of nucleus pulposus cells due to imbalances in extracellular matrix (ECM) anabolism and catabolism. The phenotype of macrophages in the local immune microenvironment greatly influences the balance of ECM metabolism. Therefore, the control over the macrophage phenotype of the ECM is promising to repair intervertebral disk degeneration. Herein, the preparation of an injectable nanocomposite hydrogel is reported by embedding epigallocatechin-3-gallate-coated hydroxyapatite nanorods in O-carboxymethyl chitosan cross-linked with aldehyde hyaluronic acid that is capable of modulating the phenotype of macrophages. The bioactive components play a primary role in repairing the nucleus pulposus, where the hydroxyapatite nanorods can promote anabolism in the ECM through the nucleopulpogenic differentiation of mesenchymal stem cells. In addition, epigallocatechin-3-gallate can decrease catabolism in the ECM in nucleus pulposus by inducing M2 macrophage polarization, which exists in normal intervertebral disks and can alleviate degeneration. The nanocomposite hydrogel system shows promise for the minimally invasive and effective treatment of intervertebral disk degeneration by controlling anabolism and catabolism in the ECM and inhibiting the IL17 signaling pathway (M1-related pathway) in vitro and in vivo.

Intracavitary Spraying of Nanoregulator-Encased Hydrogel Modulates Cholesterol Metabolism of Glioma-Supportive Macrophage for Postoperative Glioblastoma Immunotherapy.

Glioblastoma multiforme (GBM) is notoriously resistant to immunotherapy due to its intricate immunosuppressive tumor microenvironment (TME). Dysregulated cholesterol metabolism is implicated in the TME and promotes tumor progression. Here, it is found that cholesterol levels in GBM tissues are abnormally high, and glioma-supportive macrophages (GSMs), an essential "cholesterol factory", demonstrate aberrantly hyperactive cholesterol metabolism and efflux, providing cholesterol to fuel GBM growth and induce CD8+ T cells exhaustion. Bioinformatics analysis confirms that high 7-dehydrocholesterol reductase (DHCR7) level in GBM tissues associates with increased cholesterol biosynthesis, suppressed tumoricidal immune response, and poor patient survival, and DHCR7 expression level is significantly elevated in GSMs. Therefore, an intracavitary sprayable nanoregulator (NR)-encased hydrogel system to modulate cholesterol metabolism of GSMs is reported. The degradable NR-mediated ablation of DHCR7 in GSMs effectively suppresses cholesterol supply and activates T-cell immunity. Moreover, the combination of Toll-like receptor 7/8 (TLR7/8) agonists significantly promotes GSM polarization to antitumor phenotypes and ameliorates the TME. Treatment with the hybrid system exhibits superior antitumor effects in the orthotopic GBM model and postsurgical recurrence model. Altogether, the findings unravel the role of GSMs DHCR7/cholesterol signaling in the regulation of TME, presenting a potential treatment strategy that warrants further clinical trials.

Restoring neuronal iron homeostasis revitalizes neurogenesis after spinal cord injury.

Spinal cord injury (SCI) can lead to iron overloading and subsequent neuronal ferroptosis, which hinders the recovery of locomotor function. However, it is still unclear whether the maintenance of neuronal iron homeostasis enables to revitalize intrinsic neurogenesis. Herein, we report the regulation of cellular iron homeostasis after SCI via the chelation of excess iron ions and modulation of the iron transportation pathway using polyphenol-based hydrogels for the revitalization of intrinsic neurogenesis. The reversed iron overloading can promote neural stem/progenitor cell differentiation into neurons and elicit the regenerative potential of newborn neurons, which is accompanied by improved axon reinnervation and remyelination. Notably, polyphenol-based hydrogels significantly increase the neurological motor scores from ~8 to 18 (out of 21) and restore the transmission of sensory and motor electrophysiological signals after SCI. Maintenance of iron homeostasis at the site of SCI using polyphenol-based hydrogels provides a promising paradigm to revitalize neurogenesis for the treatment of iron accumulation-related nervous system diseases.

Ultrasound-Assisted Encapsulation of Phytochemicals for Food Applications: A Review.

The use of phytochemicals as natural food additives is a topic of interest for both academic and food industry communities. However, many of these substances are sensitive to environmental conditions. For this reason, encapsulation is usually performed prior to incorporation into food products. In this sense, ultrasound-assisted encapsulation is an emerging technique that has been gaining attention in this field, bringing important advantages for the production of functional food products. This review article covered applications published in the last five years (from 2019 to 2023) on the use of ultrasound to encapsulate phytochemicals for further incorporation into food. The ultrasound mechanisms for encapsulation, its parameters, such as reactor configuration, frequency, and power, and the use of ultrasound technology, along with conventional encapsulation techniques, were all discussed. Additionally, the main challenges of existing methods and future possibilities were discussed. In general, ultrasound-assisted encapsulation has been considered a great tool for the production of smaller capsules with a lower polydispersity index. Encapsulated materials also present a higher bioavailability. However, there is still room for further developments regarding process scale-up for industrial applications. Future studies should also focus on incorporating produced capsules in model food products to further assess their stability and sensory properties.

Biomimetic Hemostatic Powder Derived from Coacervate-Immobilized Thermogelling Copolymers.

Intrinsic hemostasis is an innate body response to prevent bleeding based on the sol-gel transition of blood. However, it is often inadequate for exceptional situations, such as acute injury and coagulation disorders, which typically require immediate medical intervention. Herein, we report the preparation of an efficient hemostatic powder, composed of tannic acid (TA), poly(ethylene glycol) (PEG), and poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) triblock copolymer (TB), for biomimetic hemostasis at the bleeding sites. TA has a high affinity for biomolecules and cells and can form coacervates with PEG driven by hydrogen bonding. TB enhances the mechanical strength and provides thermoresponsiveness. The hemostatic powder can rapidly transit into a physical and biodegradable seal on wet substrates under physiological conditions, demonstrating its promise for the generation of instant artificial clots. Importantly, this process is independent of the innate blood clotting process, which could benefit those with blood clotting disorders. This biomimetic hemostatic powder is an adaptive topical sealing agent for noncompressible and irregular wounds, which is promising for biomedical applications.

Cascade Reaction of Thiol-Disulfide Exchange Potentiates Rapid Fabrication of Polymer Hydrogels.

We report a rapid cross-linking strategy for the fabrication of polymer hydrogels based on a thiol-disulfide cascade reaction. Specifically, thiolated polymers (e.g., poly(ethylene glycol), hyaluronic acid, sodium alginate, poly(acrylic acid), and poly(methylacrylic acid)) can be cross-linked via the trigger of Ellman's reagent, resulting in the rapid formation of hydrogels over 20-fold faster than that via the oxidation in air. The gelation kinetics of hydrogels can be tuned by varying the polymer concentration and the molar ratio of Ellman's reagent and free thiols. The obtained hydrogels can be further functionalized with functional moieties (e.g., targeting ligands) for the selective adhesion of cells. This approach is applicable to various natural and synthetic polymers for the assembly of hydrogels with a minimized gelation time, which is promising for various biological applications.

Biologically Derived Nanoarchitectonic Coatings for the Engineering of Hemostatic Needles.

Bleeding after venipuncture could cause blood loss, hematoma, bruising, hemorrhagic shock, and even death. Herein, a hemostatic needle with antibacterial property is developed via coating of biologically derived carboxymethyl chitosan (CMCS) and Cirsium setosum extract (CsE). The rapid transition from films of the coatings to hydrogels under a wet environment provides an opportunity to detach the coatings from needles and subsequently seal the punctured site. The hydrogels do not significantly influence the healing process of the puncture site. After hemostasis, the coatings on hemostatic needles degrade in 72 h without inducing a systemic immune response. The composition of CMCS can inhibit bacteria of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus by destroying the membrane of bacteria. The hemostatic needle with good hemostasis efficacy, antibacterial property, and safety is promising for the prevention of bleeding-associated complications in practical applications.

Vaccination of TLR7/8 Agonist-Conjugated Antigen Nanoparticles for Cancer Immunotherapy.

Nanovaccine-based immunotherapy can initiate strong immune responses and establish a long-term immune memory to prevent tumor invasion and recurrence. Herein, the assembly of redox-responsive antigen nanoparticles (NPs) conjugated with imidazoquinoline-based TLR7/8 agonists for lymph node-targeted immune activation is reported, which can potentiate tumor therapy and prevention. Antigen NPs are assembled via the templating of zeolitic imidazolate framework-8 NPs to cross-link ovalbumin with disulfide bonds, which enables the NPs with redox-responsiveness for improved antigen cross-presentation and dendritic cell activation. The formulated nanovaccines promote the lymphatic co-delivery of antigens and agonists, which can trigger immune responses of cytotoxic T lymphocytes and strong immunological memory. Notably, nanovaccines demonstrate their superiority for tumor prevention owing to the elicited robust antitumor immunity. The reported strategy provides a rational design of nanovaccines for enhanced cancer immunotherapy.

Modular Metal-Quinone Networks with Tunable Architecture and Functionality.

Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones through metal-acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, hydrophilic, and pH-degradable materials. A library of metal-quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to the assembly of particles, tubes, capsules, and films. Importantly, MQNs show bidirectional pH-responsive disassembly in acidic and alkaline solutions, where the quinone ligands mediate the disassembly kinetics, enabling temporal and spatial control over the release of multiple components using multilayered MQNs. Leveraging this tunable release and the inherent medicinal properties of quinones, MQN prodrugs with a high drug loading (>89 wt %) are engineered using doxorubicin for anti-cancer therapy and shikonin for the inhibition of the main protease in the SARS-CoV-2 virus.

Promoting water dissociation for efficient solar driven CO2 electroreduction via improving hydroxyl adsorption.

Exploring efficient electrocatalysts with fundamental understanding of the reaction mechanism is imperative in CO2 electroreduction. However, the impact of sluggish water dissociation as proton source and the surface species in reaction are still unclear. Herein, we report a strategy of promoting protonation in CO2 electroreduction by implementing oxygen vacancy engineering on Bi2O2CO3 over which high Faradaic efficiency of formate (above 90%) and large partial current density (162 mA cm-2) are achieved. Systematic study reveals that the production rate of formate is mainly hampered by water dissociation, while the introduction of oxygen vacancy accelerates water dissociation kinetics by strengthening hydroxyl adsorption and reduces the energetic span of CO2 electroreduction. Moreover, CO3* involved in formate formation as the key surface species is clearly identified by electron spin resonance measurements and designed in situ Raman spectroscopy study combined with isotopic labelling. Coupled with photovoltaic device, the solar to formate energy conversion efficiency reaches as high as 13.3%.

Immune Exosomes Loading Self-Assembled Nanomicelles Traverse the Blood-Brain Barrier for Chemo-immunotherapy against Glioblastoma.

Effective drug delivery and prevention of postoperative recurrence are significant challenges for current glioblastoma (GBM) treatment. Poor drug delivery is mainly due to the presence of the blood-brain barrier (BBB), and postoperative recurrence is primarily due to the resistance of GBM cells to chemotherapeutic drugs and the presence of an immunosuppressive microenvironment. Herein, a biomimetic nanodrug delivery platform based on endogenous exosomes that could efficiently target the brain without targeting modifications and co-deliver pure drug nanomicelles and immune adjuvants for safe and efficient chemo-immunotherapy against GBM is prepared. Inspired by the self-assembly technology of small molecules, tanshinone IIA (TanIIA) and glycyrrhizic acid (GL), which are the inhibitors of signal transducers and activators of transcription 3 from traditional Chinese medicine (TCM), self-assembled to form TanIIA-GL nanomicelles (TGM). Endogenous serum exosomes are selected to coat the pure drug nanomicelles, and the CpG oligonucleotides, agonists of Toll-like receptor 9, are anchored on the exosome membrane to obtain immune exosomes loaded with TCM self-assembled nanomicelles (CpG-EXO/TGM). Our results demonstrate that CpG-EXO/TGM can bind free transferrin in blood, prolong blood circulation, and maintain intact structures when traversing the BBB and targeting GBM cells. In the GBM microenvironment, the strong anti-GBM effect of CpG-EXO/TGM is mainly attributed to two factors: (i) highly efficient uptake by GBM cells and sufficient intracellular release of drugs to induce apoptosis and (ii) stimulation of dendritic cell maturation and induction of tumor-associated macrophages polarization by CpG oligonucleotides to generate anti-GBM immune responses. Further research found that CpG-EXO/TGM can not only produce better efficacy in combination with temozolomide but also prevent a postoperative recurrence.

Sticktight-inspired PEGylation for low-fouling coatings.

Polyethylene glycol (PEG) has been widely used for modifying surfaces to reduce non-specific interactions with biomolecules, microorganisms, and cells. Herein, we report a sticktight-inspired PEGylation strategy to fabricate low-fouling coatings. The influence of PEG molecular architectures on the PEG density and biological adhesion were studied. Notably, an increase in the number of arms resulted in improved surface PEGylation and an improved antifouling ability against the adhesion of proteins, mammalian cells and bacteria. The molecular architecture-dependent PEGylation strategy is an attractive approach for developing advanced low-fouling coatings.

Enhanced Delivery of TLR7/8 Agonists by Metal-Organic Frameworks for Hepatitis B Virus Cure.

Hepatitis B virus (HBV) infection remains a major challenge to global health due to unsatisfactory treatment efficacy, side effects of current therapies, and immune tolerance. Toll-like receptors 7/8 (TLR7/8) agonists have shown great potential in chronic hepatitis B (CHB) cure, but systemic administration often induces severe side effects due to rapid dispersion into the microvasculature. Herein, we encapsulate an imidazoquinoline-based TLR7/8 agonist (IMDQ) into zeolitic imidazolate framework 8 nanoparticles (IMDQ@ZIF-8 NPs) for HBV immunotherapy. Compared with free IMDQ, IMDQ@ZIF-8 NPs efficiently accumulate in the liver and are selectively taken up by antigen-presenting cells (APCs), leading to enhanced APC activation and efficient viral elimination in HBV-infected models. Strikingly, MDQ@ZIF-8 NP treatment results in the obvious production of anti-HBs antibody and seroconversion in HBV-infected mice. Overall, this study on the convergence of a facile assembly approach and efficient therapeutic effects represents a promising strategy for HBV treatment.

Engineering Poly(ethylene glycol) Nanoparticles for Accelerated Blood Clearance Inhibition and Targeted Drug Delivery.

Surface modification with poly(ethylene glycol) (PEGylation) is an effective strategy to improve the colloidal stability of nanoparticles (NPs) and is often used to minimize cellular uptake and clearance of NPs by the immune system. However, PEGylation can also trigger the accelerated blood clearance (ABC) phenomenon, which is known to reduce the circulation time of PEGylated NPs. Herein, we report the engineering of stealth PEG NPs that can avoid the ABC phenomenon and, when modified with hyaluronic acid (HA), show specific cancer cell targeting and drug delivery. PEG NPs cross-linked with disulfide bonds are prepared by using zeolitic imidazolate framework-8 NPs as templates. The reported templating strategy enables the simultaneous removal of the template and formation of PEG NPs under mild conditions (pH 5.5 buffer). Compared to PEGylated liposomes, PEG NPs avoid the secretion of anti-PEG antibodies and the presence of anti-PEG IgM and IgG did not significantly accelerate the blood clearance of PEG NPs, indicating the inhibition of the ABC effect for the PEG NPs. Functionalization of the PEG NPs with HA affords PEG NPs that retain their stealth properties against macrophages, target CD44-expressed cancer cells and, when loaded with the anticancer drug doxorubicin, effectively inhibit tumor growth. The innovation of this study lies in the engineering of PEG NPs that can circumvent the ABC phenomenon and that can be functionalized for the improved and targeted delivery of drugs.

Confined microemulsion sono-polymerization of poly(ethylene glycol) nanoparticles for targeted delivery.

Confined sono-polymerization is developed to prepare poly(ethylene glycol) nanoparticles within water-in-oil microemulsion, followed by post-functionalization with a bispecific antibody (anti HER2 and anti PEG) for targeted delivery of photosensitizers (i.e., indocyanine green). The nanoparticles could specifically target to breast cancer cells (i.e., SKBR3) that overexpress HER2 receptors for the inhibition of cancer cell growth under 808 nm laser irradiation. This study highlights a facile and controllable method to fabricate therapeutic nanoparticles capable of targeted delivery.

Self-reporting of damage in underwater hierarchical ionic skins via cascade reaction-regulated chemiluminescence.

Self-reporting of damage in underwater materials allows on-demand maintenance and, therefore, improves the reliability of materials used in aquatic environments. Here, we report a chemiluminescence-based strategy to self-report the mechanical damage (e.g., fracture or puncture) in underwater hierarchical ionic skins (HI-skins). The chemiluminescence-based self-reporting is regulated by a cascade reaction, which first occurs at the interface between water and the damage location and then spreads through the whole material. When the HI-skins were mechanically damaged underwater, the pre-embedded calcium peroxide became exposed to and reacted with water to generate hydrogen peroxide that further activated the peroxyoxalate chemiluminescence reaction for reporting the damage. The luminescence wavelength could be tuned (439, 508, or 603 nm) and the damage-induced luminescence lasted for up to 12 h. The self-reporting HI-skins also displayed high mechanical and electronic restorability (93% healing efficiency), excellent stretchability (1600%), impressive room-temperature ionic conductivity (1.7 × 10-4 S cm-1), and durable strain sensing performance (highly reproducible electrical response over 1000 uninterrupted strain cycles), making them suitable and reliable candidates for underwater soft ionotronics.

Metal Ion-Directed Functional Metal-Phenolic Materials.

Metal ions are ubiquitous in nature and play significant roles in assembling functional materials in fields spanning chemistry, biology, and materials science. Metal-phenolic materials are assembled from phenolic components in the presence of metal ions through the formation of metal-organic complexes. Alkali, alkali-earth, transition, and noble metal ions as well as metalloids interacting with phenolic building blocks have been widely exploited to generate diverse hybrid materials. Despite extensive studies on the synthesis of metal-phenolic materials, a comprehensive summary of how metal ions guide the assembly of phenolic compounds is lacking. A fundamental understanding of the roles of metal ions in metal-phenolic materials engineering will facilitate the assembly of materials with specific and functional properties. In this review, we focus on the diversity and function of metal ions in metal-phenolic material engineering and emerging applications. Specifically, we discuss the range of underlying interactions, including (i) cation-π, (ii) coordination, (iii) redox, and (iv) dynamic covalent interactions, and highlight the wide range of material properties resulting from these interactions. Applications (e.g., biological, catalytic, and environmental) and perspectives of metal-phenolic materials are also highlighted.