Articular fibrocartilage-targeted therapy by microtubule stabilization.

The fibrocartilage presented on the joint surface was caused by cartilage injury or degeneration. There is still a lack of effective strategies for fibrocartilage. Here, we hypothesized that the fibrocartilage could be viewed as a raw material for the renewal of hyaline cartilage and proposed a previously unidentified strategy of cartilage regeneration, namely, "fibrocartilage hyalinization." Cytoskeleton remodeling plays a vital role in modifying the cellular phenotype. We identified that microtubule stabilization by docetaxel repressed cartilage fibrosis and increased the hyaline cartilage extracellular matrix. We further designed a fibrocartilage-targeted negatively charged thermosensitive hydrogel for the sustained delivery of docetaxel, which promoted fibrocartilage hyalinization in the cartilage defect model. Moreover, the mechanism of fibrocartilage hyalinization by microtubule stabilization was verified as the inhibition of Sparc (secreted protein acidic and rich in cysteine). Together, our study suggested that articular fibrocartilage-targeted therapy in situ was a promising strategy for hyaline cartilage repair.

A Valence-Engineered Self-Cascading Antioxidant Nanozyme for the Therapy of Inflammatory Bowel Disease.

Antioxidant treatment strategy by scavenging reactive oxygen species (ROS) is a highly effective disease treatment option. Nanozymes with multiple antioxidant activities can cope with the diverse ROS environment. However, lack of design strategies and limitation of negative correlation for nanozymes with multiple antioxidant activities hindered their development. To overcome these difficulties, here we used ZnMn2 O4 as a model to explore the role of Mn valency at the octahedral site via a valence-engineered strategy, and found that its multiple antioxidant activities are positively correlated with the content of Mn4+ . Therefore, through this strategy, a self-cascading antioxidant nanozyme LiMn2 O4 was constructed, and its efficacy was verified at the cellular level and in an inflammatory bowel disease model. This work not only provides guidance for the design of multiple antioxidant nanozymes, but also broadens the biomedical application potential of multiple antioxidant nanozymes.

Multifunctional Nanozyme Hydrogel with Mucosal Healing Activity for Single-Dose Ulcerative Colitis Therapy.

Nanozymes are nanomaterials with enzyme-like activities, which have been developed for inflammatory disease therapy by reactive oxygen species (ROS) scavenging. The application of nanozymes in ulcerative colitis (UC) treatment not only inherits the merits of small molecular antioxidants (e.g., 5-aminosalicylic acid) to scavenge ROS but also achieves catalytic recycle instead of stoichiometric consumption. However, current therapies usually ignore the repair of mucosa, the first line of defense, whose damage increases the risk of infections. Herein, a multifunctional nanozyme hydrogel is designed and verified both as an ROS scavenger and a mucosal healing enhancer for UC therapy. The chitosan-coated CeO2 nanozyme (CCNZ) not only possesses excellent ROS-scavenging ability but also exhibits satisfactory antibacterial capacity. After gelation with alginate, the optimized CCNZ1:Alg1.5 nanozyme hydrogel exhibits multiple functions, including inflamed site targeting, supporting cell growth, ROS scavenging, and antibacterial activity, which alleviates UC better than a clinical medication 5-aminosalicylic acid by even a single-dose treatment. This study reveals that a nanozyme providing mucosal healing is promising for UC therapy with excellent potential for clinical application and enriches the nanozyme research of treatment for diseases.

Ligand-Dependent Activity Engineering of Glutathione Peroxidase-Mimicking MIL-47(V) Metal-Organic Framework Nanozyme for Therapy.

Glutathione peroxidase (GPx) plays an important role in maintaining the reactive oxygen metabolic balance, yet limited GPx-mimicking nanozymes are currently available for in vivo therapy. Herein, a ligand engineering strategy is developed to modulate the GPx-mimicking activity of a metal-organic framework (MOF) nanozyme. With different substituted ligands, the GPx-mimicking activities of MIL-47(V)-X (MIL stands for Materials of Institute Lavoisier; X=F, Br, NH2 , CH3 , OH, and H) MOFs are rationally regulated. With the best one as an example, both in vitro and in vivo experiments reveal the excellent antioxidation ability of MIL-47(V)-NH2 , which alleviates the inflammatory response effectively for both ear injury and colitis, and is more active than MIL-47(V). This study proves that high-performance GPx-mimicking nanozymes can be rationally designed by a ligand engineering strategy, and that structure-activity relationships can direct the in vivo therapy. This study enriches nanozyme research and expands the range of biomimetic MOFs.

Solar-driven plasmonic heterostructure Ti/TiO2-x with gradient doping for sustainable plasmon-enhanced catalysis.

Plasmon-enhanced harvesting of photons has contributed to the photochemical conversion and storage of solar energy. However, high dependence on noble metals and weak coupling in heterostructures constrain the progress towards sustainable plasmonic enhancement. Here earth-abundant Ti is studied to achieve the plasmonic enhancement of catalytic activity in a solar-driven heterostructure Ti/TiO2-x. The heterostructure was fabricated by engineering an intense coupling of a surface-etched Ti metal and a gradient-based TiO2-x dielectric via diffusion doping. Ti/TiO2-x exhibits a highly resonant light absorption band associated with surface plasmon resonances that exhibit strong near-field enhancement (NFE) and hot electron injection effects. In a photoelectrochemical system, intense interaction of the resonant plasmons with a vicinal TiO2-x dielectric accelerates the transfer of solar energy to charge carriers for plasmon-enhanced water splitting reactions. Moreover, the plasmonic Ti/TiO2-x structure presents sustained enhanced redox activities over 100 h. The intense coupling by gradient doping offers an effective approach to enable the plasmon resonances of Ti excited by visible light. The Ti-based plasmonic heterostructure potentially opens an alternative avenue towards sustainable plasmon-enhanced catalysis.

Importance of zwitterionic incorporation into polymethacrylate-based hydrogels for simultaneously improving optical transparency, oxygen permeability, and antifouling properties.

Conventional 2-hydroxyethyl methacrylate (HEMA)-based hydrogels have an inverse relationship between optical transparency (OP) and oxygen permeability (Dk) as a function of water content. While the higher water content favors the oxygen permeability of HEMA-based hydrogels, it also causes poor optical transparency due to the water-induced scattering center effect. Here, we propose and demonstrate that the incorporation of zwitterionic [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA) with HEMA hydrogels enables the achievement of both properties (OP = 98% and Dk = 54.7) in hydrogels at high water contents of 84%, and both values are much higher than those of pure HEMA hydrogels (OP = 2.3% and Dk = 17.5 barriers). HEMA-SBMA hydrogels are crosslinked by electrostatic interactions between the zwitterionic SBMA groups and hydrogen bonds between the HEMA groups. The introduction of SBMA into HEMA not only increases the quantity and quality of strongly binding water inside the networks, but also affects the porous structure of the gels, both of which are correlated with OP and Dk. Moreover, hybrid HEMA-SBMA hydrogels demonstrate their excellent antifouling function to prevent nonspecific protein adsorption in vitro, as well as their biocompatibility and hemocompatibility when implanted in mice in vivo. A combination of these excellent properties of HEMA-SBMA hydrogels (high water content, high optical transparency, high oxygen permeability, good antifouling function, and low foreign-body reaction) makes them highly promising for contact lens-based ophthalmic applications. This work, in line with our other HEMA-CBMA hydrogels, offers a new strategy to design hybrid hydrophilic-zwitterionic materials for improving their multi-faceted properties of interest, beyond the conventional designs of hydrophilic-hydrophilic and hydrophilic-hydrophobic materials.