Jilin Tang

Delayed healing of bacterially infected wounds stems from drug‐resistant bacterial invasion and excessive reactive oxygen species (ROS)‐driven inflammation, which necessitating strategies that simultaneously eradicate pathogens and resolve inflammation. We designed a bimetallic CoNi‐based metal–organic framework (CoNi‐MOF) with enhanced multienzyme‐like activities: oxidase‐like (OXD‐like), peroxidase‐like (POD‐like), and catalase‐like (CAT‐like) activities. The superior performance arises from the synergy between Co and Ni, which shifts the d‐band center of Co closer to the Fermi level than those in Co‐MOF and Ni‐MOF. This electronic structure enhancement facilitates substrate adsorption and lowers reaction energy barriers, accounting for the strong enzyme‐like activities of CoNi‐MOF. At acidic infection sites, OXD‐like and POD‐like activities are activated to generate antibacterial ROS, effectively eliminating drug‐resistant bacteria. As bacterial clearance occurs and the wound returns to neutrality, CoNi‐MOF exhibits CAT‐like activity and radical scavenging capabilities to eliminate excess ROS, thereby restoring oxidative balance and mitigating inflammation. Moreover, CoNi‐MOF promotes macrophage polarization from the pro‐inflammatory M1 phenotype toward the pro‐regenerative M2 phenotype. This pH‐responsive enzymatic activity offers a self‐adaptive therapeutic strategy, as validated by in vivo studies showing accelerated wound healing. This self‐adaptive nanozyme platform integrates antibacterial, antioxidant, and immunomodulatory functions, offering a promising antibiotic‐free treatment for drug‐resistant bacterial wound infections.

Persistent bacterial biofilms pose a formidable obstacle to the clinical management of infected wounds, excessive oxidative stress and dysregulated inflammatory responses. Herein, a pH-responsive multifunctional hydrogel (QS@CD-MXCMC) was fabricated by integrating carbon dots (CDs) and CuMn-curcumin metal-polyphenol network loaded MXene (MXCMC) nanosheets into a quaternary ammonium chitosan-sodium alginate (QS) hydrogel matrix. The pH-responsive fluorescence of CDs enables visual indication of wound microenvironmental changes, providing a convenient approach for monitoring wound status. Meanwhile, the MXCMC nanosheets combine the photothermal activity of MXene with the antioxidant activity of the CuMn-curcumin metal-polyphenol network, enabling NIR-triggered bacterial and biofilm elimination while alleviating excessive oxidative stress. Furthermore, the hydrogel modulated the macrophage response by favoring the transition toward the anti-inflammatory M2 phenotype, thereby creating a more conducive microenvironment for tissue repair. In a full-thickness wound model infected with MRSA, QS@CD-MXCMC combined with NIR irradiation markedly decreased the bacterial load and facilitated tissue regeneration, as evidenced by enhanced re-epithelialization, collagen accumulation, and neovascularization. These therapeutic effects ultimately resulted in accelerated wound closure. By integrating visual indication with antibacterial and microenvironment-regulating functions in a single hydrogel, QS@CD-MXCMC provides an integrated strategy for infected wound management.

TROP2 has emerged as a significant biomarker and therapeutic target in various epithelial cancers, owing to its tissue-specific expression and its association with tumor proliferation, invasion, and metastasis. Tumor cell migration is a critical determinant of tumor invasiveness and malignancy, serving as a pivotal factor in prognosis assessment and therapeutic response evaluation. Despite these insights, the molecular mechanisms underpinning TROP2's role in tumor progression─particularly in mediating tumor cell migration─remain incompletely understood. Desmosomes, as essential cell-cell adhesion structures, are integral to maintaining tissue architecture; however, how subtle alterations in their expression and structural organization influence tumor cell adhesion warrants further investigation. In this study, we employed direct stochastic optical reconstruction microscopy (dSTORM) coupled with biochemical approaches to elucidate the mechanism by which TROP2 regulates tumor cell migration via desmosomal cadherin DSG2. Co-localization imaging and coimmunoprecipitation assays confirmed an interaction between TROP2 and DSG2. By establishing TROP2 overexpression and knockdown cell lines, we observed that high TROP2 expression not only downregulated DSG2 levels but also impaired desmosome assembly. These findings were further confirmed at the tissue level. Moreover, we found that TROP2 facilitated tumor cell proliferation and migration by suppressing DSG2 expression and activating EGFR/AKT and FAK downstream signaling pathways. Our findings reveal the molecular mechanism by which TROP2 promotes migration, highlighting the critical role of intercellular junction integrity in cancer progression. These insights provide a foundation for developing targeted therapies against TROP2 and its associated signaling mechanisms in epithelial malignancies.

Tooth whitening has attracted considerable attention as it can enhance appearance and improve oral health. Nanocatalysts with peroxidase-like activity can catalyze H₂O₂ to generate reactive oxygen species (ROS), a process known as chemodynamic therapy (CDT). The ROS generation can achieve effective tooth whitening and caries prevention. Nonetheless, traditional CDT methods often struggle with controlling the reaction process by adjusting the concentrations of H₂O₂ or nanocatalysts. An excessive ROS can harm oral tissues, whereas insufficient ROS may compromise therapeutic efficacy. To address this issue, this study designed a hydrogel bilayer that separately encapsulates H₂O₂ and iron-based metal-organic frameworks (Fe-MOFs) nanoparticles (NPs) with peroxidase-like activity. The ROS generation was regulated by leveraging the concentration-gradient diffusion of H₂O₂. Through Monte Carlo simulations and machine learning algorithms, mathematical formulas were derived to elucidate how to harness concentration-gradient diffusion for near-independent modulation of the reaction half-life and rate. The experimental results demonstrated that being guided by the formulas could effectively avoid the initial burst of ROS and manipulate the ROS generation duration, thereby achieving safe and effective tooth whitening and caries prevention. We anticipate that this bilayer design strategy can be extended to other CDT systems, enabling precise control over therapeutic outcomes.

The treatment of persistent drug‐resistant bacterial infections in wounds poses a significant global medical challenge. Developing innovative antimicrobial strategies capable of simultaneously achieving bacterial eradication, inflammation resolution, and tissue regeneration has become imperative. Herein, a nanocomposite featuring plasma‐enhanced enzymatic activity and immunoregulatory properties is engineered, designed to reprogram the wound microenvironment and expedite healing in drug‐resistant bacterial infections. Capitalizing on the localized surface plasmon resonance effect of Au@Ag nanoparticles coupled with the pH‐dependent peroxidase‐like (POD‐like) activity of cerium dioxide (CeO ₂ ), the BSA‐(Au@Ag/CeO ₂ ) nanocomposites orchestrate dual‐modality photothermal‐chemodynamic therapy for enhanced bactericidal efficacy and biofilm disruption. Upon near‐infrared laser irradiation, plasmon‐generated hot electrons are transferred to CeO ₂ , triggering massive reactive oxygen species production via enhanced POD‐like catalysis. This synergistic dual‐action mechanism eradicates methicillin‐resistant Staphylococcus aureus (MRSA) through membrane disruption and reactive oxygen species (ROS)‐induced oxidative stress. Remarkably, the nanosystem not only suppresses proinflammatory cytokine storms but also steers macrophage polarization toward tissue reparative M2 phenotypes at infection sites, thereby alleviating pathological inflammation and fostering regenerative microenvironments. Biosafety assessments confirm the absence of discernible toxicity in vital organs. This multifunctional platform represents a paradigm‐shifting strategy for managing antibiotic‐resistant wound infections, providing a clinically translatable solution to combat antimicrobial resistance.

Treating androgenetic alopecia (AGA) with platelet-rich plasma (PRP) holds great promise; however, effective and comfortable delivery remains a challenge. Direct injection causes pain, and PRP-incorporated microneedles (MNs) have low hardness and slow dissolution. To tackle this problem, we propose a machine-learning (ML)-driven strategy, which involves integrating the selection of therapeutic substances, orthogonal experiment designs, ML prediction, and Pareto front identification. Through the implementation of only 18 experiments based on orthogonal experiment designs, this ML-assisted strategy can pinpoint an optimal material composition that concurrently attains high hardness and rapid dissolution. We utilized this optimal material composition to fabricate MNs, and their biological functionality was demonstrated through multiple aspects, including the sustained release of various growth factors over 30 days, more than 90% bacterial inhibition, reactive oxygen species scavenging, and the promotion of the proliferation of dihydrotestosterone-damaged human dermal papilla cells. In vivo studies indicated significant hair regrowth in AGA mice through the activation of the Wnt/β-catenin pathway, outperforming the effects of minoxidil. Significantly, this approach eliminates the biosafety risks associated with the use of synthetic materials. The developed framework is anticipated to serve as a generalizable paradigm for expediting the clinical translation of biomaterials such as MNs.

The mechanical properties of nanocarriers and the ability of tumor cells to sense mechanical cues are critical factors in regulating cellular internalization. During epithelial-mesenchymal transition (EMT), tumor cells undergo changes that enhance their invasiveness, but how these changes affect their ability to sense mechanical cues, thereby impacting drug delivery efficiency and treatment effects, is still unknown. Here, we synthesized chitosan nanoparticles (CSNPs) with different Young's moduli ranging from 0.325 to 18.25 MPa. Our findings revealed that as EMT progresses, tumor cells exhibited enhanced internalization capacity, attributing to the elevated integrin expression by EMT. During the cellular internalization of CSNPs with different Young's moduli, the stiffer CSNPs displayed more internalization in tumor cells. It was due to the upregulation of p-FAK expression after the integrin of cells sensed stronger mechanical cues generated by stiffer CSNPs, resulting in promoted F-actin polymerization, ultimately achieving more cellular internalization. After loading doxorubicin (DOX) into CSNPs (DOX-CSNPs), the stiffer DOX-CSNPs exhibited higher inhibitory ability, with mesenchymal phenotype tumor cells displaying the highest treatment effect. Taken together, our work demonstrated how the mechanical properties of nanocarriers affect cellular internalization across different EMT stages and provided a mechanical-based nanocarrier engineering strategy for cells undergoing EMT.

Chronic wounds infected with drug‐resistant bacteria present a formidable clinical challenge, exacerbated by antibiotic overuse that severely compromises healing. Herein, a multifunctional therapeutic hydrogel wound dressing is developed to address these challenges. This advanced nanocomposite hydrogel incorporates cerium dioxide‐doped MXene nanosheets (MXene@CeO ₂ ) within a glycidyl methacrylate‐modified gelatin (GMA‐Gelatin) matrix and crosslinked into a hydrogel under UV irradiation (GMAG‐GEL), forming a near‐infrared (NIR)‐responsive material (MXene@CeO ₂ /GMAG‐GEL). This incorporation enhances the mechanical strength of the hydrogel and creates a protective microenvironment for wound repair. In the acidic environment of bacterial infections, MXene@CeO ₂ /GMAG‐GEL facilitates the electrostatic capture of bacteria. Synergizing with its photothermal capability, it exhibits exceptional antibacterial activity, effectively killing drug‐resistant bacteria and disrupting bacterial biofilms. After eradicating the infection, MXene@CeO ₂ /GMAG‐GEL further alleviates oxidative stress, promotes cell migration and angiogenesis, and induces macrophage polarization toward an anti‐inflammatory phenotype. In vivo studies confirmed MXene@CeO ₂ /GMAG‐GEL significantly accelerates wound closure and tissue regeneration. This work overcomes the key challenges of antibiotic resistance, persistent inflammation, and impaired tissue regeneration, presents a comprehensive therapeutic strategy for drug‐resistant bacterial wound infections through a single multifunctional platform.