Drug-resistant bacterial infections in chronic wounds remain a critical challenge, particularly under persistent inflammation. Here, we report the de novo design of high-entropy alloy (HEA, PtFeCuCoNi)-based Janus artificial enzymes with pH-gated redox biocatalysis for sequential antibacterial and repair functions. The multi-metal synergy stabilizes the d-band center, allowing acidic oxidase/peroxidase-like activity and neutral antioxidase-like activity. In infection, the enzymes generate bactericidal reactive oxygen species (ROS) to eliminate methicillin-resistant Staphylococcus aureus (MRSA) and biofilms at ultralow concentrations (8 μg/mL). During healing, they scavenge ROS, alleviate oxidative injury and support cellular proliferation. In MRSA-infected wounds, this dual-action system clears bacteria and then accelerates regeneration through enhanced neovascularization and matrix remodeling. Mechanistic analyses reveal PFKFB3-mediated metabolic reprogramming, suppression of pro-inflammatory cytokines, and macrophage polarization toward the M2 phenotype. Integrating pH-gated antimicrobial and immunomodulatory repair within one nanoplatform, this strategy addresses the conflicting demands of infection control and tissue healing.

Accurate quantification of drug concentration within the skin's interstitial fluid (ISF) remains a significant analytical challenge due to the limitations of invasive sampling and the inability of bulk measurements to resolve micro-scale distribution. Traditionally, predictive models have treated the skin as a static barrier, ignoring the dynamic matrix effects caused by ISF flow, which leads to substantial errors in estimating deep-tissue analyte concentrations. To address this, this study proposes a computational analytical strategy integrating Finite Element Method (FEM) with Computational Fluid Dynamics (CFD) to quantitatively profile drug transport under varying thermal conditions. By calibrating against HPLC-validated ex vivo permeation data at a reference temperature, diffusion coefficients and ISF flow velocities were extrapolated to predict behavior at other temperatures. This approach effectively decouples the influence of fluid dynamics from passive diffusion, allowing for the precise resolution of temperature-dependent permeation kinetics. The Flow-Field model demonstrated strong correlations with ex vivo skin permeation tests, achieving R2 values over 0.99 for various drugs and temperature conditions. This work establishes a robust in silico tool for the micro-scale profiling of analytes in complex biological tissues, offering a non-invasive alternative to estimate ISF concentrations where physical sampling is restricted.

Ferroptosis, a newly recognized form of regulated cell death, has emerged as a promising strategy in cancer therapy. Given the high incidence and recurrence rates of bladder cancer, exploring novel therapeutic approaches is critically important. In this study, we developed a novel intravesical nanoplatform, FBZ@BSA@PDA, that integrates ferroptosis-related oxidative injury immunogenic cell death (ICD) activation, and photothermal therapy (PTT) to achieve synergistic treatment of bladder cancer. The hydrophobic drug fenbendazole (FBZ) was efficiently encapsulated via thermally induced unfolding of bovine serum albumin (BSA), and polydopamine (PDA) was formed by in situ polymerization of dopamine to enhance tissue adhesion and photothermal responsiveness. Following transurethral intravesical administration, the platform enabled sustained drug release and localized PTT. Mechanistically, it induced lipid peroxidation (LPO), GSH depletion, and mitochondrial dysfunction, which suggest that ferroptosis may contribute to tumor cell death. This was accompanied by key ICD markers, including calreticulin (CRT) exposure, high mobility group box 1 (HMGB1) release, and adenosine triphosphate (ATP) secretion, which effectively promoted dendritic cell (DC) maturation and T-cell activation. FBZ@BSA@PDA demonstrated strong anti-tumor efficacy and favorable biosafety in an orthotopic mouse model of bladder cancer. This strategy offers a promising localized immune-potentiated therapeutic approach for clinical bladder cancer treatment.

MXene/biomacromolecule composites have rapidly emerged as a versatile class of hybrids that couple the electrical and photothermal functionalities of MXenes with the mechanical reinforcement and bio-derived processability of natural macromolecules. This review establishes a unified framework for the field by classifying the architectures reported into four representative categories, namely membranes or films, papers, gels, and nonwoven structures, and by systematically comparing their fabrication strategies, including vacuum-assisted assembly, solution casting, printing, electrospinning, and gelation. The interfacial assembly principles governing structure formation and property retention are summarized, with an emphasis on interfacial hydrogen bonding, electrostatic and coordination interactions, together with hierarchical structural confinement that suppresses MXene restacking and enables continuous transport pathways. Recent progress is critically compared across electromagnetic interference shielding, soft actuation, biomedicine, energy storage, flexible electronic devices, and water purification, highlighting structures, properties, application correlations and performance-limiting factors. Key challenges and opportunities are identified, including oxidation mitigation and long-term stability, scalable manufacturing and large-area processing, standardized biosafety evaluation, and multifunctional integration guided by computations and machine learning. This review provides design principles and practical considerations to accelerate the rational development of robust and sustainable MXene/biomacromolecule composites.

The cGAS-STING pathway serves as a central hub for DNA-triggered innate immune activation in tumors. Nevertheless, the clinical translation of stimulator of interferon genes (STING) agonists remains hindered by challenges such as rapid in vivo degradation, inefficient cytosolic delivery, and the risk of systemic inflammation. Inorganic nanomaterials, leveraging their high specific surface area, tunable size and morphology, and unique surface chemical properties, provide an ideal platform for the precise delivery and spatiotemporally controlled release of STING agonists. Furthermore, these materials can induce the release of double-stranded DNA (dsDNA) to activate STING while also synergistically potentiating STING activation through the induction of immunogenic cell death or the release of specific metal ions. This review highlights that the application of inorganic nanomaterials in STING pathway activation extends beyond simple agonist delivery to encompass precise spatiotemporal control and modulation of signal intensity. We systematically outline design strategies for inorganic platforms that facilitate agonist protection and stimuli-responsive release. Furthermore, we discuss their synergistic integration with therapeutic modalities, including radiosensitization, reactive oxygen species (ROS) induced DNA damage, and immunogenic cell death (e.g., pyroptosis and ferroptosis), ultimately contributing to the establishment of a cGAS-STING amplification immune circuit. By achieving synergistic integration of delivery, activation, and potentiation, inorganic nanomaterials enhance both the efficacy and safety of STING-targeted immunotherapy, realizing the integrated functional advantage of "carrier-adjuvant-inducer" and offering a new paradigm for cancer immunotherapy.

Efficient CH4 capture from low-concentration coal mine gas is of great significance. Metal–organic frameworks (MOFs) are promising adsorbents owing to their high porosity and structural tunability. Nevertheless, regulating the relationship between the MOFs structure and CH4 capture performance, as well as developing rational strategies to overcome the adsorption bottleneck of MOFs, remain critical challenges. Herein, we present the first systematic study on the effect of pore environment and adsorption sites on CH4 capture, employing archetypical MOFs incorporating diverse metal centers (Zr, Zn, Fe, Co, and Cu). Interestingly, HKUST-1(Cu), with a matched pore size and open-metal sites, exhibited the highest adsorption capacity. Furthermore, by leveraging polyvinylpyrrolidone(PVP)-assisted pore modulation, HKUST-1-Px exhibited concentration-dependent growth. At low PVP concentrations, it selectively modulates the growth kinetics of crystallographic facets through coordination and steric effects, whereas at high concentrations, excessive PVP preferentially forms a dense layer that stabilizes the crystal dimensions and promotes isotropic growth. Moreover, the CH4 adsorption capacity of HKUST-1-Pₓ follows an intriguing volcano-type trend with varying PVP content. Notably, HKUST-1-P0.4 affords the best adsorption performance—30% higher than that of HKUST-1. Grand Canonical Monte Carlo simulations reveal that the coordination between PVP and Cu nodes tactfully reconstructs the pore distribution of HKUST-1-Px and strengthens CH4 binding, as evidenced by the decrease in the adsorption energy of the CH4 molecule from -18.05 kJ/mol (HKUST-1) to -27.15 kJ/mol (HKUST-1-P0.4). This study provides experimental and theoretical insights to clarify the MOF structure–property relationships involved in CH4 capture, as well as innovative polymer-induced strategies for designing high-performance CH4-capture adsorbents for low-concentration coal mine gas.

Cancer immunotherapy has revolutionized oncology by harnessing the host immune system to eliminate malignant cells; however, its clinical efficacy remains limited in many solid tumors due to insufficient immune activation, poor intratumoral delivery, and an immunosuppressive tumor microenvironment (TME). Recently, inorganic nanoparticle–bacteria biohybrids have emerged as a promising strategy to overcome these challenges by integrating the intrinsic tumor-targeting and immune-stimulating properties of bacteria with the programmable physicochemical and therapeutic functions of inorganic nanoparticles (INPs). In these biohybrid systems, bacteria serve as active carriers that selectively colonize tumors and initiate immune responses, while INPs enable controllable therapeutic activation through catalytic therapy, phototherapy, and immune modulation. This synergistic integration facilitates localized therapeutic action, enhances immunogenic cell death, promotes antigen presentation, and amplifies antitumor immune responses. In this review, we systematically summarized recent advances in INP-bacteria biohybrids for cancer immunotherapy, focusing on their design and fabrication strategies, immune-enhancing mechanisms, and applications in combination therapies. Furthermore, current challenges, including biosafety, structural stability, and clinical translation, are discussed, and future perspectives for developing next-generation biohybrid immunotherapeutic platforms are highlighted. This review provides a comprehensive framework for the rational design and clinical development of INP–bacteria biohybrids for enhanced cancer immunotherapy.

Molybdenum enzymes and one of their catalytic products, uric acid (UA), play important roles in T-cell activation; thereby, enhancing molybdenum enzyme activity and increasing UA levels within tumors can further activate T-cell and enhance anti-tumor immunotherapy. To achieve this goal, biodegradable molybdenum sulfide nanoparticles (MoSX NPs) were synthesized to increase molybdenum enzyme activity and thus effectively potentiate anti-tumor immunity by integrating molybdenum-based metalloimmunotherapy with hydrogen sulfide (H2S) gas therapy. This dual-modality approach not only amplified immune activation but also triggered the stimulator of interferon genes (STING) signaling pathway and modulated purine metabolic networks, thereby orchestrating a comprehensive enhancement of anti-tumor immune responses. In detail, the biodegradable MoSX NPs exhibited excellent GSH-responsiveness, triggering the rapid release of H2S and molybdate ions (MoO4 2-). H2S-mediated mitochondrial damage elicited the release of mitochondrial DNA (mtDNA), which activated the STING pathway, while MoO4 2- further enhanced the activation of the cGAS-STING signaling pathway. As the catalytic moiety of molybdenum, MoO4 2- regulated cellular purine metabolic reprogramming and increased UA level with the tumor, thereby achieving synergistic anti-tumor immune responses. This study proposes a molybdenum-based nanocatalytic strategy to improve purine metabolic networks, activate T-cell, and trigger a strong anti-tumor response, thereby achieving precision metabolic-immune therapy for tumors.

Glioblastoma (GBM) exhibits profound therapeutic resistance and aggressive recurrence, driven not solely by tumor-intrinsic mutations, but by a highly integrated, dynamically evolving tumor microenvironment (TME). In this review, we propose the “GBM Spider Web” model to conceptualize the multidimensional and spatiotemporal crosstalk among immune cells, neurons, glial cells, and the extracellular matrix. We systematically deconstruct this ecosystem, highlighting emerging biological paradigms such as neuron-glioma synaptic communication, astrocyte-mediated mitochondrial transfer, and mechanometabolic reprogramming orchestrated by severe hypoxia and lactate accumulation. Crucially, we elucidate how these diverse microenvironmental stressors converge upon a central signaling nexus, primarily integrating the nuclear factor-κB (NF-κB), Wnt/β-catenin, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathways to drive adaptive evolution, immune evasion, and macroscopic functional syncytium. Furthermore, we comprehensively evaluate next-generation therapeutic strategies designed to disrupt this robust network, ranging from advanced immunotherapies and nanotechnology-based interventions to adaptive physical therapies and the novel targeting of meningeal lymphatic drainage. By shifting the paradigm from isolated tumor-centric pathways to a systemic, network-based perspective, this review provides a strategic framework for overcoming adaptive resistance and guiding the rational design of combinatorial therapies for GBM.

Gouty arthritis faces multiple challenges, such as recalcitrance to cure and recurrent flares, owing to its intricate pathophysiological microenvironment. Recent studies have focused on urate reduction, pain relief, or anti-inflammation effects alone, which often fail to provide satisfactory results. To address these challenges, an implantable manganese platinum microscale galvanic cell (Mn@Pt micro-GC) is developed. This system utilizes the urate oxidase-like activity of platinum to degrade deposited monosodium urate crystals, while the Mn2+ and hydrogen gas work synergistically to effectively reversing the pro-inflammatory environment. In addition to decreasing the production of pain signals associated with gout, Mn@Pt micro-GC effectively inhibits pain signal transmission along the CXCL5-neuronal CXCR2-TRPA1 axis through continuous electrical stimulation. This multimodal treatment approach emphasizes the strong relationship between bone and nerve in gout, taking into account the importance of reducing uric acid, anti-inflammation, and pain relief in gout therapy, which has led to improved treatment results.

Efficient CH4 capture from low-concentration coal mine gas is of great significance. Metal–organic frameworks (MOFs) are promising adsorbents owing to high porosity and structural tunability. Nevertheless, regulating the relationship between the MOFs structure and CH4 capture performance, as well as developing rational strategies to overcome the adsorption bottleneck of MOFs, remain critical challenges. Herein, we present a systematic investigation of pore environments and adsorption sites on CH4 capture, employing representative MOFs with diverse metal centers (Zr, Zn, Fe, Co, and Cu) and different topological structures. Interestingly, HKUST-1(Cu), with a matched pore size and open-metal sites, exhibited the highest adsorption capacity. Furthermore, by leveraging polyvinylpyrrolidone(PVP)-assisted pore modulation, HKUST-1-Px exhibited concentration-dependent growth. At low PVP concentrations, it selectively modulates the growth kinetics of crystallographic facets through coordination and steric effects, whereas at high concentrations, excessive PVP preferentially forms a dense layer that stabilizes the crystal dimensions and promotes isotropic growth. Moreover, the CH4 adsorption capacity of HKUST-1-Pₓ follows an intriguing volcano-type trend with varying PVP content. Notably, HKUST-1-P0.4 affords the best adsorption performance—30% higher than HKUST-1. Grand Canonical Monte Carlo simulations reveal that the coordination between PVP and Cu nodes reconstructs the pore distribution of HKUST-1-Px and strengthens CH4 binding, as evidenced by the decrease in the adsorption energy of the CH4 molecule from −18.05 kJ/mol (HKUST-1) to −27.15 kJ/mol (HKUST-1-P0.4). Finally, the cyclic and breakthrough tests further validated the application potential of HKUST-1-P0.4. This study provides innovative polymer-induced strategies for designing high-performance CH4-capture adsorbents for low-concentration coal mine gas.

Intracerebral hemorrhage (ICH) leads to long-term dysfunction through white matter injury (WMI), characterized by neuroinflammation-driven oligodendrocyte damage and demyelination. Here, we report a synergistic nanotherapy that uses ultra-small CeO2 nanoparticles and is both a potent reactive oxygen species (ROS) scavenger and an efficient carrier for fingolimod (FTY 720). CeO2-FTY 720 effectively reduces ROS, modulates microglial polarization, and promotes oligodendrocyte precursor cell (OPC) proliferation and differentiation in vitro. In an ICH mouse model, it attenuates mitochondrial dysfunction, neuroinflammation, and blood-brain barrier disruption while facilitating WMI repair via OPC proliferation and differentiation. With respect to long-term outcomes, CeO2-FTY 720 remarkably improves spatial learning and sensorimotor functions following ICH. Further study reveals that CeO2-FTY 720 promotes WMI repair after ICH via the STAT3 signaling pathway. Therefore, this study highlights the use of CeO2 to enhance the therapeutic efficacy of FTY 720 and offers a promising approach for the comprehensive treatment of ICH.

Activation of unfolded protein response (UPR) has recently been identified as a new target for cancer therapy. However, pharmacological agents activating UPR have not been approved in clinical practice. In this study, spatiotemporally controllable UPR activation was realized by the combination of ultrasound (US)-triggered sonodynamic therapy (SDT) with titanium nitride (TiN) NPs and proteasome inhibitor bortezomib (BTZ). BTZ-conjugated TiN NPs were prepared by using a linker of carminic acid (CA)-functionalized bovine serum albumin (BSA). CA interacts with BTZ to form dynamic boronate ester bond enabling pH- and ultrasound-responsive drug release and thus overcoming the challenge of poor drug release for the conventional delivery systems. Compared with traditional sonosensitizer TiO2, TiN has superior SDT efficiency. TiN-mediated SDT inhibits not only the β1/β5 active sites of proteasomes, but also the β2 proteasome activity not targeted by BTZ, thus synergistically triggering endoplasmic reticulum (ER) stress. Moreover, SDT and BTZ complement each other perfectly to activate all three pro-apoptotic UPR pathways including PERK/eIF2α/ATF4, IRE1/JNK and ATF6, thereby leading to dramatic upregulation of CHOP expression, calcium overload and mitochondrial dysfunction. Importantly, this intensified ER stress effectively triggers immunogenic cell death (ICD), characterized by the massive release of damage-associated molecular patterns (DAMPs), thereby further recruiting and activating cytotoxic T lymphocytes and reshaping the immunosuppressive tumor microenvironment. In summary, making up the current lack of effective pharmacological agents activating UPR, this study provides a new strategy to spatiotemporally activate UPR through the ingenious combination of SDT and proteasome inhibition with BTZ-conjugated TiN NPs.

Reactive oxygen species (ROS)-based nanomedicine holds great promise for combating biofilm-associated infections (BAIs). Nonetheless, the strong antioxidant systems in these microenvironments lessen the effectiveness of ROS. The combination of ROS generation and depletion of antioxidant pathways is a potential approach to this issue. Herein, we present COF/HKUST-10, a composite platform of a copper-based metal-organic framework (HKUST-1) and pillararene-embedded covalent organic frameworks for BAIs. Both endogenous hydrogen sulfide and exogenous light activate this platform, thereby inducing synergistic catalytic reactions that enhance ROS generation and local antioxidant inhibition. Transcriptomic analysis revealed that ROS and Cu+/Cu2+ overload disrupted porphyrin metabolism in Porphyromonas gingivalis, severely impairing its energy metabolism and pathogenicity. This synergistic "three-in-one" antibacterial strategy involves ROS amplification, antioxidant system depletion, and copper ion-mediated bactericidal effects. The experiments demonstrated the material's exceptional efficacy, resulting in robust antibacterial activity, efficient biofilm eradication, and significant reduction in inflammation. This study presents a distinctive strategy to enable synergistic treatment of BAIs, broadening the practical applications of supramolecular materials in biomedical applications.

Gas therapy, an emerging and promising tumor treatment strategy, has garnered increasing research interest. Recent attention has focused on gas signaling molecules due to their unique biological effects and potent immunomodulatory activities. With rapid advances in nanotechnology, diverse gas-generating nanoplatforms have been developed to augment cancer immunotherapy. This review first elucidates the mechanisms by which bioactive gas molecules amplify anti-tumor immunity and outlines design strategies for constructing gasgenerating nanoplatforms. Thereafter, we summarize the applications of these nanoplatforms in gas-enhanced tumor immunotherapy, highlighting key bioactive gas signal molecules, including hydrogen sulfide (H2S), nitric oxide (NO), carbon monoxide (CO), and hydrogen (H2). Finally, the biosafety profiles of these systems and the prospects for future opportunities and challenges are discussed.

With the advancement of nanomedicine, layered double hydroxides (LDHs) have been extensively investigated for disease treatment due to their exceptional physicochemical properties. Given their significance in tumor therapy and the rapid progress in this class of materials, this review comprehensively summarized their applications in cancer treatment. We began by outlining and illustrating the key features of LDHs, including their tunable composition, controllable biocompatibility, and distinctive physicochemical characteristics. Next, we discussed their role as drug delivery vehicles in passive or active tumor-targeting strategies. Subsequently, we systematically reviewed LDH-based catalytic therapy and immunotherapy, focusing on cases where LDH-based nanocomposites either served as functional components or exerted their intrinsic effects. Notably, we placed particular emphasis on the properties of LDHs themselves, including their structural optimization and ion-dependent functions, which are essential for the rational design of effective LDH-based nanoplatforms for tumor therapy. Finally, based on the current state of the field, we provided insights into the challenges and future prospects of LDHs in clinical or preclinical translations.

Transarterial embolization (TAE) efficacy in hepatocellular carcinoma (HCC) is limited by post-embolization hypoxia-driven angiogenesis and metabolic reprogramming. To address this, we develop pH-responsive gelatin microspheres (GMs) encapsulating zinc sulfide (ZnS) nanoparticles (ZnS-encapsulated gelatin microspheres [ZnS@GMs]) for the dual delivery of hydrogen sulfide (H2S) gas and Zn2+ ions. ZnS@GMs inhibit tumor growth through suppression of the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) axis and glycolytic metabolism, alongside promoting vascular normalization and immune activation. Mechanistically, H2S disrupts mitochondrial respiration, increasing oxygen levels and destabilizing HIF-1α, whereas Zn2+ inhibits hexokinase and lactate dehydrogenase, depleting ATP and biosynthetic intermediates. Furthermore, ZnS@GMs induce immunogenic cell death, which triggers dendritic cell maturation, cytotoxic T cell infiltration, and macrophage repolarization, thereby enhancing the efficacy of anti-PD-1 therapy. In a rabbit orthotopic liver tumor model, intra-arterial infusion of ZnS@GMs confirms potent antitumor effects and effective embolic performance. This work establishes ZnS@GMs as a multifunctional platform to overcome TAE resistance in HCC.