Xiaolin Huang

Natural enzymes achieve catalytic efficiency through the synergistic coupling of substrate activation and the efficient utilization of reactive intermediates. However, current nanozyme design paradigms focus predominantly on modulating substrate activation while overlooking the efficient utilization of highly reactive intermediates─a limitation that severely constrains substantial gains in catalytic activity. Inspired by the frustrated Lewis pair (FLP) composition of Fe2+ and tetrahydrobiopterin in tryptophan hydroxylase, we propose an FLP engineering approach to integrate 2,5-pyrazine-dicarboxylic acid (Pz) into the Materials of Institut Lavoisier-101 metal–organic framework (MIL-101(Fe)-H MOF) to construct MIL-101(Fe)-Pz MOF. This construct features pyrazine-nitrogen as a Lewis base and unsaturated Fe sites as Lewis acids. Compared with the Lewis acid-only MIL-101(Fe)-H MOF control, the as-fabricated FLP substantially accelerated the peroxidase-like activity of MIL-101(Fe)-Pz MOF, increasing the maximum reaction velocity by 4.83-fold when H2O2 was used as the substrate and by 17.88-fold when 3,3′,5,5′-tetramethylbenzidine (TMB) was used as the substrate. Combined experimental and theoretical analyses revealed that the distinct electronic interactions within FLP facilitate electron transfer, promote H2O2 activation, improve hydroxyl radical utilization, and lower the reaction energy barrier, thereby boosting the reaction kinetics. This work highlights the indispensable role of substrate activation and active intermediate utilization in enhancing nanozyme performance and also provides guidance for the design of next-generation bioinspired nanozymes.

Traumatic brain injury (TBI) requires a rapid and objective assessment; however, current diagnostic methodologies are constrained by subjectivity, reliance on imaging techniques, and insufficient sensitivity for the early detection of biomarkers. In this study, we present a click-chemistry-enhanced dynamic light scattering (DLS) immunoassay for the ultrasensitive detection of glial fibrillary acidic protein (GFAP), a clinically significant blood biomarker for brain injury. Unlike conventional DLS immunoassays, which rely on weak antigen–antibody interactions to drive DLS probe aggregation, the proposed approach transforms immunorecognition into a rapid covalent amplification process through click chemistry. A systematic comparison of three click-chemistry-driven aggregation reactions demonstrated that faster association kinetics led to more efficient probe aggregation and stronger signal amplification. On this basis, the optimized inverse electron-demand Diels–Alder reaction (IEDDA)-enhanced DLS immunoassay exhibits the highest sensitivity for GFAP detection, achieving a limit of detection of 210 fg mL–1, which is 109-fold and 348-fold lower than that of conventional DLS immunoassays and ELISA methods, respectively. The detection time of the proposed method was only 26 min. Additionally, the IEDDA-enhanced DLS immunoassay exhibits favorable performance in the analysis of clinical serum samples. In conclusion, this study introduces an effective signal amplification strategy utilizing click chemistry to enhance the sensitivity of DLS immunoassays, thereby providing a promising analytical platform for the rapid assessment of TBI.

Interleukin-2 (IL-2) immunotherapy offers considerable potential for metastatic cancers; however, its efficacy is limited by low response rates, dose-dependent toxicity, short half-life, poor tumor accumulation, and off-target immune activation. In this work, we present a biohybrid microrobot (IL-2@Z/C/A) engineered through biomimetic mineralization of IL-2 variant-secreting Escherichia coli Nissle 1917 (EcN) with a zeolitic imidazolate framework-8 (ZIF-8) shell coloaded with an aggregation-induced emission photosensitizer and catalase. The ZIF-8 coating preserves bacterial viability tumor-homing capability while preventing premature drug leakage and systemic exposure, thus minimizing off-target effects. Upon accumulation in the acidic tumor microenvironment (TME), the framework degrades to release engineered bacteria and therapeutic cargo. Locally delivered zinc ion release, light-triggered reactive oxygen species and EcN derived pathogen-associated molecular patterns act synergistically to induce Cle-caspase/GSDMD mediated pyroptosis, resulting in immunogenic cell death accompanied by damage-associated molecular pattern release and pro-inflammatory cytokine production. Simultaneously, catalase-driven oxygen generation alleviates hypoxia and suppresses HIF-1α-induced immunosuppression. In combination with PD-L1 blockade, IL-2@Z/C/A achieves near-complete tumor regression in a B16F10 melanoma model via a coordinated immune cascade: pyroptosis-mediated antigen exposure primes adaptive immunity, hypoxia reversal counteracts immunosuppression, and sustained local IL-2 release reverses T cell exhaustion, collectively reprogramming the immunosuppressive TME and eliciting strong antitumor immunity. This work establishes a distinct paradigm for spatially controlled immunotherapy and highlights the potential of this biohybrid microrobot in converting immunologically “cold” tumors into responsive niches.

The integration of accurate detection and immediate bactericidal in a single platform significantly enhances pathogen monitoring and control capabilities, but nanomaterial functional compatibility remains a major challenge. Here, we developed a multifunctional nanoplatform integrating multimode flexible detection and magnetic aggregation‐induced sterilization by utilizing the synergistic effect of quinone–phenol grafting nanozymes loaded with Pt single atoms (Pt SA@Q‐ACDs) and magnetic carbon dots (Fe ₃ O ₄ @DCDs). In Pt SA@Q‐ACDs, Pt SA increased the electron transfer from the quinone–phenol system, and the hydroxyl and pyridine state N defects sequentially synergized to form a double anchor site, the energy barrier for reducing H ₂ O ₂ was reduced, constituting a “1 + 1 > 2” bicatalytic system, which improved signal output and sterilization efficiency. Fe ₃ O ₄ @DCD enriches target bacteria through magnetic induction, dramatically reduces background interference, and increases the sterilization efficiency to 100% while realizing the detection of pathogenic bacteria at the single‐cell level. Complementing this, we designed an intelligent portable device capable of dynamically switching and interpreting multimodal signals, enabling adaptable field deployment. The multifunctional platform can realize early warning from food processing to the terminal, combined with high bactericidal efficiency, and can implement “closed‐loop monitoring” for pathogenic bacteria in an all‐round way, which has great potential.

Foodborne pathogens present significant public health risks, demanding sensitive on-site detection and effective antibacterial strategies. To address this, we synthesized magnetic-gold plasmonic blackbody (MNP@GPB) nanocomposites by coating a gold/polydopamine hybrid layer onto magnetic nanoparticles (MNPs) via in situ redox polymerization. The resulting MNP@GPBs exhibited excellent colloidal stability, broadband absorption, rapid magnetic responsiveness, and efficient photothermal conversion. Leveraging these properties, we engineered multifunctional probes for magnetic enrichment, colorimetric and photothermal signal generation, and antibacterial action in immunochromatographic assays (ICAs) for sensitive detection and simultaneous inactivation of Salmonella typhimurium. The limits of detection for MNP@GPB-ICA in the colorimetric and photothermal formats were 1.4 × 10³ and 3.4 × 10² CFU/mL, respectively, representing approximately 8-fold and 32-fold improvements in sensitivity over gold nanoparticle-based-ICA. Notably, near-complete inactivation of residual S. typhimurium on the test line was achieved after near-infrared irradiation, substantially reducing the risk of secondary contamination from discarded strips. MNP@GPBs thus represent a transformative platform unifying diagnostic signaling with antibacterial functionality for food safety monitoring.