Ming Ma

As tumor-associated biomarkers, proteins on small extracellular vesicles (sEVs) play a critical role in revealing tumor subtypes and disease progression. Nevertheless, the rapid isolation of sEVs and the quantitative detection of their surface proteins remain challenging. In this study, we developed a nanozyme (PB-MIP-PEG) array sensing platform based on molecular imprinting technology (MIT), which can efficiently enrich sEVs and simultaneously detect three proteins: CD20, CD19, and PD-L1. Fe₃O₄@TiO₂ magnetic beads interact with phosphate groups in the sEVs phospholipid bilayer and, under an external magnetic field, achieve effective separation from complex samples. Prussian blue (PB) nanozymes with peroxidase (POD)-like activity, coated with a silicon dioxide (SiO₂) imprinting layer, showed enhanced enrichment toward 3,3',5,5'-tetramethylbenzidine (TMB), which contributed to improved catalytic activity and detection sensitivity. Furthermore, density functional theory (DFT) and molecular dynamics (MD) simulations further revealed that hydrogen bonding and π-π stacking are the dominant interactions during the imprinting process. By integration of colorimetric imaging with a position-encoding system and employing a convolutional neural network-long short-term memory (CNN-LSTM) model for automated feature extraction, the concentrations of CD20, CD19, and PD-L1 were rapidly distinguished. This array sensing platform, which integrates molecularly imprinted nanozymes with neural network models, provides a new approach for the intelligent analysis of sEVs surface proteins and demonstrates a potential application value in lymphoma-related monitoring.

Extracellular vesicle (EV) microRNAs (miRNAs) are promising liquid biopsy biomarkers for non‐invasive diagnosis, monitoring, and therapeutic evaluation of cancer. However, sensitive EV miRNA detection is hindered by complex pre‐analytical processing. Here, the authors present an anionic liposome (AL) assisted membrane fusion strategy enabling one‐step multiplexed quantification of EV miRNAs directly from plasma without EV isolation or RNA extraction, termed EValarm (Anionic Liposome Assisted miRNAs Monitoring for Extracellular Vesicles). Liposomes encapsulating probes are prepared using a microfluidic chip, achieving catalytic signal amplification after target recognition of miRNA. Systematic lipid screening identified ALs as optimal carriers, exhibiting minimal background and superior sensitivity compared to cationic and neutral liposomes. The AL‐based assay delivered accuracy comparable to quantitative PCR with a streamlined workflow. Applied to 106 clinical samples from lymphoma patients and healthy controls, integration with artificial intelligence achieved high accuracy (AUC > 0.99). In summary, this study demonstrates a platform enabling direct and sensitive plasma EV miRNA detection, offering strong potential for clinical translation in cancer liquid biopsy.

Lymph nodes (LNs), as critical components of the lymphatic system, serve as the primary site for adaptive immune responses and represent important therapeutic targets for various diseases. Studies demonstrate that LN metastasis of malignant tumors constitutes a major cause of mortality in cancer patients, highlighting the crucial importance of achieving precise drug accumulation in LNs for enhanced therapeutic efficacy. While significant progress has been made in optimizing lymph‐targeting capabilities through rational design of nanoparticle‐based drug delivery systems, the immunological mechanisms and regulatory pathways involved remain to be fully elucidated. This review focuses on elucidating the interaction mechanisms between nanoparticles and immune cells within LNs through investigating the distribution, retention, and immunomodulatory effects of nanodrugs. By integrating tumor microenvironment characteristics, we aim to precisely regulate the targeted delivery behavior of nanoparticles, thereby advancing the development of enhanced cancer immunotherapy.

Ischemia–reperfusion is a rapidly evolving cascade that involves a variety of metabolic shifts whose precise timing and sequential order are still poorly understood. Clarifying these dynamics is critical for understanding the core injury trajectory of stroke and for refining time-delimited therapeutic interventions. More broadly, continuous in situ monitoring of the middle-cerebral-artery occlusion process at the system level has not yet been achieved. Here, we report the first single-subject high-resolution spatiotemporal resolution metabolic maps of the ultra-early phase of ischemic stroke in a rodent model. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging mapped a metabolic abnormality area in the ischemic hemisphere that propagates from the striatum to the cortex. Microdialysis probes were then stereotaxically implanted within this metabolic abnormality area, capturing 10,429 metabolites that resolved into 16 temporally distinct trajectories aligned with probe insertion, ischemic injury, and reperfusion injury. Analysis of specific metabolic pathways mainly revealed that the delayed clearance of metabolic waste (urea and tryptamine) during early reperfusion, the transient attenuation of the citrate-to-oxaloacetate buffering gradient within the TCA cycle, and the accumulation of extracellular branched-chain amino acids all play crucial roles in shaping the injury trajectory. Simultaneously, the depletion of cellular repair mechanisms (pyrimidine synthesis) in the early phase of reperfusion also warrants our attention. These findings provide novel insights into the molecular basis and mechanisms of ischemia–reperfusion and offer a comprehensive resource for further investigation.

Prussian blue nanoparticles (PBNPs) have emerged as versatile nanozymes with reactive oxygen species (ROS)-scavenging capabilities, predominantly applied in antioxidant therapies. In this work, we present a combined theoretical and experimental study demonstrating that modulating Fe coordination environments can fundamentally reconfigure PBNPs’ catalytic properties, enabling ROS generation and pro-oxidative functionality. Ab initio molecular dynamics revealed different H₂O₂ lysis mechanisms at Fe sites with varying coordination numbers: Low-coordinated center (FeN₄) induced hydrogen atom transfer to form Fe=O species, while high-coordinated FeN₅ generated ·OH radicals via H⁺-assisted homolysis under acidic conditions. Guided by calculations, Cs-doped PBNPs (Cs-PBs) with elevated coordination numbers were synthesized via alkali cation stoichiometric control, leveraging high distribution coefficient and low hydration energy of Cs⁺. Experimental results confirmed radical generation in Cs-PBs aligned with theoretical predictions. The size-optimized Cs-PBs demonstrated ultrahigh peroxidase-like activity (1182.26 U·mg^-1) and outperformed ROS generating properties in both pollutant degradation and chemodynamic therapy. This work redefines PBNPs’ catalytic potential beyond conventional antioxidant roles, and lays the foundation for innovative environmental and therapeutic solutions.

To address the complexity of structural design and synergistic optimization of biological effects of nanozymes in the field of oncology therapy, this study constructed a nanozymes platform (Pt@E5) with a facile and highly efficient preparation process for precision targeting of lymphoma. Pt@E5 nanozymes assemblies were directly prepared by a one-step reduction method, and the modification of E5 peptide ensured the dimensional homogeneity and stability of the platinum nanoparticles. This nano enzymatic platform combines dual enzyme activity with chemokine receptor 4 (CXCR4) targeting. It can inhibit tumor metastasis by targeting CXCR4 and thus specifically blocking the CXCR4/CXCL12 (stromal cell derived factor 1α) signaling pathway. In addition, it induces mitochondria mediated apoptosis and immunogenic cell death (ICD) in tumor cells by catalyzing the production of reactive oxygen species (ROS) using dual enzyme activity. In a mouse lymphoma model, the therapeutic results showed that Pt@E5 treatment effectively remodeled the tumor immunosuppressive microenvironment by promoting cytotoxic T cell infiltration (CTLs) and reducing regulatory T cell (Treg) levels. It also eliminated A20 cells from the bone marrow and peripheral blood, leading to significant tumor regression compared to the control group. In conclusion, this study offers a promising translational strategy for the multifaceted collaborative treatment of diffuse large B-cell lymphoma (DLBCL) based on a simple nanozyme-peptide assembly.