Yanling Song

Controllable synthesis of two-dimensional (2D) platinum (Pt)-based nanomaterials with high photothermal conversion property for near-infrared (NIR) photothermal tumor therapy (PTT) is highly desired yet challenging. Herein, we report iodide (I–)-engineered Pt-antimony nanosheets (PtSbI NSs) with an ultrathin banana-slice-shaped profile for PTT. These PtSbI NSs exhibit dual phototherapeutic functions including outstanding photothermal conversion efficiency (49.6%) versus PtSbI nanoparticles (24.2%), PtSb NSs (29.0%), and commercial Au NSs (10.7%) as well as excellent photothermal stability. When functionalized with aptamers targeting the tumor biomarker EpCAM, they can serve as a tumor-targeted nanozyme. Through reactive oxygen species generation, they effectively mitigate tumor hypoxia, induce selective tumor cell apoptosis, and facilitate synergistic photothermal–catalytic therapy, leading to an 83.3% reduction in tumor weight and a significant extension of survival in 4T1 breast cancer-bearing mice. This work is of great significance for advancing the synthesis and functionalization of 2D Pt-based nanomaterials employed in the PTT field and beyond.

Glycosylated RNAs (glycoRNAs) reside on the cell surface with their functions largely unexplored. Here, we show that extracellular vesicles (EVs) carry glycoRNAs with distinct sequence diversity, vesicle type specificity and transfer dynamics. By metabolically tagging glycoRNAs with bioorthogonal handles, we selectively enrich and sequence EV-associated glycoRNAs, identifying specific glycoRNA species and expanding the EV glycoRNA landscape. We further develop a proximity-based imaging strategy to track glycoRNAs, revealing that glycoRNA repertoires in large EVs vary with cell type and passage, whereas small EVs display distinct profiles indicative of vesicle-specific sorting. Functionally, EVs deliver glycoRNAs into recipient cells and glycoRNAs are subsequently detected in recipient cell-derived EVs, reflecting contributions from newly synthesized glycoRNAs and others that may be associated with donor EVs. Notably, hybridization-based glycoRNA blockade can heavily reduce EV uptake, highlighting glycoRNAs as potentially actionable targets for modulating EV-cell communication. These findings expand the glycoRNA landscape and suggest EV glycoRNAs are biomarkers of cell state and regulators of vesicle tropism.

Extracellular vesicles (EVs) are cell-derived nanoparticles that mediate intercellular communication, whereas circulating tumour-derived EVs (ctEVs) promote tumour progression. However, their circadian dynamics remain poorly understood owing to the lack of tools capable of resolving vesicle biogenesis dynamics. Here we introduce ctEV-CLOCK, a strategy enabling 12-h resolution isolation of nascent ctEVs. The method integrates metabolic glycoengineering-based timestamping with tumour-marker-guided selective click tagging, achieving enrichment of ctEV populations within defined time windows. Using this approach, we uncover circadian oscillations in ctEV abundance and functional properties across multiple mouse tumour models. These oscillations are accompanied by time-of-day-dependent alterations in vesicle protein profiles. Importantly, synchronizing targeted therapy with peak ctEV protein abundance markedly enhances therapeutic efficacy. Together, these findings position ctEV circadian dynamics as a regulatory layer in tumour biology and provide a framework for circadian-aligned cancer chronotherapy beyond immune-focused strategies.

Extracellular vesicles (EVs) have emerged as a prominent and rapidly evolving class of biomarkers, garnering an increasing amount of attention in recent years. The analysis of diverse EV-derived biomolecules, including proteins, mRNA, and miRNA, has driven the development of numerous innovative analytical technologies for EV detection. Nevertheless, despite significant advancements, most current EV analysis methods still require substantial improvements to address critical limitations, such as operational complexity, insufficient sensitivity, and the persistent issue of false-positive signals. In this study, we present a targeted fusion and nonenzymatic amplification strategy for ultrasensitive detection of tumor-derived EV miRNAs. The proposed approach integrates an aptamer-anchored liposome system that facilitates specific recognition and fusion with tumor EVs, coupled with a spatial confinement nonenzymatic signal amplification system to significantly enhance detection sensitivity. In conjunction with flow cytometry, the platform demonstrates a detection limit of 4 ng/mL for EV- associated proteins (0.2 fM for EV miR-21) and effectively discriminates cancer patients from healthy controls. This innovative strategy shows substantial promise for diverse biomedical applications, potentially revolutionizing early cancer diagnosis, metastasis monitoring, and prognostic evaluation while also offering opportunities for the detection and management of various other diseases.

Extracellular vesicles (EVs) have emerged as promising biomarkers for monitoring physiological homeostasis and pathological progression. However, current analytic methods face limitations in preserving spatial information about EVs and their intricate connections to parental and recipient cells. Here, we present Spatial-EV-seq, a method for in situ spatial profiling of EVs within their native microenvironmental context. Spatial-EV-seq uses an antibody-engineered capture interface to preserve EVs' spatial distribution, followed by rolling circle amplification with EV surface-binding aptamers, enabling fluorescence imaging and molecular profiling of individual EVs. The method integrates ultrasensitive EV profiling, molecular subtyping and high-resolution spatial mapping with transcriptomics to resolve location-specific EV-cell communication networks. In an anti-PD1-treated breast cancer mouse model, we uncover a spatially orchestrated immunosuppressive axis: PDL1⁺ EV-enriched zones drive CD8⁺ T cell dysfunction, establishing immune-privileged niches, whereas PDL1⁺ EV-depleted regions preserve immunocompetence and therapeutic sensitivity. Spatial-EV-seq offers insights into EV-mediated mechanisms and unlocks avenues for precision diagnostics and therapeutics.

Functional DNA nanoassemblies (fDns) hold promise for biomedical and translational applications, but broader deployment is limited by manufacturing barriers that constrain scalability, reproducibility, and stability. Current biosynthetic approaches rely heavily on downstream enzymatic processing and purification, which dominate economic, operational, and environmental costs at scale. Here we report an integrated manufacturing strategy that combines programmed circular single-stranded DNA with bacteriophage-driven biosynthesis to enable direct production of high-quality fDns with minimal post-assembly purification. By reducing reliance on purification as a major bottleneck, this approach delivers topology-enhanced stability, high assembly efficiency, and batch reproducibility, achieving sub-gram laboratory production at ~$6 per milligram while suggesting a pathway toward scalable manufacturing. We demonstrate versatility through 11 distinct fDns, including an aptamer-functionalized construct that neutralizes SARS-CoV-2 pseudovirus and authentic Omicron variants in cellular and animal models. This work provides a cost-effective, scalable manufacturing framework for fDns, advancing their sustainable and reproducible deployment across life-science applications.

Immune cell therapy has emerged as a highly promising modality in cancer immunotherapy. Effective in vivo cell tracking is essential for the real-time assessment of cell distribution, viability, and proliferation, providing critical insights into both fundamental research and clinical translation. However, conventional fluorescence imaging often suffers from limited sensitivity due to high background signals and poor tissue penetration. Consequently, activatable near-infrared (NIR) fluorescence imaging has garnered significant attention. By leveraging the NIR window to minimize tissue attenuation and autofluorescence, these probes offer superior depth penetration. Unlike “always-on” probes that generate nonspecific background noise, activatable probes remain quenched until triggered by specific biomarkers, thereby substantially improving the signal-to-noise ratio. This review summarizes key activation mechanisms and synthetic strategies for these probes, highlighting their application in immune cell monitoring. We also discuss current challenges, such as identifying molecular targets, and envision that advancing activatable NIR probes will play a pivotal role in optimizing clinical immunotherapy.

Among others, polysaccharide-functionalized macroporous silica microspheres are predominantly employed as chiral stationary phases (CSPs) in HPLC. Conventionally, such macroporous phases are prepared through pore-widening post-treatments of polydispersed mesoporous silica microspheres and typically exhibit a broad distribution of pore size and multimodal pore structures. This post-treatment manufacturing strategy and the resultant enlarged pores have limited the chiral separation performance of current CSPs. Herein, a droplet microfluidic synthesis platform was utilized to integrate sol-gel chemistry with a phase-separation process, in order to realize precision manufacture of monodisperse macroporous silica with monomodal pore structure and narrow pore size distribution, in a single shot. Following microfluidic synthesis, a monodisperse chiral stationary phase (Mono-CSP) functionalized with cellulose tris(3,5-dimethylphenylcarbamate) was prepared and compared with the classical Chiralcel OD-H column with the same polysaccharide functional group but based on conventional macroporous silica. Van Deemter curves demonstrated pronouncedly improved peak efficiencies, as a result of the reduced eddy diffusion on Mono-CSP. Systematic comparison with the Chiralcel OD-H phase indicates that such monodispersed CSP realized significantly improved resolution in enantioseparation. In particular, the Mono-CSP presented universally enhanced retention toward racemates of diverse properties, including acidic, neutral, and basic compounds. Of all the 42 enantiomers investigated, spanning alcohols, ketones, aldehydes, amines, esters, ethers, and organic acids, 90.5% showed higher retention factors (k₁), and 93% realized enhanced resolution on the Mono-CSP than on the polydispersed Chiralcel with the same chiral stationary phase chemistry. The current microfluidic precision manufacturing methodology holds promise for extension to the preparation of multiple types of high-performance chiral chromatographic stationary phases.

Accurate identification of urinary pathogens is essential for the timely diagnosis and effective management of urinary tract infections (UTIs). Bacterial extracellular vesicles (bEVs), which carry pathogen-specific surface antigens, represent an attractive diagnostic target. However, their clinical translation is impeded by the time-consuming and labor-intensive isolation process (typically requiring up to 72 h) from complex biological samples such as urine. To overcome this limitation, we report an intelligent colorimetric sensor array capable of decoding pathogen-specific biochemical signatures for the direct, accurate and rapid identification of bEVs in UTIs. It is realized by inventing a three-dimensional biomimetic nanozyme comprising TiO₂ nanoparticles-bridged Hemin molecules anchored on graphdiyne with a sandwich configuration, thus enabling both selective capture of bEVs and enhanced peroxidase (POD)-like catalytic activity. The specificity arises from the atomic Fe centers in Hemin molecules, which establish stable coordination interactions with the O-antigens of lipopolysaccharides on the bEV surface. Upon bEV recognition, the biomimetic nanozyme exhibits pH-dependent suppression of POD-like activity, generating distinctive colorimetric fingerprints. Coupled with machine learning, the platform accurately classifies bEV subtypes. Clinical validations demonstrate a diagnostic accuracy of 100.0% within 30 min, underscoring the promising point-of-care UTI management.