Self-assembled metallacages with stimuli-responsive structural transformation and optical tunability present great potential in sensing and detection applications. Herein, the design and synthesis of a multi-stimuli-responsive Pd₂L₄-type metallacage (MC) are reported, which is constructed through the coordination-driven self-assembly of triphenylamine-based dipyridyl ligand and Pd(II) ions. MC undergoes reversible disassembly upon interaction with specific basic organic ligands and reassembles in the presence of acidic reagents. MC demonstrates an apparent fluorescence resonance energy transfer (FRET) emission enhancement in the presence of naphthalene disulfonate (NDS) isomers and highly selective binding towards four NDS isomers, where, only upon binding with 2,6-NDS, a solution-to-gel transition is observed, due to the specific electrostatic and π–π interactions between MC and 2,6-NDS. Significantly, MC enables highly selective and rapid detection of thiol-containing amino acids with a detection limit of 1.22 × 10⁻⁶ M via a self-destructive fluorescence detection mechanism. A facile test strip based on this cage has also been developed to detect cysteine visually. This work widens the application scopes of self-assembled metallacages and opens new perspectives for building stimuli-responsive supramolecular coordination complexes.

The near-infrared-IIx (NIR-IIx, 1400–1500 nm) sub-window theoretically surpasses the conventional near-infrared-II (NIR-II) region in optical imaging fidelity but requires luminophores with high brightness and stability. Herein, we present a germanium-engineered xanthene fluorophore (EGe5) featuring extended π-conjugation and a planarized core, as unequivocally resolved by single-crystal X-ray analysis. The vertically aligned methyl groups sterically hinder molecular vibration, while germanium's heavy-atom effect enhances radiative decay, collectively resulting in a 3.3% quantum yield in the NIR-II window and high NIR-IIx brightness. In addition, EGe5 retains nearly unchanged fluorescence intensity for over 12 h under harsh oxidative and reductive conditions. In vivo studies confirm its prolonged circulation time (>60 min) is enough for persistent NIR-IIx fluorescent angiography, which helps to identify the intestinal obstruction by tracing the diseased intestinal wall blood vessels. Furthermore, EGe5-PEG₄₅ achieves rapid renal clearance and enables high-contrast excretory urography, dynamically tracking hydronephrosis progression in ureteral obstruction models. This work provides a molecular design paradigm for NIR-IIx probes and a versatile tool for minimally invasive diagnosis of gastrointestinal/urological diseases.

Non-neoplastic diseases, such as cardiovascular, neurodegenerative, metabolic, and inflammatory disorders, are major global health challenges with complex pathophysiologies that demand precise and innovative therapeutic strategies. Nanozymes, artificial nanomaterials with enzyme-like catalytic functions, have recently emerged as promising candidates for such interventions. Distinguished by their programmable structures, tunable activities, and excellent biocompatibility, nanozymes can mimic multiple natural enzymes (e.g., superoxide dismutase, catalase, and peroxidase) to modulate oxidative stress and inflammation. Beyond catalytic activity, their functional integration enables immune regulation and metabolic reprogramming, facilitating multilevel (molecular to tissue) microenvironmental remodeling. This review highlights recent progress in nanozyme development for non-neoplastic disease therapy, emphasizing structure–function relationships, activity regulation in pathological conditions, and mechanistic roles in disrupting the oxidative stress–inflammation–immune dysregulation loop. We further summarize representative applications across cardiovascular diseases, neurodegenerative conditions, metabolic disorders, and inflammatory pathologies, focusing on advances in targeted delivery, responsive release, and multimodal theranostics. These insights collectively underline the transformative potential of nanozymes in next-generation precision medicine.

Traditional fluorescent materials for information encryption have drawbacks such as low resolution and cumbersome process of information loading. We have developed an α-amylase-stimulated responsive fluorescent hydrogel system, which was used to store information with arbitrary architectures through combining 3D printing technology. By controlling the concentration of α-amylase to tune the fluorescence of the hydrogel, various types of information on the hydrogel at specific times can be obtained. Multiple dynamic encryptions of information can be easily performed, during which false information may be generated as a means to further improve the security of information storage. Moreover, displaying information from a two-dimensional to a three-dimensional plane of this responsive fluorescent hydrogel broadens the method of information storage and encryption. The introduction of a multicolor system and 3D printing of bacteria that secrete α-amylase in situ will provide a new design strategy for information encryption design.

Treponema pallidum (T. pallidum) causes syphilis, a sexually transmitted disease that leads to multi-organ complications and even death. The lack of technology for tracing live T. pallidum greatly impedes understanding of the pathogenesis of T. pallidum. Herein, we firstly designed and developed an in situ high-resolution imaging strategy to trace live T. pallidum using catalyst-free bioorthogonal labeling with aggregation-induced emission luminogens (AIEgens). An activated alkyne-containing AIEgen, 5-(4-(diphenylamino) phenylthiophene-2-ynylidene) ketone (named TPA-TA), was directly reacted with the proteins of T. pallidum through metal-free click chemistry, without affecting T. pallidum’s activity. Specially, TPA-TA enables high-resolution imaging of live T. pallidum with low background. Both whole phcagocytosis of T. pallidum by THP-1 cells and dissemination in lesions could be monitored in real time, which helped clarify the interaction between the immune clearance and escape of T. pallidum. In conclusion, this catalyst-free bioorthogonal labeling strategy enriches the toolkit for exploring and understanding syphilis-related pathologies.

The structural precision of living supramolecular polymerization processes is dictated by nucleation control, conventionally achieved through kinetic trapping of monomers in metastable aggregates or inactive molecular states. However, current strategies for living supramolecular polymerization, relying on bulk-phase kinetic trapping of monomers, homogenize assembly pathways and hinder hierarchical control. By leveraging the interfacial adsorption of amphiphilic molecules at the liquid–liquid interface, we engineered a self-limiting single-molecule film from PDIOH 1 that elevates the nucleation energy barrier, suppressing premature polymerization while enabling pathway-specific control over hierarchical self-assembly. The dynamic monolayer drives surface-catalyzed secondary nucleation at the liquid–liquid interface, programmably yielding epitaxially aligned 2D hierarchical architectures. Introducing interfacial seeds directs epitaxial growth of 2D hierarchical architectures with uniform shapes during living supramolecular polymerization. Remarkably, the excitation fluence–dependent transient absorption studies demonstrate that 2D hierarchical architectures exhibit a much larger exciton diffusion coefficient than that of disorganized fibers formed in the bulk solution. This work provides an interfacial strategy, enabling controllable assembly of 2D hierarchical materials via living supramolecular polymerization.

Aggregation-induced emission (AIE) has emerged as a powerful tool for the design of next-generation intelligent theranostic systems. AIE luminogens (AIEgens) exhibit exceptional sensitivity and signal fidelity in complex biological environments through the restriction of intramolecular motion (RIM), which suppresses nonradiative decay and facilitates highly efficient fluorescence emission in the aggregated state. This review critically evaluates the recent integration of AIE materials into multifunctional theranostic systems, including near-infrared II (NIR-II) emissive nanoprobes for deep-tissue imaging, AIE-powered ELISA assays with femtomolar sensitivity, CRISPR-compatible detection platforms for real-time visualization of gene editing, and the emerging application of artificial intelligence (AI) for improved diagnostic accuracy and material design. Despite these breakthroughs, translational barriers—such as limited structural diversity, batch-to-batch variability, and the absence of comprehensive regulatory frameworks—still hinder clinical adoption. Addressing these obstacles through AI-driven molecular engineering, scalable synthetic methodologies, and standardized evaluation protocols will be pivotal for advancing AIE materials toward clinical implementation. This review not only consolidates recent progress but also provides a forward-looking perspective on the strategic directions and interdisciplinary collaborations necessary to translate AIE innovations from bench to bedside.

Stretchable organic solar cells (SOSCs) show remarkable promise to provide energy to wearable electronic devices. Despite the rigid organic solar cells (OSCs) have made power conversion efficiencies (PCEs) of over 20%, tensile properties of these high-performance active layers are often compromised and thus do not make them suitable for stretchable wearable electronic devices. In this regard, we designed a novel donor polymer, PBDTT-Fully-asy, with the fully asymmetric structure of the backbone and side chains, and incorporated it in PM6:Y6 blend to construct a stretchable light-harvesting active layer. Compared with a symmetric structure, the center of the fully asymmetric fused-ring is shifted, which can weaken self-aggregation. In addition, strong twisting and disruption of the aggregation can occur due to the side chain of the rigid benzene ring. Furthermore, the improved backbone coplanarity and increased π-conjugation are advantageous for improving the charge transfer ability and photovoltaic performance. Our obtained results suggest that incorporation of PBDTT-Fully-asy (10 wt%) can efficiently improve the stretchability and photovoltaic performance. Our proposed molecular design approach will contribute to the acceleration of high-performance stretchable.

The self-coiling behaviors of organic molecules in fluorinated solvents haven't been explored previously. As one particular type of fluorous solvent, polar fluorinated arenes are widely used in both academia and industry. In this report, several modern techniques, including visual observation, concentration-dependent UV-visible spectroscopy, concentration-dependent fluorescence spectroscopy and kinetics measurements, dynamic light scattering (DLS) tests, and theoretical calculations, are employed to examine the self-coiling and aggregation behaviors of two types of organic fluorescent probes with saturated aliphatic chains in three polar fluorinated arenes. In contrast to in aqueous solutions, their behaviors differ significantly: the single-headed probes in polar fluorinated arenes maintain a stretched hatpin conformation, form aggregates at low concentrations, and form excimers at higher concentrations; most double-headed probes tend to self-coil in these solvents, but the optimal conformation depends on the chain length and can form excimers at very low concentrations, while their CAgCs are comparable to those of single-headed probes. As an exciting discovery, the macrolactonization reaction of 8-hydroxyoctanoic acid in trifluorotoluene has been obviously improved by molecular self-coiling. Therefore, our discoveries may provide guidance for the regulation of the synthesis of macrocycles in such solvents in the future.

A multifunctional nanoplatform (USiCeCurAu) has been developed that integrates upconversion nanoparticles (UCNPs), gold nanoparticles (AuNPs), cerium oxide (CeO₂), and a thioketal-curcumin-triphenylphosphonium conjugate (TK-CUR-TPP) to enable synergistic tumor therapy via photodynamic (PDT), chemodynamic (CDT), and mild photothermal therapy (mPTT). In this strategy, AuNPs attached to the surface serve as a “pore locker”, cloaking CeO₂ and CUR before entering tumor cells. UCNPs convert near-infrared (NIR) light into UV and visible light emission, simultaneously initiating AuNP aggregation via photoclick chemistry, CeO₂-mediated reactive oxygen species (ROS) generation, and TPP-CUR-driven PDT. The CeO₂ amplifies oxidative stress by depleting glutathione (GSH) and catalyzing ROS production (O₂·⁻ and ·OH), while releasing oxygen to relieve tumor hypoxia. The release of TPP-CUR not merely resumes the negativity of the surface, but also disrupts mitochondrial function and downregulates heat shock proteins (HSPs), further sensitizing tumor cells to mPTT (∼45°C) performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion. Importantly, ROS-scavenging ability post-PTT of CeO₂ has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation. This fully integrated, light- and ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice, reducing tumor volume from 185 to 27 mm³ following a single tail-vein injection.

While traditional bulk hydrogels have been widely used in 3D bioprinting for tissue engineering, engineered cell-loaded scaffolds still fall short of expectations because their nanoscale molecular networks impede cell function. Microgels, as micron-sized hydrogel materials, offer significant advantages in enhancing mass transport and tissue permeability, while concurrently promoting cellular proliferation, migration, and differentiation. Incorporating microgels as bioinks into 3D bioprinting enables customization of shape, mechanical properties, and functionality, significantly expanding the applications of hydrogel materials and addressing diverse bioprinting needs. Hierarchically porous scaffolds formed by microgel assembly leverage dual-scale porosity: nanoporosity inherent in the material and microporosity originating from the assembly. This unique structure promotes tissue regeneration and facilitates microtissue assembly. This review provides an overview of microgel fabrication techniques, describing their role as carriers for cells and biomolecules, as well as their applications in 3D biofabrication. Notably, we throughout present the application of microgels in 3D biofabrication. Finally, we provide an outlook on the potential applications of microgels in biomedical engineering and their integration with emerging printing technologies.

Organic electronic devices offer unique advantages in flexible, solution-processable, and cost-effective applications, where molecular stacking directly determines the optoelectronic properties of materials and devices. Heterojunction microstructures, which serve as the fundamental building blocks for controlling photoexciton dynamics and charge transport processes, have emerged as a critical feature to govern the coordination of exciton dynamics, charge transport, and multifunctional coupling in organic semiconductors. In this review, we provide a comprehensive overview of recent advances in heterojunction microstructures for modulating optoelectronic properties, offering valuable insights for high-performance and multifunctional organic electronics applications. We begin by introducing the fundamentals of heterojunction aggregation and its role in modulating physical processes through electronic structure and carrier transport engineering. Subsequently, we review recent progress in heterojunction aggregation within organic electronics, encompassing performance optimization and multifunctional extensions. In addition, we summarize four key strategies for constructing heterojunction microstructures in organic electronic devices. Finally, we outline future perspectives, emphasizing the critical need for deeper understanding of aggregation dynamics and the development of scalable fabrication approaches for heterojunction-structured films in next-generation intelligent devices.

Halide perovskites are promising candidates for optoelectronic devices, but their solution-processed films frequently suffer from solute aggregation, crystalline disorder, and random orientation, that is, defects that significantly compromise device performance. These issues arise from complex multiscale interactions during film formation, where macroscopic mechanical forces could hypothetically influence atomic-scale assembly. This review elucidates the critical role of multiscale mechanical coupling (linking surface/interface mechanics, fluid dynamics, and crystallization kinetics) in governing perovskite film quality, which ultimately enhanced the uniformity of film thickness, photoelectric performance, and long-term stability. We first analyze how solvent evaporation, interfacial energy, and flow-induced shear shape the spatiotemporal evolution of solute distribution and crystal growth. Building on this understanding, we present mechanical regulation strategies aimed at directing film formation: modifying wettability through surfactants and surface energy modulators; manipulating flow behavior via Marangoni convection and shear stress; and mitigating interfacial stress through lattice and thermal expansion matching. To further enhance structural control, we highlight fabrication techniques that couple multiple external fields (e.g., thermal, electrical, mechanical, and chemical fields) and leverage in situ characterization for real-time feedback. Finally, we explore machine learning-assisted multiscale modeling as a powerful tool to connect atomic interactions with macroscopic processing variables, enabling predictive optimization. By integrating these insights, this review establishes a unified framework for guiding high-quality, scalable perovskite film fabrication toward industrial deployment.

Merging tetraphenylethylene (TPE) into cyclic skeletons endows fluorescent sensing capabilities for pillar[6]arenes aggregates, but results in losing their host–guest recognition function in dilute solutions. Inspired by natural enzymes, here we describe a series of TPE-based cyclo[6]arenes (termed TPz, TDz, and TTz) with endo-functionalized cavities containing inward-directed diazine motifs (pyrazine, pyridazine, and phthalazine) that act as hydrogen-bond acceptor sites. Combining electrostatic potential analysis and host–guest binding studies reveals that subtle variations in these diazine motifs substantially affect charge distribution and hydrogen-bond interactions within the internal microenvironment. These differences translate into disparate host–guest affinities, with TTz exhibiting the optimal performance. Unlike TPz, which recognizes guests only in aggregate states, 1,2-diazine-modified TDz and TTz possess dual-state recognition functionality. They enable size-selective binding for cationic guests in dilute solutions and sensitive fluorescence detection of nitrophenol pollutants in aggregate states through a photoinduced electron transfer-driven static quenching mechanism. This study underscores the potential of 1,2-diazine motifs as transformative hydrogen-bond acceptors for biomimetic host models with emergent properties.

Precise enantiomer discrimination is crucial across diverse fields; however, developing a rapid and solvent-free strategy for chiral discrimination is still difficult to achieve. Here, we present a chirality-dependent Förster resonance energy transfer (FRET) system for enantiomer discrimination in the solid state. Perylene diimide (PDI) enantiomers serve as fluorescent selectands (guests), while chiral naphthalimide (NMI) or naphthalene diimide (NDI) act as chiral selectors (hosts). Photophysical studies reveal that host and guest with homochirality exhibit markedly enhanced fluorescence compared to heterochiral counterparts, attributed to more efficient FRET. In contrast, control experiments under FRET-suppressed conditions fail to effectively discern molecular chirality. Molecular dynamics simulations reveal that homochiral host and guest tend to adopt more compact molecular packing, thereby promoting FRET. This work provides a noncovalent fluorescence-based platform for real-time enantioselective recognition in the solid state.

In this work, a diphosphine chelator, 2-Ph₂PC₆H₄PH₂, containing both primary and tertiary phosphine donors, was used to create highly stable silver(I) nanoclusters through a dynamic ligand metathesis reaction. Taking advantage of thiolate-silver coordination polymers as synthetic precursors, we developed a viable synthetic approach to access Ag34 nanoclusters through dual proton and ligand exchange successfully. Owing to the stronger coordination ability of the bifunctional 2-Ph₂PC₆H₄PH₂ ligand, substitution results in the formation of thermodynamically stable Ag34 nanoclusters linked by fifteen 2-Ph₂PC₆H₄P²⁻ chelators. Notably, thiolates as structural templates rather than protective ligands play a crucial role in directing nanocluster construction. The Ag34 nanoclusters manifest highly efficient near-infrared photoluminescence peaked at ca. 800 nm with over 24% of quantum yield in fluid CH₂Cl₂ solution, arising mostly from ligand-to-metal charge transfer (³LMCT) and cluster-centered (³CC) triplet states. Solution-processable near-infrared organic light-emitting diodes (NIR-OLEDs) achieved high-efficiency near-infrared electroluminescence with an external quantum efficiency (EQE) of 10.2%. The unique synthetic approach can be extended to other metal systems, thereby expanding both the structural diversity and application potential of metal nanoclusters.

Retinal neovascularization (RNV) drives dual pathological cascades: structural destruction characterized by intraretinal/vitreous hemorrhages and tractional retinal detachment, alongside functional decline marked by progressive neurodegeneration and irreversible vision loss. Current clinical interventions for RNV face critical limitations in targeting specificity and therapeutic durability. To address this, we engineer magnesium acetyl taurate/thalidomide co-assembled nanoparticles (MT NPs) via Super-stable Pure Nanomedicine Formulation Technology (SPFT), constructing solvent-free, coordination-driven nanostructures with dual-drug loading. The MT NPs are further coated with transferrin-modified cell membrane vesicles (Tfm) to form targeted nanocomposites (Tfm@MT NPs). In oxygen-induced retinopathy (OIR) mouse models, Tfm@MT NPs demonstrated: (1) specific targeting to pathological vascular endothelia and retinal ganglion cells (RGCs) via transferrin receptor-mediated uptake, (2) sustained drug release exceeding 10 days, and (3) potent therapeutic effects in restoring visual functions. This study establishes a safe and effective targeted nanotherapeutic strategy for RNV, with significant translational potential for retinopathy treatment.

Reversing the tumor microenvironment (TME) from “cold” to “hot” tumor represents a pivotal strategy to overcome the clinical bottleneck of poor response rates to immunotherapy in solid tumors. Herein, we innovatively employed a macrophage bioreactor to induce M0 macrophage polarization and the secretion of functional extracellular vesicles (M1-EVs) through co-incubation with hollow mesoporous silica nanoparticles loaded with the aggregation-induced emission photothermal agent AXCB6 and the IDO1 inhibitor NLG919. Notably, this in-situ bioengineering approach preserves the inherent biological properties and activity stability of functional agents’ components. Upon near-infrared irradiation, AXCB6 induces direct tumor cell death via photothermal therapy (PTT) and elicits immunogenic cell death, which subsequently triggers both in-situ vaccine responses and systemic immunity. Concomitantly, NLG919 inhibits the activity of PTT-driven IDO1 overexpression, reversing tryptophan metabolism-mediated immune suppression. Additionally, bioengineered M1-EVs with inherent repolarization capacity further reshape the inflammatory microenvironment and synergize with IDO1 blockade to potentiate immune activation. Through this cascaded amplification, the triple combination therapy exhibits superior therapeutic efficacy and favorable safety profiles compared to monotherapy and dual-drug combinations in both in vitro and in vivo. These findings indicate that the EV-integrated multi-dimensional system offers a promising strategy for converting “cold” tumors to “hot” tumors via Poseidon's “trident” mechanism: PTT-mediated physical ablation—repolarization-driven TME remodeling—immune checkpoint intervention.

Multi-resonant (MR) emitters exhibit intrinsic narrowband emission, yet they often suffer severe spectral broadening at high doping concentrations in films, which hinders their commercial application in high-color-purity organic light-emitting diodes (OLEDs). Such spectral broadening is generally caused by shoulder peak enhancement, a puzzling phenomenon in aggregation state. Two typical MR backbones, carbonyl/nitrogen-based DNK and organoboron/nitrogen-based DBN, which exhibit different spectral behaviors in films, were thus investigated and compared as an example. The experimental results indicate that DNKs exhibit noticeable shoulder peak enhancement at high concentrations in films, while DBNs maintain consistent spectra under the same conditions. The results of our molecular dynamics (MD) simulations reveal that in the aggregation state, DNK π–π stacking forms, thus introducing a new fluorescent component. The emission of DNK dimers is estimated to be located around the intrinsic MR shoulder peak, leading to a concentration-dependent shoulder peak enhancement in OLEDs. Conversely, no dimer-like aggregation states are observed for DBN in films due to the presence of bulky side groups, leading to its concentration-independent fluorescence spectra. This work combines MD simulation with high-level quantum chemistry (QC) calculation to establish an effective approach for understanding of the aggregation behavior of MR materials, and thus provides a deep insight into the spectral broadening by resolving the aggregation behaviors of MR emitters.

The ultrasensitive detection of prostate-specific antigen (PSA) remains challenging for therapeutic evaluation and management of prostate cancer, particularly in monitoring post-prostatectomy recurrence. Current immunoassays, however, lack the sensitivity and robustness necessary for detecting trace-level PSA in clinical samples. To address this limitation, we develop a triplet energy transfer (TET)-sensitized downshifting luminescence immunosorbent assay (TET-DLISA) platform by utilizing size-optimized NaGdF₄:Yb³⁺/Er³⁺ downshifting nanoparticles (DSNPs) functionalized with a carboxylated near-infrared dye (Cypate) as signal reporters, for background-free NIR-II detection. Under 808-nm excitation, efficient TET from Cypate to Yb³⁺ amplifies the NIR-II emission of Er³⁺ by 284 times in 5.8-nm DSNPs, achieving a highly enhanced intersystem crossing efficiency (82.8%) while minimizing interfacial energy loss. By introducing DSNP@Cypate as an NIR-II signal reporter, the proposed TET-DLISA enables ultrasensitive PSA quantification via alkaline phosphatase (ALP)-catalyzed phosphate displacement of Cypate, yielding an outstanding signal-to-background ratio (SBR) of 273 and a detection limit of 98 fg mL⁻¹, which is three orders of magnitude more sensitive than the corresponding ALP-based ELISA. Clinical validation with patient sera confirms a strong correlation with the results from commercial kits, demonstrating the platform's clinical utility for post-surgical monitoring. This TET-DLISA platform provides a transformative paradigm for ultrasensitive biomarker detection, addressing unmet needs in precision diagnostics.

Supramolecular macrocyclic hosts, such as crown ethers, cucurbiturils, calixarenes, cyclodextrins, and pillararenes, have significantly advanced host–guest chemistry. However, their practical applications in functional materials are often limited by structural diversity constraints, suboptimal photophysical properties, and inherent nonemissive characteristics. To overcome these limitations, the orthogonal incorporation of aggregation-induced emission-active tetraphenylethene (TPE) units into macrocyclic skeletons has emerged as a promising strategy. This minireview systematically categorizes TPE-embedded macrocyclic hosts into three types, non-, semi-, and full-TPE-embedded, based on the skeleton of TPE integration, highlighting their molecular design principles, photophysical properties, and diverse applications. Drawing upon research advances from the past 5 years, this minireview underscores the dual functionality of conventional macrocyclic skeletons and TPE units, which stems from the restriction of intramolecular rotation mechanism. Furthermore, key challenges in molecular design and potential future research directions are outlined to guide the development of next-generation TPE-based macrocyclic hosts with tailored functionalities, thereby deepening the understanding of structure–property–function relationships.

Nuclease nanozymes promise robust, tailorable alternatives to natural nucleases, but suffer from their limited hydrolytic activity due to the Lewis acidity-centric mechanistic dogma and the unclear role of nanozyme–DNA interactions. Here, we report an affinity-driven strategy that upends conventional cognition. A series of lanthanide metal-organic frameworks (Ln-MOFs) were constructed, with catalytic efficiency decoupled from simple acid strength. Activity increased with the lanthanide atomic number despite a decrease in nanozyme-DNA affinity. Among these, Yb-BDC (terephthalic acid-based) exhibited the highest DNA-cleaving efficiency reported to date (half-life ≈ 30 min), yet showed minimal activity toward the traditional model substrate bis(4-nitrophenyl) phosphate (BNPP), thereby challenging the conventional Lewis acidity-driven paradigm. This unexpected inverse relationship reveals a critical binding-release cycle as the true driver of DNA hydrolysis. Capitalizing on this discovery, we developed a synthetic CRISPR/Cas-inspired biosensing platform by integrating Yb-BDC with rolling circle amplification, replacing natural nucleases. This system enables ultrasensitive detection of non-nucleic acid targets, expanding the scope of nanozymes in diagnostic applications. Our findings not only establish host–guest interaction engineering as a new paradigm for nuclease nanozymes design but also pioneer a modular framework for their application in biosensing technologies.

Photoactivatable peroxynitrite (ONOO⁻), with prolonged half-life, enhanced diffusion, and precise spatiotemporal control, has emerged as a potent anti-biofilm and antimicrobial agent. However, conventional ONOO⁻ generators are usually designed using planar molecular skeletons, which suffer from aggregate-caused reactive oxygen species reduction, thereby restricting ONOO⁻ production. Herein, we present the series of photoactivatable ONOO⁻ generators with aggregation-induced emission (AIE) characteristics—PyTP-NO, PyPTP-NO, and +PyPTP-NO—among which +PyPTP-NO enables efficient ONOO⁻ production. Enhancing electron-withdrawing capability and extending π-conjugation has proven to be an effective strategy for designing ONOO⁻-generating AIEgens, as the resulting increases in excitation coefficients and intersystem crossing promote both superoxide anion generation and nitric oxide (NO) release, thereby boosting ONOO⁻ production. To overcome the biofilm barrier, +PyPTP-NO was further incorporated into the fast-dissolving tips of a bilayer microneedle patch (+PyPTP-NO@DMN) to enable rapid release of the +PyPTP-NO for efficient biofilm eradication, while the base layer was loaded with recombinant collagen (CF-1552) to facilitate wound healing. Post-activation, +PyPTP-NO converts to the non-toxic product +PyPTP-NH, minimizing photo-toxicity to ensure biosafety during wound healing. This study not only provides a generalizable molecular design strategy for developing efficient ONOO⁻ generators but also establishes a versatile therapeutic platform that enables effective biofilm eradication and safe tissue regeneration.

Gliomas present a significant challenge in oncology due to their often subtle early symptoms and the insidious nature of their growth, which is compounded by the blood–brain barrier. Recent evidence has highlighted the diagnostic and therapeutic potential of monocytes, macrophages, and microglia in the context of glioma. This review focused on emerging evidence and hypotheses concerning the components and interrelationships within the mononuclear phagocyte system (MPS) in the central nervous system and its role in glioma development and invasion. By summarizing the involvement of the MPS in glioma biology, this paper offers a novel perspective for the integration of liquid biopsy and targeted therapies in oncology.

Energy dissipation caused by π–π stacking and bond rotation has long hindered the practical application of imine-based covalent organic frameworks (COFs) in the optical field. In this study, we constructed a class of COFs with dual-mode fluorescence emission, overcoming the intrinsically low fluorescence efficiency limitations of imine-based COFs. The non-coplanar linker molecules endow the novel COFs with aggregation-induced emission effects. Furthermore, the enol-keto tautomerism generated during COFs synthesis not only restricted bond rotation but also induced excited-state intramolecular proton transfer, further enhancing fluorescence output. Through the combined action of these two luminescent modes, the obtained imine-based COF-2 and COF-3 exhibited high quantum yields of reaching 10.7% and 13.1%, respectively. The broad photoexcitation range and intense fluorescence emission provide a stable internal reference during detection, reducing signal interference from environmental variations. Combined with the sensitized luminescence produced by rare earth ions on antibiotics, a new ratiometric probe can be constructed to detect trace amounts of antibiotics in water. This work presents a new strategy for designing fluorescent imine-based COFs, promoting their potential application in the field of luminescent sensing.

Stimuli-responsive circularly polarized luminescence (CPL) materials have received extensive attention in the field of information encryption and anti-counterfeiting due to their ability to intelligently respond to external stimuli, enabling dynamic modulation of CPL properties. In this work, chiral luminescent R/S-CsPbBr₃ nanoparticles (NPs) are employed to induce CPL in achiral host lanthanide metal–organic frameworks (Ln-MOFs), thereby achieving the high-performance optical stimuli-responsive CPL. This synthetic strategy demonstrates considerable universality and significantly expands the CPL spectral coverage through rational modulation of Ln-MOFs. The resulting R/S-CsPbBr₃@Eu-MOF composite materials exhibit excellent CPL performance with a luminescence dissymmetry factor (g_lum) as high as 1.3 × 10⁻², attributed to synergistic energy/charge transfer processes mediated by π–π stacking interactions between the host Eu-MOFs and guest R/S-CsPbBr₃. The R/S-CsPbBr₃@Ln-MOF composite materials feature two distinct chiral emission centers, allowing wavelength-programmable CPL emission under different excitation wavelengths. This property holds significant potential for applications in multilevel information encryption and anti-counterfeiting.

Cancer immunotherapy is a groundbreaking treatment that utilizes the body's immune system to fight against cancers. Despite the clinical application of several immunotherapeutic agents, challenges persist, including limited patient responsiveness and adverse events stemming from immune activation, which constrain overall efficacy. Recent advances in aggregation-induced emission luminogens (AIEgens) have propelled innovations in nanomedicine. Traditional fluorophores often suffer from aggregation-caused quenching (ACQ). On the contrary, AIEgens exhibit intense emission upon aggregation, alongside advantageous properties, including minimal background interference, high photostability, as well as multifunctional therapeutic capabilities (such as photothermal therapy, PTT; photodynamic therapy, PDT; and sonodynamic therapy, SDT). Moreover, their exceptional biocompatibility positions them as promising agents for tumor immunotherapy. This review offers a thorough examination of how AIEgens enhance antitumor immunity through mechanisms such as immunogenic cell death (ICD), apoptosis, and pyroptosis, which collectively activate immune cells, reprogram the immunosuppressive tumor microenvironment (TME), suppress tumor proliferation, and mitigate metastasis and recurrence. By highlighting these advances, we aim to stimulate further research into the development of next-generation AIEgens for broader immunological applications and to promote their clinical translation.

A fundamental understanding of catalytic activity and mechanism for electrocatalytic CO₂ reduction reaction (CO₂RR) from a single-metal atom to its monolayer on another metal substrate is crucial for bimetallic catalysts design. Herein, in situ surface-enhanced Raman scattering (SERS) spectroscopy systematically probed electrocatalytic CO₂RR on Au@Pd catalysts with varying Pd coverage, from isolated single-Pd atoms and Pd nanoislands to Pd monolayers on Au surfaces. In situ SERS sensitively detected the adsorption behavior of *CO intermediate, which, combined with electrocatalytic performance, reveals that isolated Pd single atoms on Au show the best activity for CO₂-to-CO conversion and can enhance the activity of nearby Au sites. This is attributed to the moderate energy of *COOH formation and *CO desorption on single-Pd atoms as corroborated by calculations. Moreover, we observed different potential-dependent behavior of *CO adsorbed on Pd nanoisland and monolayer surfaces. Theoretical results suggest that surface *H on Pd reverses the binding energy of *CO(atop) and *CO(bridge) at Pd step edge sites, making *CO(atop) more favorable, whereas *CO(bridge) is more stable without *H adsorption. This reveals the important role of *H in regulating intermediate adsorption configurations during CO₂RR. These observations are valuable for fine-tuning the atomic structure of bimetallic catalysts with suitable *H and *CO absorption properties for high CO₂RR performance.

Engineered RNA devices can identify disease-specific markers and precisely regulate gene expression, which is of great significance to the development of precision medicine. Some studies are shifting the focus from systemic drug delivery to precise gene regulation. A series of targeted delivery technologies has achieved enrichment of RNA drugs in specific tissues/organs. However, the limited cellular selectivity of RNA remains a major obstacle to progress in this field. The cellular precise regulation still requires much improvement. In recent years, advances in synthetic biology have facilitated the development of various RNA devices capable of specifically recognizing intracellular transcripts, proteins, and microRNAs. Nevertheless, the application of these tools remains largely restricted to in vitro cell detection and cell fate manipulation, due to insufficient cross-disciplinary collaboration. Therefore, given the advantages of advanced delivery technologies, combined with the RNA devices that enable precise regulation of gene expression at the cellular level, now is an opportune moment to integrate these RNA devices with state-of-the-art delivery platforms. Such integration promises to enhance the efficacy of engineered RNA devices for precise in vivo targeted therapeutics. In this review, we highlight examples of the advances and current limitations of RNA devices, including toehold switches, microRNAs, and ADAR (adenosine deaminase acting on RNA) sensors for precision disease treatment via advanced delivery systems. These considerations are essential to develop strategies for the targeted therapeutic exploitation of RNA device-based and delivery systems as a powerful programmable biological platform. Furthermore, we will assess the current maturity of RNA device technology and identify emerging innovation areas expected to drive significant future progress.

The rational design of aqueous-phase supramolecular catalysts that integrate substrate recognition, activation, reaction selectivity, and recyclability remains a significant challenge. This work presents a cucurbit[8]uril (Q[8])-based supramolecular photocatalyst, TMV⁸⁺@Q[8], which selectively encapsulates aromatic sulfide substrates via host-stabilized charge transfer (HSCT) interactions while markedly enhancing singlet oxygen (¹O₂) generation. Under visible-light irradiation, the substrate-TMV⁸⁺@Q[8] system facilitates the efficient catalytic oxidation of aromatic sulfides to sulfoxides. Competitive displacement experiments confirm that product desorption is substrate-driven, enabling catalyst regeneration. Crucially, the Q[8] cavity plays a multifaceted role by enhancing substrate activation through HSCT, promoting ¹O₂-mediated oxidation via confinement effects, and enforcing selectivity through size exclusion. These findings establish a new paradigm for supramolecular photocatalysis, wherein macrocyclic confinement concurrently enhances substrate recognition, catalytic efficiency, and recyclability. This study thereby provides a strategic blueprint for designing enzyme-inspired supramolecular photocatalysts operable in aqueous media.

The aggregation of α-synuclein (ɑ-syn) coupled with overexpressed neuroinflammation instigates the degeneration of dopaminergic neurons, thereby aggravating the progression of Parkinson's disease (PD). Herein, we introduced a series of hydrophobic amino acid-based carbon dots (CDs) for inhibiting ɑ-syn aggregation and mitigating the inflammation in PD neurons. Significantly, we show that phenylalanine CDs (Phe-CDs) could strongly bind with ɑ-syn monomers and dimers via hydrophobic force, maintain their stability, and inhibit their further aggregation in situ and in vitro, finally conferring neuroprotection in PD by rescuing synaptic loss, ameliorating mitochondrial dysfunctions, and modulating Ca²⁺ flux. Importantly, Phe-CDs demonstrate the ability to penetrate the blood–brain barrier, significantly improving motor performance in PD mice. Our findings suggest that Phe-CDs hold great promise as a therapeutic agent for PD and the related neurodegenerative disease.