Atomically precise copper sulfide nanoclusters (Cu-S NCs) are of great interest, yet research on their controllable synthesis methods and luminescent properties remains limited. Herein, we report the syntheses and structures of two novel Cu-S NCs: [Cu20S(AT)8(dppm)4(H)8](ClO4)2 (Cu20-H) and [Cu20S3(AT)12(dppm)2](ClO4)2 (Cu20-S), (HAT = 1-adamantanethiol, dppm = bis(diphenylphosphino)methane), with Cu20-S being the first Cu-S NCs prepared via a sulfide-release approach involving thioacetamide. Both clusters exhibit unique structures with regiospecific organic surface coverage: dppm ligands are distributed at both ends of Cu20-H and at one end of Cu20-S. The core of Cu20-H is chiral with D2 symmetry, whereas the core of Cu20-S exhibits only mirror symmetry. Cu20-H is nearly nonemissive, while Cu20-S exhibits orange luminescence with a high photoluminescence quantum yield (PLQY) of 23.54% and a long lifetime of 10.08 μs at room temperature. The boost in the brightness of Cu20-S can be attributed to its rigid and polar structure, which results from the additional sulfide ions. This work presents a novel approach for constructing Cu-S NCs, enriches the copper cluster family, and provides insights into the luminescent properties of Cu-S NCs.

Background: Respiratory syncytial virus (RSV) remains a major cause of acute lower respiratory tract disease, yet current prefusion F (preF)-based RSV vaccines depend on intramuscular injection and cold-chain distribution, limiting broad deployment. Dissolving microneedle array patches (MAPs) offer a minimally invasive, needle-free, and potentially thermostable alternative to conventional vaccine delivery. Methods: We formulated an engineered prefusion-stabilised RSV F antigen (CL073A) into dissolving microneedle array patches. Candidate formulations were screened for antigenicity and mechanical performance. The delivery efficiency, immunogenicity and storage stability were evaluated in BALB/c mice, and protective efficacy was assessed in a cotton rat challenge model. Findings: Following formulation screening, two lead CL073A-loaded MAP formulations (MAPs-CL073A) were identified that preserved antigenicity and mechanical performance and showed prolonged local antigen retention relative to intramuscular injection. In mice, MAPs-CL073A elicited markedly enhanced and durable humoral immunity, inducing approximately five-fold higher neutralizing antibody titers than intramuscular immunization at a ten-fold lower antigen dose, demonstrating a pronounced dose-sparing effect. In cotton rats, MAPs-CL073A conferred robust protection against RSV challenge by reducing lung viral burden and pulmonary pathology, with the 10 μg regimen (F2-MAP) achieving near-complete protection. Furthermore, the patches fully retained antigen bioactivity and in vivo immunogenicity after 6 months of room-temperature storage. Interpretation: Our findings demonstrate antigen delivery is a critical dimension of RSV vaccine performance and support dissolving microneedle delivery as a versatile strategy to enhance both the efficacy and deployability of RSV vaccines.

Abnormal proliferation and dysregulated physiological metabolism of tumors give rise to a unique tumor microenvironment (TME) within tumor tissues. Mounting evidence indicates that a reduction of lactate in TME reverses the immunosuppressive state and enhances the effectiveness of immunotherapy to improve anti-tumor immune responses. Moreover, protein-based photosensitizers are particularly promising, as they can be genetically encoded for precise spatial control and tailored expression in vivo. Herein, we report the development of a complete expression-type self-luminescent bacterial delivery platform, which synergizes protein photosensitizer-driven photodynamic therapy (PDT) with lactate-targeted immunotherapy to achieve enhanced antitumor efficacy. By engineering Escherichia coli Nissle 1917 to function as an internal light source, our integrated strategy facilitates sustained expression and localized activation of self-luminescent photosensitizers at tumor sites, while achieving continuous lactate depletion via stable expression of lactate oxidase within the TME. Together, this dual-action mechanism works to reshape the immunosuppressive TME and potentiate PDT efficacy, as corroborated by the restrained bacterial burdens in non-tumor organs, the significant downregulation of Ki-67, vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) relative to control groups, coupled with unaltered body weight and intact histological structure in non-malignant tissues. Our probiotic-based living drug supports the progress of engineered probiotics as a safe, effective, and patient-friendly alternative to typical PDT against breast cancer.

The pathological crosstalk between endoplasmic reticulum (ER) stress and mitochondria (MT) dysfunction aggravates rheumatoid arthritis (RA) process by promoting the abnormal formation of mitochondria-associated ER membranes (MAMs). Current single organelle-specific therapies are insufficient to halt MAMs-mediated pathological inter-organelle communication and thereby showed limited efficacy in suppressing RA. A two-pronged dual organelles regulatory strategy that concurrently inhibit ER stress and MT dysfunction, thereby suppressing the aberrant MAMs formation will be promising to achieve prolonged RA remission. Due to the multiple delivery barriers from tissue to sub-organelle level, conventional approaches involve decorating nanocarriers with multiple functional groups. However, this typically leads to increased structural complexity and unpredictable in vivo performance. Here, we adopted a minimalist modular design strategy. By fine-tuning the density and ratio of dual organelles-targeted modules, we optimized the physicochemical properties of the Res@DPGT nanoplatform for maximal sub-organelle drug delivery. The optimal two-pronged nanoplatform Res@DPGT achieve a hierarchical targeting process from the tissue level to sub-organelle level, ultimately delivering therapeutic resveratrol (Res) to ER and MT. In inflammatory cells, Res@DPGT significantly suppress ER stress and MT dysfunction by disrupting MAMs formation, eliciting potent anti-inflammatory efficacy. In arthritic rats, intravenously administrated Res@DPGT show enhanced internalization by circulating monocytes and leverage the inflammatory tropism of circulating monocytes to achieve preferential distribution and prolonged retention in inflamed joints. Ultimately, Res@DPGT remarkedly alleviate RA by disrupting the MAMs-mediated pathological ER-MT coupling.

Accurate early screening for hepatocellular carcinoma (HCC) requires multi-target detection methods with high sensitivity and strong anti-interference capability. In this study, we developed an aptamer-mediated SERS sensing method based on bimetallic magnetic nanotubes for the simultaneous detection of HCC markers alpha-fetoprotein (AFP) and Golgi protein 73 (GP73). Tubular Fe3O4 nanostructures were innovatively synthesized as magnetic carriers, onto which a gold-layer, an internal standard molecule (4-mercaptophenylboronic acid), and a silver-layer were sequentially deposited to construct a capture substrate integrating signal calibration and electromagnetic enhancement functions. Raman tags with non-overlapping spectra in the Raman-silent region (1800-2500 cm-1) were screened to establish a sandwich detection system. Using a portable Raman spectrometer and intelligent software, this method achieved rapid quantification of AFP and GP73, with detection limits of 0.433 pg/mL and 0.370 pg/mL, respectively, and recovery rates in spiked serum samples ranging from 95.62% to 106.2%. By simply replacing the aptamers, this method can be readily extended to other targets, demonstrating excellent versatility. This work provides a reliable analytical tool for early HCC diagnosis and establishes a foundation for developing on-site multi-target detection systems for complex samples.

Nanoparticle-targeted formulations are crucial for mitigating the cardiotoxicity, hepatotoxicity, and nephrotoxicity associated with Doxorubicin (Dox) in triple-negative breast cancer (TNBC) treatment. However, nanoparticles are readily recognized and cleared by the immune system, limiting their targeting efficiency. To overcome this limitation, we developed a biomimetic nanodrug delivery system that exploits the elevated cholesterol demand of tumor cells and the immune-evasive properties of endogenous cholesterol. The system employs cholesterol-modified core-shell mesoporous silica (CSMSN) nanoparticles (Chol/Dox-CSMSN), in which Dox is encapsulated within the core and cholesterol coats the exterior. This design enables active targeting through the low-density lipoprotein receptor (LDLR)-mediated cholesterol metabolism pathway, markedly enhancing tumor-specific drug accumulation. Experimental results demonstrated that cellular uptake of Chol/Dox-CSMSN was approximately twofold higher than that of Dox-CSMSN. Following lysosomal uptake, Dox was released in response to glucosylceramidase activity, achieving a cumulative release of 70 % within 48 h. Consequently, the IC50 value for 4T1 cells decreased by 6.07-fold, and cell migration was significantly suppressed, with a scratch migration rate of 15.7 %. Biosafety assessments revealed a hemolysis rate below 5 %, no histopathological abnormalities in major organs, and while blood biomarkers remained comparable to control levels (p > 0.05). This biomimetic nanodelivery platform, leveraging endogenous metabolic pathways for targeted drug transport, provides a promising strategy for safe, efficient and low-toxicity chemotherapy.

The increasing challenge of antibiotic resistance necessitates the development of novel antibacterial strategies. In this study, a novel kind of self-capped carbon dots is synthesized from methylene blue (MB) and cetyltrimethylammonium chloride (CTAC), and named as MC-CDs that are specifically designed for enhanced photodynamic antibacterial activity. Under 660 nm laser irradiation, MC-CDs demonstrate high inactivation rates of Escherichia coli (96.83%) and Staphylococcus aureus (94.44%) at 14 and 18 µg mL-1 effectively, disrupting bacterial cell membranes. The incorporation of zinc cations (Zn2+) doping further enhances the antibacterial potential of MC-CDs, enabling substantial efficacy even in the absence of light due to improved electrostatic interactions with bacterial membranes. In comparison to commercial agents such as salicylic acid, p-chloro-m-xylenol, and triclosan, Zn@MC-CDs exhibit superior antibacterial performance. When formulated into a hand sanitizer, Zn@MC-CDs maintained over 90% efficacy, displaying excellent stability and extremely low cytotoxicity, highlighting their potential for safe and effective use in personal hygiene products. This study introduces self-capped carbon dot as a promising antibacterial agent, addressing a critical need for advanced and reliable solutions in infection control.

Nanozymes capable of generating efficient reactive oxygen species (ROS) and disrupting redox homeostasis at the tumor microenvironment (TME) have attracted tremendous interest. However, the strategy to endow multi- catalytic functions in one nanozyme and disclose their catalytic active sites for tumor treatment remains challenging. Herein, monodispersed ReSe2 nanoflowers with expanded-interlayer spacing were successfully synthesized with hexa-enzymatic activities, including catalase (CAT), oxidase (OXD), superoxide dismutase (SOD), peroxidase (POD), nicotinamide adenine dinucleotide (NADH) oxidase (NOX) and glutathione peroxidase (GPx), which can continuously boost ROS generation in a "self-cycling" way and overwhelm the antioxidation defense from TME. As confirmed by experimental and density functional theory (DFT) calculation results, the expansion of the interlayer spacing provides solid evidence for explaining their high redox catalytic activities. It simultaneously caused mitochondrial dysfunction and adenosine triphosphate (ATP) depletion via disrupting NADH/ NAD+ balance. With the combination of eminent photothermal conversion efficiency (PCE, 65.2 %) in the near- infrared (NIR) biological window, ReSe2 nanozymes not only exhibit outstanding therapeutic effects but also perform as excellent photoacoustic (PA) imaging agents in vivo. To the best of our knowledge, this is the first paragon for the biomedical application of ReSe2 nanoplatform and transition metal dichalcogenide-based nanozymes with expanded interlayer spacing in synergistic oncotherapy.

Microneedles represent a miniaturized mechanical structure with versatile applications, including transdermal drug delivery, vaccination, body-fluid extraction, and bio-sensing. Over the past two decades, microneedle-based devices have garnered considerable attention in the biomedicine field, exhibiting the potential for mitigating patient discomfort, enhancing treatment adherence, avoiding first-pass effects, and facilitating precise therapeutic interventions. As an application-oriented technology, the innovation of microneedles is generally carried out in response to a specific demand. Currently, three most common applications of microneedles are drug delivery, fluid extraction, and bio-sensing. This review focuses on the progress in the materials, fabrication techniques, and design of microneedles in recent years. On this basis, the progress and innovation of microneedles in the current research stage are introduced in terms of their three main applications.

Microneedle array-based drug delivery offers a minimally invasive and safe approach for breaching the skin barrier, enabling localized and targeted treatment-an advantage particularly valuable in chronic condition management, such as rheumatoid arthritis (RA). RA presents a multifaceted pathophysiology, often necessitating long-term pharmacological management. However, conventional oral administration may lead to systemic drug distribution, increasing the likelihood of adverse effects, and ultimately undermining therapeutic efficacy. In this study, a hollow microneedle array was employed for effective delivery of Tofacitinib and the antioxidant N-acetylcysteine (NAC). A comprehensive evaluation was conducted across multiple levels, in which inflammation and cartilage degradation were assessed histologically using hematoxylin-eosin (H&E) and Safranin O-Fast Green staining. Radiologically, micro-computed tomography (micro-CT) was employed to visualize bone structure alterations. On the molecular level, enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokines and oxidative stress markers. Furthermore, differentially expressed genes and enriched signaling pathways were identified through transcriptomic profiling pre- and post-treatment. And the potential regulatory targets and mechanistic insights into the therapeutic response were elucidated through correlation analyses between gene expression profiles and pathological indicators. This study provides a mechanistic and computational basis for precision targeted therapy, validates the efficacy and safety of microneedle delivery in a rheumatoid arthritis (RA) model, and demonstrates its potential application in local drug delivery strategies.

Carbon dots (CDs), as emerging zero-dimensional carbon-based nanomaterials, demonstrate immense potential across optical displays, bioimaging, chemical sensing, information anti-counterfeiting, and optoelectronic devices. This promise stems from their exceptional tunable photoluminescence, low toxicity, biocompatibility, and abundant raw material sources. Since their discovery, research has centered on resolving controversies regarding classification, formation mechanism, microstructure, and luminescence principles while achieving controllable optoelectronic properties. Applications have evolved from basic fluorescent labeling to advanced domains including multimodal theranostics, high-sensitivity (bio/chemical) sensing, stable optoelectronic devices, intelligent anti-counterfeiting systems, and environmental/energy catalysis. Future challenges demand breakthroughs in structural homogeneity/scalable eco-fabrication, universal structure-opto/electronic-property models, stability/efficiency in complex environments, and multifunctional synergy (e.g., photo-electro-catalysis). This comprehensive review systematically examines milestone advances in CDs research over the past decade—spanning synthesis methodologies, photo/electronic property modulation mechanisms, and innovative applications—while dissecting key challenges and envisioning future pathways as versatile intelligent nano-platforms.

Phosphorescent materials have potential applications in anticounterfeiting and optoelectronics, but their luminescence is generally quenched at elevated temperatures. Herein, a synergistic locking strategy has been developed to achieve high-temperature phosphorescence (HTP) of carbon dot (CD) composites. Impressively, the CD composites retain over 90% and 75% of their phosphorescence intensity at temperatures up to 110 and 170 °C, respectively. Even at temperatures higher than 170 °C, the phosphorescence persists for 5 s, demonstrating remarkable stabilization of triplet excitons. Experimental and theoretical results revealed that this outstanding thermal resistance stems from the synergistic locking effect of interlayer covalent bridges and multiple hydrogen bonding at the interface. Furthermore, by adjusting the degree of graphitization, multicolor HTP ranging from blue to red has been achieved for the CD composites. This work not only provides a facile and versatile way to construct multicolor CD-based HTP materials but also expands their potential applications in heat-resistant display at high-temperature environments.

Nanozymes capable of inducing metabolic reprogramming and activating the immune response without external stimuli in vivo are highly pursued for malignant tumor therapy. In this paper, a PtIrFeMoZn high-entropy alloy (HEA) nanozyme is designed and synthesized via a simple one-step hydrothermal method. The HEA nanozymes not only trigger apoptosis and ferroptosis via cascade biocatalysis, thereby enhancing immunogenicity, but also enhance the immune effect by targeting the glycolytic pathway. It is worth mentioning that a simple pre-treatment of nanozymes by alternating current (AC) yielded much better therapeutic and immuno-effect. The 'AC-treated' nanozymes exhibit an excellent synergy of peroxidase-like (POD-like), myeloperoxidase-like (MPO-like), and glutathione peroxidase-like (GPx-like) activities, generating a sufficient reactive oxygen species (ROS) storm. Additionally, two immune pathways (ICD and the cGAS-STING) are activated simultaneously. Furthermore, the production of HClO and the depletion of NADH can regulate metabolism, further disrupting the equilibrium of the glycolysis process. This not only increases the cell death but also enhances the immune response in female tumor-bearing mice. This study proposes a multi-pronged therapeutic strategy that can significantly activate anti-tumor immunotherapeutic effects through ROS storm, GSH/NADH oxidation, and lactate/ATP depletion, triggering apoptosis/ferroptosis/immunotherapy. These findings hold significant promise for inspiring the development of HEA nanozymes for tumor immunotherapy.

Objective: Radiation-induced lung damage (RILD) is a critical complication in breast cancer patients undergoing radiotherapy. This study proposes a multi-modal predictive framework integrating dosiomics, radiomics, deep learning-based features, and clinical data to enhance early detection and risk stratification of Grade >= 2 RILD, ultimately supporting personalized radiotherapy planning. Materials and methods: A dataset of 450 breast cancer patients receiving radiotherapy was analyzed, incorporating high-resolution CT scans, 3D spatial dose distributions, and comprehensive clinical parameters such as age, BMI, tumor laterality, chemotherapy regimens, and comorbidities. Imaging data were standardized through voxel resampling and intensity normalization, and features were extracted from both radiomics (215 features) and dosiomics. Mutual Information (MI)-based feature selection was applied to enhance model performance, while a 3D autoencoder with attention mechanisms was utilized to capture spatial and structural patterns linked to RILD. Five-fold cross-validation was performed to ensure robustness. Results: The Intraclass Correlation Coefficient (ICC) analysis identified the most reproducible radiomics features, leading to significant feature reduction while maintaining predictive stability. Multi-modal data integration significantly improved classification performance, with the Voting Classifier achieving 95.89% accuracy and 96.98% sensitivity when using MI-based feature selection. Deep features demonstrated superior predictive power compared to standalone dosimetric data. The 3D autoencoder model with attention mechanisms further enhanced predictive accuracy, achieving 95% accuracy, 0.96 AUC, and 0.93 sensitivity. Conclusion: The proposed multi-modal AI-driven approach effectively predicts Grade >= 2 RILD, addressing limitations of traditional dose-volume metrics. The integration of radiomics, dosiomics, deep learning, and clinical data enhances model accuracy and interpretability, paving the way for personalized risk assessment and optimized radiotherapy planning. Future research should focus on external validation and real-time clinical implementation to further refine predictive capabilities.

Ocular tissues are subject to heightened oxidative stress due to prolonged environmental exposure and intrinsic metabolic radical generation. Although fruits such as cherry tomatoes are rich in natural antioxidants, their poor bioavailability and low stability limit clinical utility. To address this, we developed amphiphilic carbon dots (TM-CDs) via a microwave-assisted synthesis using fresh cherry tomato juice as the single source. The resulting TM-CDs exhibit bright fluorescence, high stability, excellent biocompatibility, multienzyme-like activity, and potent free radical scavenging capacity. Notably, TM-CDs showed significant ocular accumulation in zebrafish, enabling efficient scavenging of diverse ROS species and the mitigation of oxidative damage. Experimental results indicated that TM-CDs not only ameliorated ocular dysplasia in zebrafish induced by cysteamine hydrochloride but also maintained ocular redox homeostasis by upregulating superoxide dismutase (SOD) activity and glutathione (GSH) content, while reducing malondialdehyde (MDA) content. Consequently, the visual behavior of zebrafish, such as the mirror-biting duration, returns to normal. This coordinated multimechanistic recovery highlights the potential of biomass-derived carbon dots as a next-generation nanotherapeutic strategy for oxidative ocular disorders.

ABSTRACTCopper sulfide nanoparticles (CuS NPs) is a promising and efficient photothermal agent, which is widely utilized for cancer therapy. Thus, hyperstable CuS NPs with strong absorbance in second near infrared (NIR‐II) biowindow were prepared by solvent thermal method, which demonstrated good stability and biocompatibility, with deeper tissue penetration of NIR‐II light for photothermal therapy in comparison to that of first near infrared (NIR‐I) biowindow. Subsequently, CuS@Hydrogel was constructed by incorporation of CuS NPs in Ca2+ ions crosslinked sodium alginate to form three‐dimension hydrogel. CuS NPs are homogeneously dispersed in CuS@Hydrogel nanocomposite with the advantages of good photothermal properties and low toxicity. CuS@Hydrogel can effectively treat postoperative melanoma with wound healing ability through the function of photothermal effect. The photo‐induced thermal effect can efficaciously contribute to the elimination of residual tumor tissue. Furthermore, the hydrogel composite can also accelerate to cure the wound of mice due to the surgical removal of tumor. This novel biofunctional hydrogel platform can provide a significant candidate for the inhibition of local tumor recurrence and skin regeneration after surgical treatment of melanoma.

Ultra-sensitive nucleic acid detection is important for rapid prevention of infectious diseases. Recently, clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) systems with great target specificity and programmability have demonstrated amazing capabilities in the field of nucleic acid detection. However, most CRISPR/Cas systems-based strategies still rely on pre-amplification of nucleic acid, which limits their clinical application in point of care detection. Here, we designed a novel electrochemical CRISPR/Cas biosensor (called E-Sb CRISPR) that utilizes antimonene nanosheets (Sb NSs) modifications. Due to the strong interaction between Sb NSs and single stranded DNA (ssDNA), E-Sb CRISPR exhibited specific nucleic acid detection capabilities with a detection limit of 100 aM within 35 min. Notably, the sensor showed excellent selectivity to target DNA in serum in the presence of nucleus acid extracted from other viruses. The excellent stability (8 weeks) and reproducibility (50 cycles) of this sensor were observed. By developing microcircuits and software systems, rapid acquisition of detection results on mobile electronic devices is possible. Therefore, the E-Sb CRISPR showed great promise as a scalable nucleic acid detection platform for early diagnosis.

Fluoride contamination has become a worldwide concern since it can cause serious environmental problems. Zirconium-based adsorbents exhibit satisfactory fluoride removal capabilities. However, their narrow pH applicability, tendency to aggregate, and difficulty in separation hinder practical applications. Herein, a high efficiency hydrous ZrO2 polypyrrole nanocomposite (HZrO2@PPy) was prepared by in-situ oxidative polymerization. The results indicate that HZrO2@PPy exhibit optimal fluoride (F-) removal efficiency in a wide pH range (3-10), with good anti-interference performance to coexisting anions (Cl- , HSO4- and SO42-). The adsorption kinetics conformed to the quasi-second-order model and the adsorption process could reach equilibrium within 10 min. The adsorption isotherms are in good agreement with the Langmuir model, and the maximum adsorption capacity of F- at neutral pH could be 63.61 mg/g. Thermodynamic analysis shows that the adsorption defluorination of HZrO2@PPy is a spontaneous, endothermic, entropy-reducing reaction. In addition, the adsorption mechanism was investigated based on XPS and FTIR analyses. The results demonstrate that the electrostatic attraction, complexation effect and ion exchange are the main mechanisms for the adsorption of Fon HZrO2@PPy. The results presented in this work indicate the potential of the developed nanocomposite as a defluoridation material for environmental water.

Exhaled breath-based disease diagnosis is an ancient technique, and the application of this technique is rapidly developing for disease quick testing, such as viral infection, asthma, chronic kidney disease, and so on. Among the diagnostic tools, an exhaled breath-based test has demonstrated the merits of being non-invasive, convenient, quick, and comfortable. In this review, the exhaled breath diagnosis via the gaseous part of the breath is the major focus. First, the summary of state-of-art studies based on exhaled gas detection is described. Second, typical disease-related exhaled gas and their measurements are described. Finally, the various structure of field effect transistor (FET)-type sensors for gas-based disease detection is discussed in detail. This review may inspire new research ideas and directions for applying FET-type sensors to quick disease detection via the gaseous route. Exhaled gas-based disease diagnosis is so appealing because it is noninvasive, convenient, and easy to accept. The development of FET-type gas sensors with different structures (Back-gate FET, top-gate FET, HEMT, floating-gate FET, and multiple-gate FET) is expected to promote the popularization of this diagnostic method and provide strong support for the early detection and treatment of diseases.image