Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease without cure. Reactive oxygen species (ROS)-induced oxidative stress and mitochondrial dysfunction are considered critical factors in ALS pathogenesis. Here, we design carbon dot superoxide dismutase (SOD) nanozymes with manganese doping (Mn@CDs) by screening for the optimal active site according to the special structures of natural SODs. Mn coordinates with N and O in the CD scaffold, optimizing its structure, enhancing electron transfer and superoxide anion binding, and achieving superhigh specific activity of more than 7×10 4 U/mg. Theoretical calculations reveal the SOD-like activity of Mn@CDs from both kinetic and thermodynamic perspectives, identifying MnN 2 O 2 (with amide-derived N) as the most likely active center. Unlike previous single-atom nanozymes with planar structures, this active center exhibits a coordination environment and a non-planar spatial conformation that closely resembles the active site of natural MnSOD enzymes. After being applied in ALS therapy, Mn@CDs effectively prevent oxidative stress and protect mitochondria from abnormalities in morphology, quantity, and function. Hence, administration of Mn@CDs prolonged survival by 14.5 days, with a 93% increase over the effect of edaravone. These results suggest that Mn@CDs hold significant potential as a promising therapeutic candidate for ALS treatment.

Controlling the internal architecture and morphology of lipid nanoparticles (LNPs) beyond their size remains a central challenge in nanoparticle engineering. Conventional micromixer-based assembly methods provide rapid mixing but lack the temporal resolution to manipulate the multiple competing kinetic processes that occur during LNP self-assembly. Here, we demonstrate kinetically controlled fabrication of Janus-structured surface nanobubble-lipid nanoparticles (SNB-LNPs) using an ultrasonic micromixer that enables independent tuning of three critical time scales: mixing time (t m), bubble generation time (t b), and LNP self-assembly time (t a). By systematically mapping these time scales, we establish an assembly kinetic zone diagram that defines the process windows for distinct nanoparticle architectures, including spherical LNPs, bleb LNPs, and the previously inaccessible SNB-LNPs. Cryogenic transmission electron microscopy and small-angle neutron scattering confirm the Janus morphology of SNB-LNPs, featuring a gas-filled nanobubble compartment (∼17 vol % gas phase) attached to a lipid-mRNA core. The assembly outcome can be further modulated by gas supersaturation and lipid shell composition, providing additional degrees of freedom for structural control. As a proof of concept, the ultrasound-responsive SNB-LNPs demonstrate enhanced mRNA delivery both in vitro and in vivo. This work establishes a process engineering framework for fabricating multicompartment nanoparticles with nonequilibrium architectures through kinetic control in continuous-flow microreactors.

When nanoparticles (NPs) enter biological environments, they are rapidly coated by biomolecules, forming the protein corona (PC) that defines their biological identity and dictates how NPs are recognized, distributed, and processed by living systems. Capturing the authentic features of the PC demands experimental conditions that preserve its native state, which are difficult to achieve once NPs are removed from their biological milieu. Despite significant progress, current PC quantification methods still rely on separating the NP-PC complex from its native environment, thereby compromising the corona's integrity and preventing accurate evaluation of its physicochemical properties. Here, we introduce a fractionation-free approach based on synchrotron small-angle X-ray scattering (SAXS) to quantitatively determine the amount of protein adsorbed onto silica NPs under native conditions. By modeling the scattering contribution of free versus bound proteins, we directly extracted the adsorbed mass in both single-protein (serum albumin) and complex proteomic (human serum) systems. The resulting adsorption isotherms enabled the determination of thermodynamic parameters, distinguishing between simple monolayer-like and more complex adsorption regimes. Together, these findings establish SAXS as a non-invasive and quantitative technique for probing the PC in situ without perturbing equilibrium, advancing SAXS toward quantitative PC characterization.

The pursuit of simple yet high-performance materials is important for advancing organic photovoltaics, though structurally simple polymer donors typically underperform. This study reveals precise control over polymer aggregation and donor-acceptor compatibility is key to optimizing active layer morphology. We design three linear conjugated polymers with systematically chlorinated backbones to finely modulate aggregation tendency and surface tension. This strategy concurrently regulates film-formation kinetics and donor-acceptor compatibility. PTTz-Cl50 exhibits ideal aggregation and optimal compatibility with BTP-eC9, enabling sequential deposition that forms a bicontinuous interpenetrating network with appropriate domain size and marked phase purity. This microstructure provides sufficient interfacial area for exciton dissociation while retaining high-purity charge transport pathways. Consequently, the device demonstrates rapid exciton dissociation, efficient charge transport, and suppressed recombination, enhancing both short-circuit current and fill factor. This yield a high power conversion efficiency of 20.42% for linear conjugated polymers, underscoring the promise of low-cost materials for efficient devices.

This study established an ionic liquid-based ultrasound-assisted extraction (IL-UAE) method coupled with UHPLC-MS/MS to extract and quantify five platycodin saponins from Platycodon grandiflorum. We optimized the extraction conditions using single-factor experiments and a Box-Behnken design (BBD) with response surface methodology. The optimal parameters were 0.8 mol/L [C₄MIM][Br], a liquid-to-solid ratio of 43 mL/g, a 38 °C extraction temperature, a 40 min extraction time, and a 6% NaOH concentration. These conditions yielded a total saponin content of 3.184%. The UHPLC-MS/MS method showed strong linearity (R² > 0.9993) and reliability, with recoveries ranging from 87.80% to 114.78%. Furthermore, density functional theory (DFT) calculations (including electrostatic potential, independent gradient model based on Hirshfeld partition, and frontier molecular orbital analysis) were applied to clarify the extraction mechanism. DFT results suggested a possible synergistic interaction pattern: Br⁻ contributed to charge redistribution and hydrogen-bonding interactions with platycodin D, while [C₄MIM]⁺ provided a relatively stable solvation environment. The IL-UAE method demonstrated higher extraction efficiency than conventional water and 70% methanol extractions. Multi-metric greenness assessments, highlighted by an AGREE score of 0.8, showed a favorable greenness profile for the proposed protocol. This work provides an efficient and theoretically supported workflow for the extraction and quality control of platycodin saponins in botanical materials.

The development of broad-spectrum antiviral agents and effective vaccine adjuvants remains a critical challenge. Herein, we report biodegradable CuInP2S6 (CIPS) nanosheets as a dual-functional material that enables direct viral interception and potent immunoenhancement. Its action stems from a functional paradigm we term CIPS-dependent cellular phagocytosis, wherein CIPS binds viral particles and leverages intrinsic phagocytic clearance to promote macrophage-mediated viral uptake and degradation. This process not only directly neutralizes viruses but also enhances antigen presentation and facilitates dendritic cell activation, thereby establishing the foundation for its adjuvant function. Consequently, in a murine immunization model, the CIPS-adjuvanted formulation elicited a significantly stronger humoral immune response, including elevated antigen-specific IgG titers and robust neutralizing antibody induction, even with a monomeric receptor-binding domain antigen. This work elucidates how the antiviral mechanism of CIPS translates into potent immunoenhancement, offering a novel strategy for applying functional nanomaterials in vaccine development.

Nano‑copper oxide (CuO NPs), as a highly promising antibacterial agent in aquaculture, has demonstrated excellent performance against pathogens affecting cultured organisms. However, its application is accompanied by potential toxicity risks to both the cultured organisms and the entire aquatic ecosystem. In this study, CuO NPs was synthesised using a sodium hypophosphite liquid-phase reduction method, and then a toxicity experiment was conducted using 50 μg/L CuO NPs in M. galloprovincialis. Multiple endpoints at Cu distribution, enzyme activity, lipid peroxidation degree, immune-related gene expression, tissue pathology, and metabolic response were assessed in response to CuO NPs exposure. The multi-biomarker approach revealed that CuO NPs toxicity in M. galloprovincialis operated through a coordinated network of effects: tissue-specific Cu accumulation drives histopathological damage, oxidative stress, immune disruption and ultimately systemic metabolic reprogramming. At the metabolomic level, CuO NPs exposure induced a two-system metabolic shift in M. galloprovincialis, featuring lipid upregulation and amino acid downregulation, and six metabolites (three oxylipins up, three amino acids down) that highlighted their potential as sensitive biomarkers for nanomaterial contamination. These molecular-level alterations eventually led to pathological changes in the hepatopancreas and gills. The study could provide a theoretical basis for the toxicity assessment of nanomaterials in bivalves and offer effective support for environmental risk assessments.

The experiment aimed to investigate the potential mechanism of Portulaca oleracea polysaccharide (POL-P) in preventing and treating enterotoxigenic Escherichia coli (ETEC) infection using network pharmacology and molecular docking technology. The active components of POL-P and their corresponding targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PubChem database, and SwissTargetPrediction database. ETEC disease targets were screened using the GeneCards database and Online Mendelian Inheritance in Man (OMIM) database, and intersection targets were identified by constructing a Venn diagram. A protein-protein interaction (PPI) network was constructed using the STRING database to screen core targets. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID database, and molecular docking validation was conducted using AutoDock Vina. The results showed that the active components of POL-P included galactose (Gal), arabinose (Ara), rhamnose (Rha), glucose (Glc), mannose (Man), galacturonic acid (GalA), and glucuronic acid (GlcA), with a total of 15 key targets related to ETEC being screened. 10 core targets, including Toll-like receptor 4 (TLR4), nuclear factor κB subunit 1 (NFKB1), and mitogen-activated protein kinase 1 (MAPK1), were identified through PPI network analysis. GO functional annotation involved 83 biological process terms, 21 cellular component terms, and 18 molecular function terms. KEGG enrichment analysis yielded 86 signaling pathways, primarily including the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, chemokine signaling pathway, T-helper cell 17 (Th17) cell differentiation, and phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt) signaling pathway. Molecular docking results showed that the active components could spontaneously bind to the core target proteins, with binding energies ranging from -8.4 to -3.4 kcal/mol. The study indicates that POL-P exerts its preventive and therapeutic effects against ETEC infection by acting on targets such as TLR4, NFKB1, and MAPK1, and synergistically regulating multiple pathways including inflammatory responses and immune modulation.

Copper is an essential trace element that supports mitochondrial respiration, antioxidant defense, and a range of metabolic pathways, however, its concentration must be tightly regulated to avoid proteotoxicity and organ dysfunction. Disruptions in copper homeostasis-such as those observed in Wilson disease, Menkes disease, and several neurodegenerative disorders-highlight the delicate boundary between copper's physiological roles and its toxicity. Recent advances in nanotechnology have enabled the development of copper-based nanomaterials (CuBNMs) as versatile tools for probing and modulating copper biology in vivo. Owing to their tunable physicochemical properties and organ-selective biodistribution allow precise manipulation of copper localization, redox activity, and stress responses. Mechanistically, the recent discovery of cuproptosis, a regulated cell death pathway triggered by mitochondrial copper overload, has opened new therapeutic opportunities for targeting cancer metabolism. Concurrently, synchrotron-based imaging and spectroscopy techniques now permit direct visualization of copper speciation and nanomaterial transformation within complex tissues, offering insights previously unattainable. This review integrates current perspectives on copper dysregulation with emerging principles governing the design, behavior, and function of CuBNMs, highlighting their potential to correct copper imbalance and to inform next generation copper-based therapeutics.

Carbon dots (CDs), as small zero-dimensional carbon-based nanomaterials, exhibit remarkable optical properties, high biocompatibility, and minimal toxicity. Their surfaces can be readily functionalized, enabling efficient drug loading, targeted modification, and stimulus-responsive release. CDs possess the unique capability to integrate both diagnostic and therapeutic functions, making them ideal carriers for the development of “theranostic” platforms. This paper systematically reviews recent research advances in CDs for tumor therapy, focusing on their mechanisms of action and potential applications as drug delivery systems, photothermal, photodynamic, and multimodal synergistic therapeutic platforms. At the same time, this paper also conducts an in-depth analysis of the challenges and limitations currently facing this field, including key issues such as biosafety, in vivo pharmacokinetics, large-scale synthesis standardization, and tumor microenvironment (TME) barriers. These advances represent a significant progression from fundamental research toward clinical translation.

Upon exposure to biological fluids, nanomaterials rapidly acquire dynamic layers of adsorbed proteins called the protein corona, redefining the biological identity of nanomaterials and governing their in vivo fate. While corona composition has been extensively profiled, two aspects remain poorly understood: dynamic evolution and the receptor-mediated mechanisms underlying its cellular recognition. Here we present a broadly applicable, real-time biosensor-based protocol. This workflow characterizes nanomaterial-protein interactions and identifies cell membrane receptors involved in corona recognition. The protocol distinguishes between soft corona, hard corona, and total corona layers. It can not only quantify dynamic and competitive interactions but also map receptor-corona and receptor-plasma protein interactions using a label-free biosensor-based platform. This method combines biolayer interferometry, or alternatively surface plasmon resonance, or magnetic isolation, with downstream proteomics. It enables functional dissection of the nano-bio interface and provides insights into how corona dynamics govern cellular uptake. The method is compatible with diverse nanomaterial types and biofluids, depending on the experimental scope. The protocol is designed for users with basic experience in areas such as nanotechnology, molecular interaction analysis, proteomic profiling, cell culture, and biofluid sample preparation. The entire process takes ~10 days to complete.

The lack of tumor-specific targeting remains a major bottleneck in photothermal therapy. Here, we exploit the natural affinity of nicotinamide (NAM) for Ki67, a tumor proliferation marker, to design a targeted photothermal nanomaterial. NAM-derived carbon dots (NAM-CDs) were synthesized via a one-step solvothermal method, in which the carbon core serves as a scaffold for the multivalent presentation of NAM moieties. Dynamic molecular docking simulations revealed that NAM-CDs exhibited a markedly enhanced binding affinity toward Ki67, with binding energy of -7.7 kcal/molcompared with -3.8 kcal/mol for free NAM. These results indicate that the multivalent display of NAM not only preserves but also amplifies its intrinsic Ki67-targeting capability. To further optimize the photophysical properties of NAM-CDs, the synthesis temperature was systematically tuned. At 180 °C, the resulting NAM-CDs developed a pyridine-rich surface characterized by maximized pyrrolic-N content and enhanced amide bond formation, facilitating efficient energy transfer from the carbon core to surface states. This optimized electronic structure synergistically enhanced both red fluorescence emission and photothermal conversion efficiency. The pyridine-rich NAM-CDs exhibited excellent biocompatibility, specific nuclear retention through Ki67-mediated interactions in cancer cells, and potent photothermal tumor ablation upon 660 nm laser irradiation in vivo, achieving complete tumor regression without recurrence over a 30-day observation period. By harnessing the inherent Ki67 affinity of NAM, this work provides a facile strategy for imparting tumor-targeting capability to photothermal agents, opening a new avenue for proliferation-marker-directed cancer therapy.

The formation of a protein corona (PC) on the surface of nanoparticles (NPs) in biological environments is a critical factor influencing the fate and functionality of NPs in vivo. This biolayer affects NPs' biodistribution, immune recognition, cellular uptake, and therapeutic efficacy, making it essential for the rational design of nanomedicines. However, traditional analytical techniques often disrupt the native state of the PC, particularly its loosely bound soft corona (SC), leading to incomplete characterizations. In situ analysis methods offer a more accurate representation of PC composition, structure, and dynamics by preserving its native biological context. This review highlights critical advances in in situ PC analysis techniques, including methods for composition identification, structural visualization, and monitoring the dynamic evolution of the PC. It emphasizes the importance of real-time, non-disruptive analysis to better understand the nano-bio interface and its implications for nanomedicine design and safety. Additionally, it discusses challenges in current PC analysis methodologies and proposes future research directions to improve in situ characterization accuracy and standardization.

As a considered potential cathode material for aqueous zinc ion batteries (AZIB), MnO2 has been plagued by poor conductivity, poor cycle stability and structural instability, which hinder its further development. Herein, the electrochemical performances of MnO2 were improved by introducing abundant oxygen vacancies and sulfur doping (denoted as S/VO-MnO2). When the current density is 300 mA g-1 and 1000 mA g-1, the S/VO-MnO2 can still maintain the capacity of 380 mAh g-1 after 400 cycles and 237 mAh g- 1 after 1080 cycles, respectively. The battery capacity decreases gradually and the capacity retention rate can reach 92.23 % at 300 mA g- 1 . Ex-situ XRD and SEM further demonstrated that MnO2 did not manifest any visible structural dissolution during the cycle, and the composite electrode showed good structural stability during the whole cycle.

Nanoparticles (NPs) in biological environments rapidly become coated with a dynamic biomolecular layer known as the protein corona (PC), significantly influencing their biological identity and functionality. Traditional methods used to characterize the PC often disrupt its native state, limiting accurate insights into its true structural and compositional complexity. Synchrotron-based small-angle X-ray scattering (SAXS) provides a powerful alternative, enabling nondestructive, label-free, and in-solution analysis of the PC under physiologically relevant conditions. This minireview critically examines recent advancements in applying SAXS to decode the PC, highlighting methodological developments and exemplary studies demonstrating SAXS's unique ability to resolve interactions at the nano-bio interface. By discussing novel analytical frameworks, such as integrating SAXS with complementary techniques like small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM), we provide a comprehensive overview on the structural and thermodynamic features of the PC. Furthermore, we outline future opportunities including time-resolved SAXS to elucidate the kinetics of corona formation and the establishment of standardized protocols to enhance reproducibility and reliability. Ultimately, this review positions SAXS as an indispensable tool for advancing our understanding of nanoparticle-protein interactions and fostering innovation in nanomedicine.

Effective delivery of lipid nanoparticles (LNPs) and their organ- or cell-type targeting are paramount for therapeutic success. Achieving this requires a comprehensive understanding of protein corona dynamics and the identification of cell receptors involved in the recognition and uptake of LNPs. We introduce a simple, fast, and in situ strategy by a biosensor-based "Fishing" method to uncover protein corona formation on LNPs and identify key receptors of human blood cells that are responsible for the recognition and binding of human plasma corona on the surface of LNPs. Unexpectedly, we observed a significant presence of immunoglobulins with high abundance, especially anti-PEG antibodies, within the LNP corona. These antibodies, along with complement opsonization, drive colony-stimulating factor 2 receptor β (CSF2RB)-mediated phagocytosis by human myeloid cells. These compositions of the human plasma corona and their interactions with neighboring proteins are critical for the recognition and binding of LNPs by cell receptors and cellular uptake. Our findings highlight the pivotal role of anti-PEG antibodies in the circulation and phagocytosis of LNPs in vivo. This approach offers profound insights into nanomaterial behavior in vivo, paving the way for the enhanced design and efficacy of LNP-based therapies.

Nanoplastics are increasingly detected in human tissues, yet their biological interactions and health effects remain poorly understood. Here, we show that polyvinyl chloride (PVC) nanoplastics change lipid metabolism of macrophages such as the induced formation of foam cells through a lipoprotein-mediated mechanism. Using transmission electron microscope, scattering light-confocal imaging, and soft X-ray nano-computed tomography, we visualize intracellular PVC nanoplastics and extensive lipid droplet accumulation in macrophages. Proteomic profiling reveals that PVC nanoplastics acquire apolipoproteins enriched protein corona, particularly ApoA1, imparting them with a lipoprotein-like identity. In response, macrophages selectively upregulate scavenger receptor class B type 1 (SR-B1), a key high density lipoprotein (HDL) receptor involved in cholesterol uptake and lipid homeostasis. These findings uncover a receptor-specific pathway by which apolipoprotein-coated nanoplastics mimic endogenous lipoproteins, disrupt lipid metabolism, and drive foam cell-like transformation. This work highlights uncovered links of the exposure of nanoplastics to cardiovascular risk through metabolic reprogramming.

The treatment of malignant tumors such as melanoma has always been a world-class problem. Single-modality therapy for melanoma is often faced with a balance of therapeutic outcomes and side effects. Combination of multi-modality could greatly improve therapeutic effect without introducing side effects. Herein, the thermal responsive phase change materials (PCM) are utilized to incorporate ultrasmall copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), which were furtherly coated with hyaluronic acid (HA) via strong host-guest interaction between β-cyclodextrin (CD) and ferrocene (Fc), for on-demand combined chemo, chemo-dynamic and photothermal therapy. The supramolecular nanomedicines could accumulate at tumor site owing to HA coating upon intravenous injection, and PCM would melt to release CuS NPs, DOX as well as Fc under NIR laser irradiation. Both in vitro and in vivo antitumor results have demonstrated the predominant effect of supramolecular nanomedicines, compared to DOX or CuS NPs, exhibiting better antitumor growth performances. These results highlight the promise of CuS-DOX@PCM-CD@HA-Fc in combining chemotherapy, chemo-dynamic therapy and photothermal combined therapy to overcome current limitations of cancer therapies.

The widespread use of plastic products in daily life has raised concerns about the health hazards associated with nanoplastics (NPs). When exposed, NPs are likely to infiltrate the bloodstream, interact with plasma proteins, and trigger macrophage recognition and clearance. In this study, we focused on establishing a correlation between the unique protein coronal signatures of high-density (HDPE) and low-density (LDPE) polyethylene (PE) NPs with their ultimate impact on macrophage recognition and cytotoxicity. We observed that low-density and high-density lipoprotein receptors (LDLR and SR-B1), facilitated by apolipoproteins, played an essential role in PE-NP recognition. Consequently, PE-NPs activated the caspase-3/GSDME pathway and ultimately led to pyroptosis. Advanced imaging techniques, including label-free scattered light confocal imaging and cryo-soft X-ray transmission microscopy with 3D-tomographic reconstruction (nano-CT), provided powerful insights into visualizing NPs-cell interactions. These findings underscore the potential risks of NPs to macrophages and introduce analytical methods for studying the behavior of NPs in biological systems.