Single-dose mSEB-mi3 nanoparticle vaccine elicits robust humoral immunity and protects mice against SEB intoxication and MRSA infection.

Rolling circle amplification-based self-assembled CpG nanoparticles: Immune activation and prevention of Edwardsiella piscicida.

In this work, the self-assembly behaviors of tetracarboxylic acid derivatives (EBTD, BCPTD, and DETD) and their co-assembly behaviors with pyridine derivative PEBP-C8 were investigated by scanning tunneling microscopy (STM) and density functional theory (DFT). EBTD, BCPTD, and EBTD molecules self-assembled into similar regular grid structures by forming O-H···O hydrogen bonds. Especially, with a meta-dicarboxylic group, DETD molecules could aggregate into another kind of dimeric building block, leading to more diversified self-assembly nanostructures. With the introduction of PEBP-C8, all of the O-H···O hydrogen bonds in EBTD and BCPTD systems were broken and O-H···N hydrogen bonds were formed with PEBP-C8. In contrast, for the DETD/PEBP-C8 system, partial O-H···O hydrogen bonds were retained along with the new O-H···N bonds with PEBP-C8. Both EBTD and BCPTD co-assembled with PEBP-C8 to form acid-pyridine-acid-pyridine nanostructures. Nevertheless, DETD not only assembled with PEBP-C8 into an acid-pyridine-acid-pyridine nanostructure but also formed a pyridine-acid-acid-pyridine nanostructure.

Self-Assembling RNA Nanostructures are Highly Sensitive to Environmental Conditions.

In musculoskeletal tissue engineering, there is a need for bone implants that are biocompatible, resorbable, promote tissue regeneration, and degrade at a rate matching healing. Polycaprolactone (PCL), an FDA-approved biodegradable and bioinert polymer, can be functionalized with natural components without harsh crosslinking. This study presents the first demonstration of a homogeneous bulk polycaprolactone-gelatin (PCL-gelatin, PG) composite containing self-assembled gelatin nanoparticles that retain bioactivity despite thermal processing for 3D printing applications. PG composites with varying gelatin content (10%, 20%, and 30%) and β-tricalcium phosphate incorporation were fabricated through casting and melt processing into printable filaments at 110°C. Comprehensive characterization using mechanical testing, contact angle measurements, FTIR, TGA, EDS, and SEM confirmed homogeneous gelatin distribution as nanoscale particles throughout the PCL matrix, with systematic increases in hydrophilicity and enhanced mechanical properties proportional to gelatin content. Accelerated degradation studies revealed tunable degradation rates correlated with gelatin concentration, while invitro studies with human mesenchymal stem cells demonstrated enhanced proliferation and early osteogenic differentiation markers, particularly in PG30 compositions. Subcutaneous implantation in rats over 24 weeks showed biocompatibility comparable to PCL with minimal inflammatory response and biphasic degradation behavior characterized by initial swelling followed by controlled volume reduction. In critical-size femoral defects, PG30 exhibited superior early mechanical properties and increased preosteoblast density at bone interfaces compared to PCL and PCL-TCP controls at 4 weeks. This developed fabrication methodology enables precise spatial control through 3D printing while preserving gelatin bioactivity. This approach offers a promising advancement for tissue engineering applications requiring enhanced cellular interactions and controlled degradation.

Engineered phytic acid-lignin networks: one-pot strategy toward stable, multifunctional bio-based materials.

Two-component nanoparticle self-assembly: Modeling, analysis, and structure control

The self-assembly of polymer-grafted nanoparticles (PGN) has drawn interest as a platform approach for the fabrication of hybrid materials in which novel functionalities, such as photonic or phononic band gap formation, arise from the interplay of microstructure regularity and brush interactions. However, the complex dynamical processes associated with polymer and particle constituents render PGN assembly structures susceptible for the arrest of metastable states and impart sensitivity of physical properties to process conditions. For the case of poly(methyl methacrylate) (PMMA)-grafted silica particles, the use of volatile solvents (such as tetrahydrofuran) during film formation results in metastable microstructures with reduced effective medium sound velocity but increased width of the band gap as compared to equilibrated films cast from toluene solution. The linear acoustic dispersion obtained from Brillouin light spectroscopy combined with elastodynamic calculations suggest that the use of volatile solvents increases the free volume of PMMA, while maintaining the local order of particles within the film. Surprisingly, stop-band formation was more pronounced in metastable microstructures. The origin for this unusual behavior resides in the hybridization mechanism underlying the gap formation. Thus, the increased contrast of elastic constants 'overcompensates' the loss of long-range positional order and amplifies the hybridization gap that originates from the dipolar (ℓ = 1) resonance of the SiO2 cores coupled to the polymer grafts of neighboring PGNs.

Manipulation of kinetic pathways is essential to self-assemble nanoparticle building blocks into complex ordered structures, as the emergence of intermediate metastable states could either facilitate or hinder crystallization of the target lattice. Molecular simulations and Markovian and transition state theory are used to validate our conjecture that intermediary mesophases, with partial but long-range translational or orientational structural ordering, accelerate crystallization kinetics from the disordered structure. Using four representative models, two lyotropic single-component and two thermotropic binary mixture systems, we demonstrate that mesophases with intermediate entropies, such as nematic fluid, rotator solid, and microsegregated mesophases, speed up the overall crystallization rate. This enhancement occurs by effectively splitting a larger isotropic-to-crystal free energy barrier into two smaller barriers corresponding to isotropic-to-mesophase and mesophase-to-crystal transitions, with mesophase "bulk" macrostates being kinetically more favorable than microscopic fluctuations. The single-step isotropic-to-crystal transition occurs through a composite-cluster pathway that includes mesophase microdomains; an isotropic-crystal interfacial energy greater than or comparable to the sum of the isotropic-mesophase and mesophase-crystal interfacial energies is associated with enhanced two-step crystallization rate. Overall, our findings validate the conjecture, which offers additional guidance for selecting nanoparticle designs and conditions that promote efficient crystallization pathways.

Macromolecular coupling is a widely used technique for industrial materials, while supramolecular coupling is ubiquitous in biological systems. Although the designed synthesis of one-dimensional self-assembled nanostructures via crystallization-driven self-assembly and liquid-crystallization-driven self-assembly has been realized, end-to-end coupling of cylindrical micelles is rarely reported. Unlike crystallization, liquid-crystallization features fluidity under certain conditions. The cylindrical micelles prepared via liquid-crystallization-driven self-assembly possess less organized liquid crystalline blocks at the two partially open ends, originating the end-to-end coupling to lower the free energy. The interaction strength of solvents with liquid crystalline blocks is a pivotal parameter that can be used to switch on or off the coupling. Theoretical simulation is consistent with experimental work, supporting the mechanism. The supramolecular coupling offers opportunities for designing complex polymeric liquid crystalline nanostructures.

Rapid and robust molecular fingerprinting is critical in biomanufacturing, diagnostics, and environmental monitoring. Nanopore sensing provides single-molecule readouts as transient ionic current pulses; however, conventional analyses depend on handcrafted features that miss informative structural information. We present an interpretable machine learning framework that operates directly on raw pulses, pairing a physics-guided time-frequency transform with a compact neural classifier and feature-attribution maps. We also include conventional feature-based SVMs and a 1D classifier trained on raw pulses as baselines. On two self-assembled DNA nanostructures of similar size but distinct geometry, for which standard pulse features overlap, the method achieves high accuracy and yields physically consistent attributions that highlight discriminative signal motifs. A matched control without the time-frequency transform clarifies when learned filters suffice versus when physics-guided preprocessing improves reliability, leading to a practical "custom-filter" design principle. The workflow is modular, lightweight, and applicable to pulse-based sensing platforms, including virus and exosome analysis, electrochemical monitoring, and industrial fault detection. By combining accuracy with transparency, it lays the groundwork for deployable sensing platforms in regulated, mission-critical settings.

Albumin-hitchhiking self-assembly full-API nanoparticles for imaging-guided photodynamic potentiating tumor immunotherapy.

Oxidative stress disrupts the synthesis-degradation balance of the extracellular matrix in osteoarthritic (OA) cartilage, resulting in the loss of type II collagen (COLII). Here, we developed self-assembled nanoparticles (PE@NPs) driven by hydrophobic interaction, π-π stacking interactions and hydrogen bonding, forming an epigallocatechin-3-gallate (EGCG) core and a polyethylene glycol (PEG) shell. Compared with free EGCG, which possesses potent but short-lived antioxidant activity, PE@NPs improved molecular stability, extending reactive oxygen species scavenging activity to 24 h. Furthermore, PE@NPs significantly suppressed interleukin-1 β-induced COLII degradation in OA chondrocytes. Transcriptomic analysis revealed that PE@NPs upregulated genes involved in antioxidant defense (Selenop), cartilage homeostasis (Cytl1 and DKK3) and subchondral bone remodeling (Omd). In vivo, PE@NPs exhibited a more significant therapeutic effect than free EGCG, notably attenuating COLII degradation and improving subchondral bone mass, thereby delaying OA progression. Overall, these findings identify PE@NPs as a safe and effective therapeutic approach for OA.

The nanobased drug delivery system has become a responsive and potential therapeutic approach for the therapeutic implication against multidrug-resistant bacterial infections and malignant cells with a convenient synthesis process, customization, and site-specific active targeting. In this study, self-assembled peptide-functionalized silver nanoparticles (SAP@AgNPs) were fabricated via a bottom-up approach using NaBH4 as a reducing agent. The physicochemical properties of the synthesized SAP@AgNPs were observed by various standard characterization techniques, like UV-vis, FTIR, XPS, TEM, FE-SEM, DLS, ZETA, and XRD, which reveal a self-assembled nanostructure having a dipeptide on its surface. SAP@AgNPs showed dose-dependent antibacterial efficacy against clinically isolated multidrug-resistant Staphylococcus aureus and Escherichia coli bacterial strains. Notably, SAP@AgNPs demonstrated superior antibacterial activity against E. coli (MBC: 0.04 nM) compared to S. aureus (MBC: 0.05 nM). The synthesized SAP@AgNPs were further evaluated for their anticancer potency against leukemic cells (K-562), where the IC50 was found to be 0.029 nM concentration of the functionalized nanoparticles. Elevated levels of oxidative stress formation because of considerable ROS generation following treatment with SAP@AgNPs may lead to effective antibacterial and anticancer activity. The SAP@AgNPs demonstrated negligible hemolysis (≤2%) at concentrations up to 0.04 nM. In contrast, the IC50 values for SAP@AgNPs against HEK-293 and PBMCs were determined to be 0.035 and 0.155 nM, respectively, suggesting the particles' biocompatibility. Furthermore, it was established by various in silico approaches that SAP@AgNPs potently interacted with distinct cell surface proteins of the tested bacterial strains as well as cancer cells. Furthermore, multiple in silico techniques revealed that SAP@AgNPs strongly interacted with distinct cell surface proteins of the investigated bacterial strains as well as cancer cells, which could be the key component in the entire study's high biological effectiveness.

New SARS-CoV-2 variants pose an ongoing threat due to persistent immune escape of natural and vaccine-induced immunity. The emergence of BA.1 (Omicron) produced a large antigenic shift in the spike protein, rendering many antibodies ineffective with concomitant loss of Emergency Use Authorization (EUA) status. While strains have evolved far from BA.1, re-emergence of variants from branches closer to BA.1 are of recent concern. Here, we engineered a self-assembling nanoparticle displaying RBD 4mut g5.1, an immunogen developed using structure-guided design to focus antibody responses to the receptor binding site (RBS) epitope and promote cross-reactivity by inclusion of four rationally selected BA.1 mutations in the RBS. Unlike multi-component RBD approaches, we demonstrate a single, rationally designed component is sufficient for generating broad immunity. We demonstrate that in both naïve and antigen-experienced mice, RBD 4mut g5.1 nanoparticle induced cross-reactive and durable antibody responses capable of potent neutralization of ancestral SARS-CoV-2 and many Omicron variants. RBD 4mut g5.1 provided heterologous protection at a memory timepoint. By showcasing how subtle changes in an epitope can trigger a diversified antibody response, this study offers a promising new avenue for developing vaccines that can more effectively tackle the ever-evolving threat of immune escape, not only against SARS-CoV-2 but potentially against a range of variable pathogens.

Plant-derived self-assembled nanoparticles, especially from food-medicine homology sources, are gaining attention, yet their structure-function relationships remain unclear. This study identified such nanoparticles from leaf decoction of Eucommia ulmoides, a key plant in traditional Asian medicine and diet, termed EUPs. These spherical particles (~287.8 nm) were primarily composed of polysaccharides and polyphenols, with 268 polyphenolic compounds detected via UPLC-QTOF-MS. Stepwise dissociation-ultrafiltration and spectroscopic analyses revealed that polyphenols were bound to the polysaccharide through noncovalent interactions, including hydrogen bonding and hydrophobic forces, forming a layered structure with sustained-release and thermo-responsive properties. Compared with free polyphenols, EUPs exhibited significantly prolonged anti-inflammatory effects in LPS-stimulated RAW 264.7 macrophages, reflected by the suppression of key inflammatory cytokines, including TNF-α, IL-6 and NO. Therefore, it aims to offer mechanistic insights into the multi-component synergistic anti-inflammatory effects of E. ulmoides and supporting the material basis of food-medicine homology.

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. Development of an E1E2-based HCV vaccine has been hindered by the difficulty of producing a soluble E1E2 (sE1E2) antigen that faithfully recapitulates the native virion-associated heterodimer. Guided by cryo-electron microscopy (cryo-EM) structures, we engineer genotype 1a H77 sE1E2 by truncating the E1 and E2 stems (Cut1), deleting a putative fusion peptide-containing region in E1 (Cut2), and stabilizing the heterodimer using diverse scaffolds. All H77 sE1E2.Cut1+2 scaffolds exhibit native-like E1-E2 association and strong binding to the broadly neutralizing antibody (bNAb) AR4A. A genotype 1a HCV-1 sE1E2.Cut1+2 variant scaffolded by a modified SpyTag/SpyCatcher (SPYΔN) is selected for in vitro and in vivo characterization, as well as further construct refinement. The structure of this HCV-1 sE1E2 construct in complex with bNAbs is determined by cryo-EM and negative-stain EM (nsEM), with an nsEM-based strategy established for antibody epitope mapping. HCV-1 sE1E2.Cut1+2.SPYΔN is displayed on self-assembling protein nanoparticles (SApNPs) to enhance immunogenicity. The HCV-1 sE1E2.Cut1+2.SPYΔN heterodimer and SApNPs bearing wildtype or modified glycans are evaluated in mice, alongside E2 core-based immunogens for comparison. Together,these results establish a framework for advancing E1E2-based HCV vaccines toward clinical development.

Double-network (DN) hydrogels have emerged as promising candidates for flexible supercapacitor applications due to their exceptional mechanical toughness and flexibility. However, their practical use has been limited by poor electrolyte retention and low ionic conductivity, which hinder capacitive performance. In this study, we present a novel DN hydrogel modified through the self-assembly of metal nanoparticles to address these limitations. The hydrogel was synthesized via a combination of physical and chemical cross-linking, followed by in situ reduction of incorporated metal ions to form nanoparticles within the network. The resulting nanocomposite hydrogel exhibited enhanced electrolyte swelling capacity and improved ionic conductivity and maintained robust mechanical flexibility. A flexible supercapacitor (FSC) was fabricated using this modified DN hydrogel as both the electrode and solid-state electrolyte, with activated carbon nanosheets (ACNSs) derived from banana leaves serving as the active material. The ACNSs adhered effectively to the hydrogel matrix with the aid of a polyvinylidene fluoride (PVDF) binder. Electrochemical performance was evaluated in a symmetric two-electrode configuration using 0.5 M sodium sulfate aqueous solution as the supporting electrolyte. The device achieved a high areal specific capacitance (Csp) of 1361 mF cm-2, an energy density (E) of 23 mWh cm-2, and a power density (P) of 700 mW cm-2. Furthermore, the FSC demonstrated excellent cyclic stability, retaining 94% of its initial Coulombic efficiency after 500 cycles. These findings highlight the potential of metal nanoparticle-enriched DN hydrogels as multifunctional materials for next-generation integrated supercapacitors.

Abstract Neutral-density (ND) filters that attenuate light without spectral distortion are essential for imaging and sensing systems. We examine self-assembled sub-100 nm SiO₂ nanoparticle structures in ultrapure water (UPW) as a model platform for color-preserving ND filters. Nanoparticles are synthesized by a Stöber-type process, varying ammonia content, UPW fraction, and stirring rate to control size and monodispersity. Three representative films are selected: Sample A is an ideal monodisperse assembly, Sample B contains small-particle impurities that fill voids, and Sample C contains large-particle impurities that cause crowding. Angle-resolved reflectance shows Bragg peaks whose intensity and sharpness reflect in-plane order. Time-resolved transmittance during drying in UPW indicates that Sample A maintains higher transparency, while Samples B and C deteriorate faster. SEM images, size histograms, and radial distribution functions (RDFs) connect these optical trends to impurity-driven changes in interparticle spacing, guiding future polymer-embedded, tunable ND filters for broadband, color-neutral attenuation in thin-film devices.

Low back pain (LBP) is a widespread global health concern that profoundly impairs patients' quality of life and productivity. Intervertebral disc degeneration (IVDD) is considered a major pathological factor in low back pain, yet the underlying mechanisms of IVDD remain incompletely understood. Current treatment strategies primarily focus on symptomatic relief through medication or surgical removal of degenerated tissue, lacking effective interventions that can reverse the degenerative process. This study investigates the role of fatty acid metabolism in IVDD and proposes a novel therapeutic strategy. Through single-cell sequencing and multi-omics analysis of clinical samples, we identified ACOT13 as a key regulator of fatty acid metabolism. We demonstrated that under pathological conditions, ACOT13 inhibits the AMPK/ACC signaling pathway, leading to disrupted fatty acid metabolism, mitochondrial dysfunction, and subsequently, pyroptosis, which accelerates IVDD progression. Furthermore, we developed an innovative self-assembled nanoparticles based on a traditional Chinese medicine formula. Employing molecular dynamics simulations, we elucidate the self-assembly mechanism, identifying the core constituents and establishing the key roles of hydrophobic interactions, π-π stacking, and hydrogen bonding as the driving forces. Moreover, we revealed that this nano-formulation suppresses ACOT13 function, activates the AMPK/ACC pathway, and improves fatty acid metabolism and mitochondrial function, thereby suppressing pyroptosis and ultimately alleviating IVDD progression. In summary, this study explores a novel mechanism of IVDD from the perspective of fatty acid metabolism and identifies key active components (N-QJZG) from a traditional Chinese medicine decoction, providing new insights for IVDD treatment and promoting the modernization of traditional Chinese medicine research.