ACS Publications最新文献

Atherosclerosis is driven by metabolic dysregulation, particularly aberrant cholesterol accumulation and impaired nitric oxide (NO) signaling. However, most therapeutic strategies address these abnormalities separately, while biomaterials capable of translating pathological metabolic dysregulation into localized biochemical regulation remain limited. Herein, we report MMCoac@ChOx/HRP, a macrophage membrane-camouflaged coacervate microreactor formed via liquid–liquid phase separation (LLPS). The microreactor features a macromolecularly crowded core self-assembled from poly(diallyldimethylammonium chloride) and sulfobutylether-β-cyclodextrin, which enables cholesterol recognition and enrichment of cholesterol oxidase (ChOx) and horseradish peroxidase (HRP). These co-encapsulated enzymes achieve high enrichment efficiencies of 87.5 and 92.1%, respectively, to drive cholesterol oxidation and subsequent NO generation. In simulated body fluid, MMCoac@ChOx/HRP depleted cholesterol levels from 5.0 to 2.9 ± 0.4 mM and generated 12.1 ± 0.8 μM NO within 12 h. In vitro, it significantly attenuated macrophage foam cell formation and promoted endothelial repair. Furthermore, following systemic administration in ApoE^–/– mice, MMCoac@ChOx/HRP preferentially accumulated in atherosclerotic aortic plaques, enhanced in situ NO generation, and reduced aortic plaque burden from 27.4 ± 4.5 to 8.2 ± 3.0%. Overall, this study demonstrates a localized metabolic intervention strategy driven by an LLPS-based microreactor. This versatile biomaterial platform effectively modulates the plaque microenvironment, holding great potential for therapeutic interventions against metabolic syndrome.

Insufficient Li⁺ transport kinetics and poor interfacial stability hinder the practical application of polyethylene oxide (PEO)-based solid-state electrolytes (SSEs) in all-solid-state lithium metal batteries. In this work, we propose iodine-induced charge transfer of a covalent organic framework (COF) as an effective strategy to achieve fast ion transport and a stable SSE/Li interface. First, the electron-deficient COF skeleton in the I₂/COF charge-transfer complex anchors TFSI^- anions through enhanced electrostatic interactions, thereby promoting the dissociation of lithium salt to release free Li⁺. Second, the electron deficiency of COF strengthens its dipole–dipole interactions with PEO, leading to suppressed PEO crystallization and enhanced COF/PEO compatibility. Third, the electron-deficient COF tailors the Li⁺ coordination environment via weakening the affinity of PEO and COF toward Li⁺. Consequently, the I₂/COF charge-transfer complex accelerates Li⁺ transport kinetics in PEO-based composite SSEs. Furthermore, the confinement effect of COF toward I₂ via charge transfer effectively inhibits the aggressive lithium anode corrosion by I₂, resulting in the controlled growth of a stable, robust, and conductive solid electrolyte interface (SEI) rich in LiF and LiI. Thus, the I₂/COF charge-transfer complex enables excellent rate capability and cycling stability of the resulting COF/PEO-based composite SSE, maintaining a capacity retention of 88.58% after 1000 cycles at 2 C. This work offers a promising strategy for designing COF/PEO-based composite SSEs for next-generation all-solid-state lithium metal batteries.

Interfacial quality at the SnO₂ electron transport layer (ETL)/perovskite junction critically governs the electron collection and device performance in n-i-p type perovskite solar cells (PSCs). However, the defects within SnO₂ and at the buried interface can impede electron extraction and promote charge recombination. Herein, cesium hexafluorophosphate (CsPF₆) was introduced into the SnO₂ precursor as an interfacial additive. Calculations and experimental measurements indicate that the F atoms of PF₆^– coordinate with undercoordinated Sn sites, whereas Cs participates in the formation of an FA-Cs alloyed layer at the buried perovskite surface. These interactions establish a molecular bridge across the SnO₂/perovskite junction. The resulting bridge suppresses the interfacial defects, improves the energy-level alignment and physical contact, and regulates the perovskite crystallization. The devices incorporating CsPF₆ deliver a champion power conversion efficiency (PCE) of 24.25%. They also show enhanced stability. The unencapsulated devices retain 90.05% of their initial PCE after 1000 h of aging in ambient air. These findings demonstrate that molecular bridging is an effective route to simultaneously improve the efficiency and stability of PSCs.

The chronic recurrence of psoriasis is driven by a self-amplifying inflammatory cascade in which oxidative stress and mitochondrial metabolic dysfunction reinforce each other, and single-target conventional therapies often fail to break this cycle. Here, we present a micro–nano hybrid system, Mito-Ce, constructed by covalently immobilizing ceria nanozymes (CeNPs) onto the surface of isolated functional mitochondria through thiol–maleimide chemistry. This design endows the hybrid with dual functionalities, including mitochondrial bioactivity and durable ROS-scavenging capabilities of CeNPs. In H₂O₂-stimulated macrophages, upon internalization. Mito-Ce markedly reduced intracellular ROS and consequently suppressed the secretion of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). Topical application of Mito-Ce to an imiquimod-induced mouse model of psoriasis visibly resolved psoriatic plaques, reduced the PASI score, and reversed epidermal hyperplasia. Beyond local repair, Mito-Ce rebalanced systemic immunity, evidenced by a decline in splenic pathogenic Th17 cells and polarization toward anti-inflammatory M2 macrophages. Transcriptomic profiling further revealed that Mito-Ce broadly reversed the pathological gene expression program, downregulating stress-responsive and phagocytosis-related genes while upregulating genes associated with metabolism, epidermal proliferation, and tissue homeostatic remodeling. These coordinated networks ultimately re-established immune–barrier homeostasis at the molecular level. Collectively, by integrating nanozyme-mediated ROS scavenging with mitochondrial bioactivity, the Mito-Ce hybrid could treat psoriasis through coordinated disruption of the inflammatory cascade, potentially offering a highly effective platform for various chronic inflammatory disorders.

Developing efficient, low-cost, multifunctional additives that require small amounts and can simultaneously protect both the cathode and anode remains a major challenge for the practical application of lithium batteries. Herein, bis(2,4-dimethylpentane-2,4-glycolato)diboron (B₂hmp₂) was introduced to construct a greatly Li⁺-conductive cathode electrolyte interphases (CEIs) at the LiNi_0.8Co_0.1Mn_0.1O₂ (NCM811) surface together with robust solid electrolyte interphases (SEIs). Using a common electrolyte with 0.2 wt % B₂hmp₂, the Li||Li cells deliver markedly enhanced long-cycling stability, sustaining stable operation for 500 h at 0.5 mA cm^–2. Furthermore, following 350 cycles at 0.5 C, the capacity retention of 4.5 V Li||NCM811 cells was elevated from 57.2 to 83.6%. Experimental results reveal that the thin, uniform, boron-rich CEI generated by B₂hmp₂ effectively mitigates particle microcracking and restrains the dissolution of transition metal ions. Interface analysis reveals that the modified SEI film enriched with B–O species and LiF facilitates uniform Li plating/stripping without dendrite formation and reduces the continuous parasitic decomposition of electrolyte solvents. This article highlights the value of trace diboron for forming desirable electrolyte interphases to obtain the wonderful long-term cycle performance and rate performance of Li||NCM811 cells.

Solid-state sodium metal batteries are promising candidates for grid-scale energy storage due to their inherent safety and low cost. However, the development of solid electrolytes that support high-rate (>20 C) cycling for fast-charging applications remains a major challenge. Herein, we explore how adding SiO₂ affects the ionic conductivity and dendrite suppression of NaB₃H₈, to develop superior solid electrolytes for high-rate batteries. The composites featuring an amorphous passivating layer with B–O bonds were fabricated via ball milling. Among them, NaB₃H₈-40%SiO₂ exhibits the best conductivity, reaching 0.62 mS cm^–1 at 25 °C, 2 orders of magnitude higher than that of pristine NaB₃H₈. Crucially, by reducing electronic conductivity and enhancing mechanical strength, it possesses a high critical current density of up to 6.5 mA cm^–2, significantly higher than that of other reported hydridoborates. The Na/NaB₃H₈-40%SiO₂/TiS₂ batteries exhibit superior rate capability (216.4 mAh g^–1 at 1 C and 143.1 mAh g^–1 at 20 C) and long-term cycling stability (nearly 100.0% capacity retention after 2000 cycles at 20 C) at 30 °C. This work offers a promising approach for the development of innovative solid electrolytes in fast-charging or high-power-density sodium metal batteries.

Head and neck squamous cell carcinoma (HNSCC) remains difficult to treat, and conventional chemotherapy has limited efficacy and substantial toxicity. We developed a VYQFF peptide-modified brucine liposome (Bru-VYQFF-Lip) and characterized its particle size, zeta potential, polydispersity, encapsulation efficiency, and drug loading. Bru-VYQFF-Lip showed greater uptake in Trop2-high HSC3 cells than in HOK cells and inhibited HNSCC-cell proliferation, migration, and invasion while promoting apoptosis. After intratumoral administration, the VYQFF-modified formulation showed greater local fluorescence retention than the NHS-bearing, non-peptide comparator; this experiment does not establish systemic tumor targeting or direct Trop2-specific recognition. Bru-VYQFF-Lip also suppressed tumor growth in a nude-mouse xenograft model. Terminal serum chemistry and organ histology did not reveal overt hepatorenal or histopathological injury, although the safety assessment was limited by the absence of complete longitudinal and hematological evaluation. Bioinformatic and experimental analyses identified INHBA as a candidate mediator associated with poor prognosis. Mechanistic experiments were consistent with suppression of the INHBA/TGF-β/Smad axis and epithelial-mesenchymal transition. These findings support further evaluation of VYQFF-functionalized brucine liposomes, including physicochemically matched controls, receptor-blocking studies, systemic biodistribution experiments, and comprehensive toxicology.

Crystal structure prediction (CSP) plays a significant role in exploring the crystal polymorphism of pharmaceutical solids. Determination of the atomic-level structures of crystalline materials is a fundamental step in understanding their bulk physical and chemical properties and behavior in drug products. CSP can be performed using numerous computational approaches, but all ultimately require comparison with experimental measurements to confirm the CSP findings. In this work, terahertz (THz) vibrational spectroscopy is combined with powder X-ray diffraction (PXRD) to demonstrate a new metrics framework for the validation of CSP investigations. Terahertz spectroscopy probes the low-frequency (≤150 cm⁻¹) lattice vibrations of molecular crystals and provides a polymorph specific spectral profile that complements diffraction methods. This methodology is applied to the anti-epileptic drug lamotrigine, the subject of multiple crystal engineering studies to improve its formulated performance. A CSP search was performed on lamotrigine starting with a fast molecular mechanics survey for initial crystal structure candidates (∼800,000 structures), followed by high-accuracy solid-state density functional theory to refine the most promising candidates. The accuracy of the CSP output was evaluated by numerical comparison of simulated and experimental PXRD and THz datasets, with both benchmarks unambiguously indicating the lowest energy CSP candidate to be a structural match to the published lamotrigine polymorph (Form I, C 2/c space group). The success of the overall approach highlights THz spectroscopy as an effective orthogonal experimental benchmark for CSP and the combined experimental validation process represents a compelling procedure for advancing predictive solid-state modeling of pharmaceutical materials.

Supramolecular assembly of small molecules occasionally leads to viscoelastic materials like supramolecular gels that are important for various applications in material science including drug delivery. However, the a priori design of such soft materials remains an elusive goal. Understanding of the supramolecular synthon and its importance in the context of crystal engineering proved to be handy in occasional prediction of gelation. Herein, we report the supramolecular synthon-driven design, synthesis, and single-crystal structures of a series of diacylhydrazines as potential supramolecular gelators. Conjugation of various arylcarboxylic acids including a few non-steroidal-anti-inflammatory drugs (NSAIDs), namely, naproxen (NAP), ibuprofen (IBU), and flurbiprofen (FLB), with hydrazine afforded seven diacylhydrazine molecules, all of which were found to be gelators of various solvents. The gels were routinely characterized by dynamic rheology and electron microscopy. While hydrogen-bonded self-assembly involving the N−N fused amide moieties in these molecules as revealed by single-crystal structures appeared to have played a pivotal role in gelation, one such gelator NAP_Hydz showed the capability of loading drugs like sulfasalazine or SUL (NSAID) and doxorubicin or DOX (anti-cancer) onto the corresponding supramolecular gel matrix. In vitro studies revealed that the drug-loaded xerogels, i.e., NAP_Hydz@SUL (xerogel) and NAP_Hydz@DOX (xerogel), were effective in reducing inflammation in inflamed normal cells RAW 264.7 and killing melanoma cells (B16−F10), respectively. The rheoreversibility, injectability, and shape sustainability of the supramolecular gels of NAP_Hydz suggested a plausible drug delivery application via the topical route.

Current birefringent crystals (e.g., MgF₂, α-BBO, and YVO₄) are limited by either small birefringence or insufficient deep-UV transparency. Achieving both properties simultaneously remains a key challenge. To address this issue, recent research based on the “confined π-conjugated” strategy has turned its attention to fluoroaluminoborates. In this structural design, non-π-conjugated [Al−O/F] units connect and isolate planar π-conjugated groups, effectively broadening the bandgap while maintaining optical anisotropy. Building on this concept and incorporating different cations, this study reports two new fluoroaluminoborate compounds: CaAlB₃O₆F₂ (CABOF) and its isostructural analogue, PbAlB₃O₆F₂ (PABOF). In PABOF, the introduction of Pb²⁺ induces local structural distortion, thereby enhancing the optical anisotropy. Both CABOF and PABOF exhibit birefringence values exceeding 0.1 at 546 nm, with PABOF demonstrating the largest birefringence among the known fluoroaluminoborates. In addition, both compounds exhibit excellent thermal stability. This work identifies two potential UV-birefringent materials, further enriching the fluoroaluminoborate family.