Latest ArticlesUlcerative colitis (UC) is a chronic inflammatory bowel disease featured by dysregulated immune responses and compromised intestinal barrier function. Current therapies often suffer from limited efficacy and systemic side effects due to non-specific drug distribution. Here, we developed macrophage membrane-camouflaged nanovesicles (mcNVs) for targeted delivery of emodin (Emo) to inflamed colon tissues. The biomimetic nanovesicles were fabricated by fusing J774A.1 macrophage membranes with Emo-loaded liposomes, inheriting the parent cells' chemotactic homing capabilities while maintaining excellent drug loading and colloidal stability. Systematic characterization confirmed successful membrane integration, as evidenced by transmission electron microscope (TEM) imaging, particle size, and ζ potential analyses. In vitro studies demonstrated favorable sustained release and enhanced cellular uptake of Emo-loaded mcNVs (Emo-mcNVs) compared to conventional liposomes. In a sodium dextran sulfate (DSS)-induced murine colitis model, Emo-mcNVs exhibited superior colon-targeting capability through chemokine gradient recognition (C-C motif chemokine ligand (CCL)2/3/5), resulting in significantly improved therapeutic outcomes versus free Emo and 5-aminosalicylic acid controls. Treatment with Emo-mcNVs attenuated disease severity (reduced disease activity index (DAI) score), preserved the colon architecture, and decreased pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6). Biodistribution studies using multimodal imaging confirmed specific accumulation in the inflamed colon tissue with minimal systemic exposure. This study presents a novel biohybrid delivery system that leverages the pathophysiology of UC for targeted therapy, offering a promising translational approach for inflammatory bowel diseases.
Phosgene, a highly toxic chemical warfare agent and industrial hazard, poses significant environmental and health risks, necessitating the development of rapid and reliable detection methods. Herein, we present a novel near infrared Ⅱ (NIR-Ⅱ) fluorescent probe based on silicon rhodamine and an o-phenylenediamine-responsive group for the sensitive and selective detection of phosgene. In the presence of phosgene, it generates a distinct color change and lights up NIR-Ⅱ (900 nm) emission, enabling both naked-eye visualization and fluorescence in vivo analysis. The probe shows rapid exceptional selectivity for phosgene and achieves rapid detection in solutions, gases, and soils. Notably, we successfully utilize this probe for in vivo imaging in Arabidopsis thaliana, enabling high signal-to-noise ratio real-time monitoring of phosgene within plant systems with minimal interference from autofluorescence. This work advances the design of reaction-based NIR-Ⅱ probes for hazardous chemical monitoring, combining simple operation, high sensitivity, and broad applicability, thereby contributing to environmental safety and sustainability.
Nitric oxide (NO), a significant signaling molecule, plays essential roles in diverse physiological and pathological processes including cell senescence. Lysosomes are recognized as pivotal subcellular organelles of cellular senescence, whereas the influence of senescence on lysosomal NO homeostasis remains poorly understood. To explore the potential association between cellular senescence and alterations in lysosomal NO levels, herein, we developed FL-O1, a novel ratiometric fluorescent probe specifically designed for lysosomal NO detection. The probe selectively reacts with NO through the recognition unit of o-phenylenediamine, forming an extended conjugated system that generates a distinct ratiometric optical signal with exceptional sensitivity (detection limit = 95 nmol/L). FL-O1 exhibits versatile applications in both in vitro and in vivo contexts. It successfully visualizes exogenous and endogenous NO dynamics in live zebrafish models and enables specific monitoring of lysosomal NO levels in cellular systems. Importantly, the probe was utilized to quantitatively evaluate NO levels in senescent states of cancer and healthy cells. The results revealed two key insights: (1) Senescent cells consistently maintain higher NO concentrations compared to their non-senescent counterparts, and (2) senescent healthy cells exhibit elevated NO levels relative to senescent cancer cells. This innovative small-molecule probe represents a significant advancement in lysosomal NO imaging technology. Its unique design and capabilities provide a powerful tool for investigating the role of lysosomal NO in cellular senescence, potentially uncovering novel mechanistic insights and facilitating the development of targeted therapeutic strategies for senescence-related disorders.
Extracellular vesicles (EVs), mainly comprising microvesicles (MiV) and exosomes (Exo), were successfully isolated from normal human embryonic kidney cells (HEK293T) and demonstrated specific uptake by human tongue squamous cell carcinoma cells (SCC-9). Initial mechanistic investigations revealed that both MiV and Exo were mainly internalized via endocytic pathways and predominantly relied on the surface proteins of SCC-9 cells for specific uptake. Furthermore, Exo, with better stability and uptake efficiency, were chosen as the carriers of the clinical drug cisplatin (CDDP) for the treatment of tongue cancer. Comprehensive in vitro and in vivo evaluations demonstrated that the Exo-CDDP system exhibited remarkable biocompatibility, mitigated drug-related toxicity and minimized CDDP efflux from tumor cells, and displayed potent anti-tumor efficacy. These findings collectively indicated that HEK293T-derived Exo represent a highly promising drug delivery platform for tongue cancer therapy, while simultaneously offering innovative ideas for the development of versatile Exo-based therapeutic delivery systems.
Core-shell capsules are excellent carriers, showing good performances in cargo protection and controlled release. However, the controlled encapsulation of solid particles in capsules remains a great challenge, severely limiting their widespread applications. Here, a millifluidic system assisted by periodic vibrations is developed to precisely control the preparation of particle-loaded capsules. A high-frequency low-amplitude vibration is applied to prevent the jamming of solid particles by shaking and a low-frequency high-amplitude vibration is applied to synchronize the feeding of solid particles and the emulsification of capsules by generating a periodic flow pulse. The phase diagrams of particle-loaded capsules are systematically investigated with respect to various experimental parameters to provide guidances for the controlled preparation process. The developed millifluidic system offers a versatile platform to precisely prepare core-shell capsules loaded with different sizes, types and numbers of particles. The prepared particle-loaded capsules possess good biocompatibility, monodispersity, mechanical strength, storage stability and controlled release, paving the way for their widespread applications.
Cysteine (Cys), as a key precursor of glutathione (GSH) and an essential component of the thiol antioxidant system, plays a dual role in the pathological progression of Alzheimer’s disease (AD): it participates in antioxidant defense mechanisms while also potentially exacerbating neurological damage through metabolic dysregulation. Investigating the dynamic regulatory mechanisms of Cys in AD progression serves as a critical bridge linking oxidative stress, metabolic dysregulation, and neurodegenerative degeneration. High-resolution in vivo imaging of Cys dynamics in AD brains remains an unmet need. In view of the instability of the fluorescent probe of acrylyl group and the lack of specificity for Cys. This work introduced chlorine atoms into the probe structure, and achieved dual modifications: (1) Converting the nucleophilic addition mechanism into an SN2 substitution; (2) modulating the conjugation effects between the formyl group and the three-position double bond. In this way, the stability of the probe, the high specificity of Cys, and the crossing of the blood-brain barrier are addressed. Through in situ imaging in AD models, we have demonstrated a pathological reduction in Cys levels during AD. Furthermore, as Cys serves as the core molecule in the regulation of ferroptosis, it was found that ferroptosis can mediate the down-regulation of Cys in AD through ferroptosis inducers and inhibitors. This study is not only to reveal the core pathological mechanism of AD, but to provide theoretical basis and technical support for early diagnosis, targeted therapy and personalized medicine.
Polymer dielectric capacitors are crucial for advanced power electronics but are often limited by the trade-off among energy density, efficiency, and thermal stability under high electric fields. To overcome these challenges, we propose a multiscale chemical configuration design strategy by constructing a ternary composite comprising high glass transition temperature fluorene polyester (FPE), polyetherimide (PEI), and high-aspect-ratio γ-Al2O3 nanosheets (AO NS). At the molecular scale, the structural compatibility between FPE and PEI enables homogeneous blending, while the incorporation of PEI increases free volume, enhances dipolar mobility, and preserves low dielectric loss. At the nanoscale, AO NS act as ceramic barriers to suppress charge injection, raise interfacial polarization, and stabilize the local electric field. At the device level, this hierarchical design leads to synergistic improvements in dielectric properties, insulation, and energy storage performance. As a result, the optimized composite achieves excellent high-temperature energy-storage capability, characterized by a high energy density of 5.51 J/cm3 with above 80% efficiency at 150 ℃ and 550 MV/m. This study paves a practical and scalable path toward high-performance polymer dielectrics for reliable energy storage under extreme thermal and electrical conditions.
Biomolecular self-assembly systems form the cornerstone of biological structures, in which the interactions between carbohydrates and proteins play a crucial role in many life processes. This has driven the development of biomimetic carbohydrate-protein supramolecular assemblies (BCPSAs), which show great potential in biomedical research. We successfully constructed a novel supramolecular hybrid nanocarrier with pH responsiveness and targeting capabilities based on specific interactions between carbohydrates and proteins. This system self-assembles into nanoparticles CA@MP5 in water through the specific binding of mannose clusters on glycosylated pillar[5]arene MP5 with lectin Con A. Additionally, through a host-guest assembly strategy with the synthesized β-d-galactopyranosyl pyridine derivative G, it complexes within the MP5 cavity to form a "double-sweet" supramolecular glyco-nanoprotein (CA@MP5⊃G). This system shows high affinity for the asialoglycoprotein receptor (ASGPR) on HepG2 liver cancer cells. In vitro, the doxorubicin (DOX)-loaded micelles (DCA@MP5⊃G) release drug effectively in acidic environments and significantly inhibit HepG2 cell growth, with reduced toxicity toward normal cells. In vivo, the nanocarrier targets tumors effectively, reducing systemic toxicity and inhibiting tumor growth. This study offers a novel construction strategy for drug delivery systems based on carbohydrate-protein interactions in anti-tumor applications, which is significant for enhancing therapeutic efficacy.
Achieving efficient and sustainable hydrogen production from methanol electrolysis requires significant advances in catalyst design. In this study, we present a novel strategy where nickel selenide, featuring distinct crystal phases, anchors on mesoporous hollow carbon spheres to synergistically enhance the activity of Pt for methanol-assisted water splitting reactions. The heterostructured NiSe/NiSe2 nanosheets modulate the electronic structure of Pt, positioning it closer to an optimal thermodynamic state, and creating a highly oxophilic environment that accelerates charge transfer and optimizes the adsorption and desorption of reaction intermediates. The engineered hybrid catalyst exhibits exceptional enhancements in both mass and specific activity for methanol oxidation, significantly outperforming commercial catalysts. In addition, the catalyst exhibits a high electroactive surface area, an abundance of active sites, fast catalytic kinetics, and excellent stability. Notably, a methanol electrolyzer utilizing this catalyst achieves a current density of 10 mA/cm2 at only 0.67 V, a remarkable 1.08 V reduction compared to the voltage required for conventional water electrolysis (1.75 V). This work provides a transformative strategy for designing high-performance electrocatalysts, offering new pathways for more efficient and sustainable hydrogen production through methanol electrolysis.
Alkylated arenes, which are prevalent molecular building blocks, are widely applicable across various scientific domains. However, regioselectively alkylating arenes often poses significant challenges, despite their apparent simplicities. Herein, we report the first examples of substrate-controlled photocatalyzed regiodivergent alkylations of aromatic nitriles. The judicious choice of alkyl halide facilitated selection of mechanistically divergent processes. The two reaction manifolds, an ipso-substitution path that proceeds via radical coupling and a Friedel−Crafts-type C–H alkylation via quantum mechanical tunneling, enabled selective access to regioisomeric alkylated arenes. Mechanistic investigations combined with density functional theory (DFT) calculations shed light on the origin of this regioselectivity switch. Remarkably, this process exhibited superior efficiencies, reactivities, and synthetic utilities, and can be performed on the gram scale.
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