ACS Nano
·
2025
·
IF 16
Ying Wang,Jinfu Li,Ding Zhang,Yinyao Feng,Mengni Zhou,Chang Zhou,Dijia Wang,Gaolin Qiu,Wei Dai,Zhilai Yang,Yunjiao Zhang,Li Zhang,Xuesheng Liu,Jiqian Zhang
Current therapies for Alzheimer’s disease (AD) primarily target amyloid-β (Aβ) pathology using monoclonal antibodies, yet their limited efficacy partly results from unintended exacerbation of neural hyperexcitability. This highlights a critical but under-appreciated link between Aβ clearance and neuronal network dysfunction. Here, we designed R@AClipo, a nanotherapeutic platform that codelivers the TREM2 agonist peptide COG1410 and the glutamate modulator riluzole via Angiopep-2–modified liposomes capable of crossing the blood–brain barrier. In AD model mice, R@AClipo upregulated TREM2 expression and enhanced microglial-mediated Aβ clearance. Concurrently, it reduced glutamate accumulation and mitigated neuronal hyperexcitability, as measured by in vivo fiber photometry. Notably, TREM2-driven Aβ clearance alone modestly reduced hyperexcitability, independent of riluzole, contrasting with the excitatory effects frequently associated with antibody-based Aβ therapies. This combinatorial strategy improved cognitive performance and restored neural activity patterns without observable toxicity. Together, these findings support a physiologically compatible strategy that targets the pathological crosstalk between Aβ accumulation and neural hyperexcitability, offering a promising avenue for AD intervention.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Dan Zu,Jun Yao,Xiao Li,Yixing Huang,Can Hu,Mingcong Deng,Qimei Bao,Yin Shi,Zu Ye,Xiangdong Cheng
Gastric cancer (GC) is one of the most common malignant tumors in the world, which is resistant to conventional chemotherapy drugs. Although polyphyllin B (PB) exhibits antitumor activity against GC, its clinical application is limited by systemic toxicity and poor target specificity. Here, we developed a dual-targeting nanoparticle (Ma/HA@NP) coated with a gastric cancer cell membrane (Ma) and hyaluronic acid (HA) to enhance biocompatibility, immune evasion, and homologous targeting. Ma/HA@NPs preserve the immune evasion and homologous targeting properties of both components. Upon endocytosis, Ma/HA@NPs react with cysteine to release PB, deplete glutathione (GSH), and reduce the enzymatic activity of glutathione peroxidase 4 (GPX4), leading to ferroptosis activation. Compared to single PB, Ma/HA@NPs not only enhance PB release but also trigger immunogenic cell death, promoting dendritic cell maturation and cytotoxic T lymphocyte activation. Moreover, interferon-γ release further suppresses cysteine uptake, synergistically amplifying ferroptosis. In vivo, intravenous administration of Ma/HA@NPs-PB in an orthotopic GC model achieved an 85.4% tumor inhibition rate with reduced systemic toxicity compared to free PB. Together, this dual-targeting platform enhances PB delivery and synergizes ferroptosis with immunogenic cell death (ICD) activation, offering a promising strategy for the treatment of gastric cancer.
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MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Zheng Sun,Zhiyong Li,Teng Hao,Xuecun Liu,Yuanyuan Jiang,Songyuge Ping,Na Dong,Ruiling Guo,Xin Yang,Hui Xu
Hepatocellular carcinoma (HCC) is one of the leading causes of death worldwide, accounting for about 90% of all primary liver malignancies. The emergence of natural antitumor compounds provides a new strategy for the treatment of HCC, but their delivery in vivo has become a major problem. In this study, the copolymer of the natural product glycyrrhetinic acid (AMGA) was prepared and served as a carrier for encapsulation of the natural active ingredient Icariside II (AMGA@ICAII). The results show that AMGA still retains the interaction with GA-R and achieves active targeting by interacting with GA-R. In addition, GA-modification changes the physical chemistry nature of the carrier, providing it with better colloidal stability. AMGA@ICAII significantly inhibited the proliferation of the human hepatoma cell line HepG-2 in vitro compared with other treatment groups. Furthermore, AMGA@ICAII improved the distribution of ICAII in the C57BL/6J mouse Hepa1–6 hepatoma model and showed a significant antitumor effect. This work demonstrated that small molecule target modification in the hydrophobic segment of block copolymer will do benefit to improve the performance of the carrier, while retaining ligand–receptor-mediated targeting properties and providing a reference for the targeted delivery of anticancer agents.
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ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Xiaoyu Qin,Wenhao Guo,Yining Wang,Xiangdong Cai,Jianxi Xiao
Pathological collagen emerges as a critical biomarker in the progression of tumors, fibrotic disorders, and osteoarthritis. The precise quantification of pathological collagen holds critical diagnostic value, offering a noninvasive approach for early detection of collagen-associated disorders. A pathological collagen targeting nanozyme biochip (PCC) has been constructed for the first time to ultrasensitively quantify pathological collagen in body fluids. The PCC biosensor consists of a high-affinity pathological collagen targeting nanozyme (Pacotzyme) and a capture surface for efficient enrichment of unbound Pacotzyme. The PCC has been demonstrated to quantitatively analyze pathological collagen across a wide concentration range from 0.1 to 10000 ng/mL, with an LOD as low as 15 pg/mL. PCC demonstrates robust and precise performance in intricate biological environments characterized by elevated protein content, high ionic strength, and increased glucose levels. Moreover, PCC exhibits consistent and reliable functionality in diverse body fluids, including serum, urine, saliva, and synovial fluid. Notably, PCC chips have been successfully applied to detect cancer, fibrosis, and osteoarthritis by quantifying pathological collagen in body fluids. The specific nanozyme biosensor offers a promising diagnostic tool for the early screening and noninvasive diagnosis of collagen-related diseases.
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CANCER RESEARCH
·
2025
·Vol. 85
·期 20
·3999-4017
·
IF 16.6
Zhao Jian,Zhang Weijie,Zeng Yuanyuan,Lu Di,Ma Chenkang,Zhang Mengzhu,Cai Xin,Huang Zhifan,Yang Hongli,Li Jianjun,Zhu Jianjie,Huang Jian-An,Liu Zeyi
Despite progress in tumor-targeted therapy, oncogenic KRAS remains a major challenge in treating lung adenocarcinoma. In clinical practice, KRAS G12C inhibitors have limited response rates and are associated with acquired drug resistance. Cuproptosis is a recently identified form of copper (Cu)-mediated cell death, and previous studies have revealed that Cu metabolism plays an important role in the development of KRAS-driven tumors. In this study, we revealed the therapeutic value of the Cu ionophore elesclomol (ES) for treating KRAS G12 -mutant–driven lung adenocarcinoma. KRAS G12 -mutant lung adenocarcinoma cells relied on the Cu exporter ATP7A to maintain Cu homeostasis. ES induced cellular Cu accumulation and cuproptosis by upregulating the expression of the E3 ligase OSTM1, which interacted with the IRGY motif of ATP7A to promote ubiquitination and degradation. KRAS G12D transgenic mice and lung cancer organoids derived from the mice were used to validate the therapeutic effects of ES and Cu in vivo and in vitro . These findings indicate that KRAS G12 -driven lung adenocarcinoma relies on ATP7A-mediated Cu metabolic homeostasis, which can be perturbed with ES as an effective treatment strategy. Significance: The copper ionophore elesclomol is effective for treating KRAS-driven lung cancer by activating the OSTM1-ATP7A regulatory axis to perturb copper metabolism homeostasis.
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ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Yue Wang,Chengli Xie,Yike Huang,Kai Zhou,Zhining Xia
Molecular crowding, as a crucial mechanism for regulating intermolecular interactions, has demonstrated significant application potential in materials science in recent years. This study proposes and systematically explores the enhancement effect and underlying mechanism of molecular crowding on the adsorption performance of paracetamol molecularly imprinted polymers (AMIP). By introducing glucose as a molecular crowding agent into the adsorption system of AMIP for paracetamol (APAP), the correlation between the physical parameters of the solution microenvironment and the adsorption capacity of AMIP was elucidated through nuclear magnetic resonance (NMR) transverse relaxation time and diffusion-ordered spectroscopy (DOSY) analyses. Experimental results reveal that the crowding effect emerges when the glucose concentration exceeds 10 g/L. At a glucose concentration of 500 g/L, the adsorption capacity of AMIP increases to 1.96 times that under nonmolecular crowding conditions. The primary mechanism originates from the compression of the solution’s free volume by glucose through the excluded volume effect, significantly increasing the local effective concentration of APAP. Secondarily, glucose competitively binds a large number of water molecules, altering the polar microenvironment of water and weakening the hydrogen bonding between APAP and water, thereby facilitating the specific binding of APAP to AMIP. To validate the mechanism, adsorption studies on MIPs for four compounds with distinct polarities confirmed that molecular crowding enhances the adsorption capacities of both hydrophilic and hydrophobic compounds. This work provides a novel solution microenvironment strategy for optimizing MIP performance and expands the application potential of molecular crowding in the rational design of functional materials.
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ACS Food Science & Technology
·
2025
·
IF 2.8
Jun-Hui Du,Yu-Yun Xiao,Ying-Chao Guo,Wen-Qing Zhang,Guan-Ru Si,Zheng-Fang Wu,Chuan-Qiang Gao,Jie Mei,Yi-Long Ma,Zhao-Jun Wei
T2DM (Type 2 diabetes mellitus) is a chronic metabolic disease typically managed with medications that often cause undesirable side effects, highlighting the urgent need for safe and effective natural alternatives. In this study, Baijiu distillers’ grains (BDGs) from Xiaojiao Baijiu were used to screen and identify anti-α-glucosidase peptides. The fraction under 3 kDa of the hydrolyzate generated by alcalase demonstrated the most potent inhibitory activity. This fraction was subsequently separated by RP-HPLC, resulting in the most effective subfraction, F2–2, with an inhibitory rate of 77.33 ± 1.15%. Six potential antidiabetic peptides (AAPFYAL, LAYPQ, IRLPFNQI, INPALPW, ATPVFL, SSSSAVVG) were identified from F2–2, with AAPFYAL showing the highest inhibitory activity (IC50 = 363.77 μM). Molecular docking demonstrated that these peptides competitively bind to key residues of α-glucosidase (such as D327, D542) via hydrogen bonds, which was further confirmed by pharmacophore model analysis. Our findings demonstrate that Xiaojiao BDGs are promising hypoglycemic resources.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jingjing Zhu,Jiayi Pan,Zhiting Wu,Yong Han,Wenxiao Wang,Lingyan Liu,Guang Yang,Tao Yi
The central paradigm in cancer chemotherapy revolves around expanding the therapeutic window: maximizing antitumor potency while minimizing off-target toxicity. Conventional drug delivery methods for superficial tumors (such as systemic and intratumoral injections) suffer from several limitations, including inefficient drug delivery and off-target toxicity. In contrast, the activated-prodrug strategy can significantly address the drawbacks associated with conventional chemotherapeutic agents. These improvements include reducing systemic toxicity, enhancing tumor targeting, and improving drug solubility, thereby offering transformative perspectives for optimizing conventional chemotherapy. However, current prodrug systems remain constrained by rapid systemic elimination, necessitating frequent administration. Thus, novel strategies need to be developed to enhance prodrug delivery. Microneedles (MNs) represent a promising therapeutic platform for precise and controllable drug delivery, particularly in the management of superficial tumors. In this study, we propose an MN drug delivery system for the transdermal administration of reactive oxygen species (ROS)-activated prodrug (FDOCl-19), facilitating in situ drug delivery and selective chemotherapy. Our results establish that this FDOCl-19-loaded MN (FDOCl-19@MN) elicits tumor cell apoptosis in vitro. In mouse models of subcutaneous melanoma, FDOCl-19@MN significantly promoted tumor regression with minimal systemic toxicity, demonstrating favorable biosafety. Collectively, this work establishes FDOCl-19@MN as a transdermal theranostic platform featuring minimally invasive MNs that deliver ROS-activated prodrugs (FDOCl-19) for spatiotemporally controlled treatment of superficial tumors.
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Small Methods
·
2025
·
IF 9.1
Jin-Hua Liu,Yuze Sun,Zhihan Gao,Wen-Hua Yang,Lingyun Li,Zheng Wei,Wenpeng Han,Ru Li,Jun Zhang,Yun-Ze Long
High-entropy spinel oxides (HEOs) offer a promising route to overcome the kinetic bottleneck of the oxygen evolution reaction (OER) through synergistic multi‑metal interactions, lattice distortion, and tailored electronic structures. Here, the fabrication of a quinary FeCoNiCrMo spinel oxide nanofiber via electrospinning and controlled calcination is reported. Incorporation of Mo serves to modulate the local crystal field and electronic spin states, while application of an external magnetic field enhances spin polarization of reaction intermediates, lowering the energy barrier for triplet O 2 formation. The optimized HEO exhibits an overpotential of 240 mV at 10 mA cm − 2 and a Tafel slope of 45 mV·dec −1 under a 400 mT magnetic field, outperforming most reported high‑entropy catalysts. Density functional theory (DFT) and in situ Raman spectroscopy reveal that magnetic-field-assisted spin filtering accelerates O─O bond formation via a spin‑aligned dual‑site mechanism. Assembling HEO with Pt/C in a two‑electrode electrolyzer achieves overall water splitting at 10 mA·cm −2 with a cell voltage of 1.565 V and near 100% Faradaic efficiency. This work demonstrates the powerful synergy of high‑entropy design and magnetic spin control, offering a fresh strategy for high‑performance water‑splitting electrocatalysts.
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ANALYTICAL LETTERS
·
2025
·
IF 1.8
Yi Zhang,Jiali Lu,Jiaxiong Zhao,Genrong Li,Shuai Li
This study presents an efficient and highly sensitive method for detecting Rhodamine B and 6 G in complex food matrices. A dual microextraction approach combining electromembrane extraction (EME) and magnetic solid-phase extraction (MSPE) was applied, followed by analysis using high-performance liquid chromatography with fluorescence detection (HPLC-FLD). Critical parameters—such as donor and acceptor phase pH, applied voltage, membrane solvent, extraction time, sorbent dosage, adsorption duration, and elution conditions—were systematically optimized to ensure reliable and reproducible performance. The method showed excellent linearity (1.0–200 ng/mL; R2 = 0.9987 for Rhodamine B and 0.9983 for Rhodamine 6 G), with detection limits of 0.9 ng/mL and 1.2 ng/mL, respectively. Recoveries ranged from 92.1% to 101.9% with relative standard deviations (RSDs) below 5%. Application to real food samples—including spicy strips, candies, and chili oil-based bean snacks—confirmed the method’s accuracy and strong matrix tolerance. Compared to conventional microextraction-chromatographic techniques, this method offers notable advantages in speed, sensitivity, and broad applicability. It is a powerful tool for rapid screening and regulatory monitoring of illicit synthetic dyes in food.
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Catalysts
·
2025
·Vol. 15
·期 10
·952
·
IF 4
Ling Xu,Shuang Zhang,Hui Xu,Anzhou Ma,Guoqiang Zhuang,Shuhao Huo,Bin Zou,Jingya Qian,Guoqiang Guan,Feng Wang
Tetracycline antibiotics are widely used, but their resistance to degradation and persistence in the environment pose a potential risk of inducing antibiotic resistance, creating significant threats to both the environment and human health. This study established a laccase–mediator system (LMS) using natural green tea polyphenols (GTPs) as mediators for efficient tetracycline degradation. Through analyzing the main GTP components and optimizing the reaction conditions, the degradation efficiency of the system was evaluated. The experimental results indicated that, among the various tea polyphenol components, epicatechin gallate (ECG) contributed the most significantly to the degradation efficiency. Under optimized conditions, the Lac-ECG system degraded over 98% of tetracycline within 3–4 min. Further optimization of the Lac-GTP system allowed us to identify the following optimal conditions: a GTP concentration of 1.0 mmol/L, laccase concentration of 1.0 mg/mL, pH of 6.0, and temperature of 25 °C. Under these conditions, a degradation rate of 95.07% was attained within 5 min, outperforming a system using the synthetic mediator ABTS. Additionally, metal ions such as Ca2+, Mg2+, Cu2+, Fe3+, Fe2+, and Ni2+were found to enhance the degradation process, while Mn2+and Hg2+exhibited inhibitory effects. Antibacterial activity tests revealed that the degradation products completely lost their antimicrobial activity, demonstrating effective detoxification of tetracycline. In conclusion, the tea polyphenol-based laccase–mediator system developed in this study exhibits high efficiency, cost-effectiveness, and environmental friendliness, offering a promising strategy for the remediation of tetracycline-contaminated environments.
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Polymers
·
2025
·Vol. 17
·期 21
·2904
·
IF 4.9
Shiyi Ming,Piao Wang,Shaoyuan Wu,Jinghan Hu,Jie Zhang,Lianlian Li,Bingyue Huang,Weijiang Huang,Xingyu Guan,Kui Wang,Wei Yan
The morphology and composition of inorganic particles play a vital role in controlling the flame-retardant characteristics of polymers. Halogen-free flame-retardant polymers have also become a current research hotspot. Boron nitride (BN), phytic acid (PA), and chitosan (CS), a natural polysaccharide with a nitrogen content of approximately 6.8–7.5%, show great promise as flame retardants owing to their high thermal stability, P-based flame retardancy, and natural polysaccharide properties, respectively. In this study, BN (BN@PA-CS) particles coated with PA and CS were designed and prepared via a facile modification strategy. The effect of BN@PA-CS on the mechanical and flame-retardant properties of polyvinylidene fluoride (PVDF) was further investigated, and it was found that both characteristics were improved. Compared to pure PVDF, the PVDF composite films exhibited a significantly lower peak heat release rate and total heat release. With a BN@PA-CS content of 20%, the peak was the lowest at 18.25 W/g, corresponding to a decrease of 77.83%. This phenomenon may be attributed to the synergistic effect of the BN nanosheets and PA-CS in the BN@PA-CS particles. This work describes a facile and effective method of modifying the morphology and composition of inorganic particles, thereby controlling the properties of polymers, and provides a new approach to improving the safety of PVDF battery separators.
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