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Mechanical strength and biomechanics of extracellular vesicles 细胞外囊泡的机械强度和生物力学
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-27 DOI: 10.1016/j.nantod.2025.102905
Yuewen Zhai , Ji Fang , Fang He , Ziyuan Qin , Jun Liu , Siwen Li
Extracellular vesicles (EVs) serve as essential mediators of intercellular communication and play a pivotal role in both physiological and pathological processes. Their mechanical strength and biomechanical properties not only dictate structural stability, in vivo delivery efficiency, and biological functionality but also have significant implications for disease diagnosis and targeted therapy. This review systematically summarizes the methodologies and key parameters used to assess the mechanical strength of EVs, and synthesizes current evidence identifying the internal protein network, membrane cholesterol and phospholipid composition, AQP1 and other membrane protein expression levels, and vesicle size differences as primary structural determinants of EV elasticity. Furthermore, the physiological state of the source cells, production processes, and external mechanical forces are also recognized as critical factors shaping EV mechanical properties. In addition, this review comprehensively discusses the adaptive behaviors of EVs with distinct mechanical characteristics in complex biological environments, with a particular focus on their transmembrane transport, circulation dynamics, and targeted delivery capabilities, and delineates the mechanistic principles by which EVs with varying elasticity achieve prolonged circulation and subsequent uptake by recipient cells. Based on recent advances, this review also explores the potential applications of the mechanical properties and biomechanical principles of EVs in quality control assessment, disease diagnostics, and drug delivery, while offering a forward-looking perspective on their future development in the biomedical field.
细胞外囊泡(EVs)是细胞间通讯的重要媒介,在生理和病理过程中都起着关键作用。它们的机械强度和生物力学特性不仅决定了结构稳定性、体内递送效率和生物功能,而且对疾病诊断和靶向治疗具有重要意义。本文系统总结了评估EV机械强度的方法和关键参数,并综合了现有证据,证明内部蛋白质网络、膜胆固醇和磷脂组成、AQP1和其他膜蛋白表达水平以及囊泡大小差异是EV弹性的主要结构决定因素。此外,源细胞的生理状态、生产过程和外部机械力也被认为是影响电动汽车力学性能的关键因素。此外,本文还全面讨论了具有不同机械特性的电动汽车在复杂生物环境中的适应性行为,特别关注它们的跨膜运输、循环动力学和靶向递送能力,并描述了具有不同弹性的电动汽车实现长时间循环和随后被受体细胞吸收的机制原理。本文综述了电动汽车的力学特性和生物力学原理在质量控制评价、疾病诊断和给药等方面的潜在应用,并对其在生物医学领域的发展前景进行了展望。
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引用次数: 0
Dual-responsive glucose/pH degradable nanozyme hydrogel with cascade catalytic antibacterial performance for infected diabetic wound treatment 具有级联催化抗菌性能的双响应葡萄糖/pH可降解纳米酶水凝胶用于糖尿病感染伤口治疗
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-27 DOI: 10.1016/j.nantod.2025.102906
Shuang Zhao , Wujie Guo , Guoye Yang , Peng Hu , Yidi Liu , Liang Chen , Shiping Ning , Xiaoying Cao , Yanfei Pan , Jiahua Shi , Wei Jiang , Decheng Lu , Huiqiao Huang
Diabetic wound infections often lead to excessive inflammation, resulting in chronic or non-healing wounds. Effectively addressing the unique characteristics of the wound microenvironment for precise and safe treatment remains a significant challenge. In this work, we report the construction of novel, capsule-like natural glucose oxidase (GOx)-loaded metal-phenolic nanozymes (GOx-Zn2+/Cu2+-TA-VOx, GZ-TA-VOx), which is anchored to a pH/glucose dual-responsive degradable hydrogel composed of poly(vinyl alcohol) (PVA) and phenylboronic-acid-grafted sodium alginate (SA-PBA) for managing bacterial infections in diabetic wounds. The GZ-TA-VOx nanozymes exhibit efficient peroxidase (POD)-like and glutathione peroxidase (GPx)-like activities, as well as photothermal antibacterial properties. Additionally, the GOx in GZ-TA-VOx consumes glucose, producing hydrogen peroxide (H2O2) and gluconic acid, which ameliorates hyperglycemia at the wound site and enhances the catalytic activity of the GZ-TA-VOx nanozymes. Encapsulation in a PVA/SA-PBA hydrogel provides tissue adhesion, self-healing, and degradable properties, enabling controlled drug release and synergistic effects for enhanced wound healing. In vivo experiments demonstrated that the GZ-TA-VOx hydrogel effectively alleviated inflammation, promoted angiogenesis and epithelial cell proliferation, and facilitated wound recovery, highlighting its potential for managing diabetic wounds. Overall, this work introduces a new synthesis approach for metal-phenolic nanozymes and presents a promising strategy for treating bacterial-infected diabetic wounds.
糖尿病性伤口感染往往导致过度炎症,导致慢性或不愈合的伤口。有效地解决伤口微环境的独特特征,以实现精确和安全的治疗仍然是一个重大挑战。在这项工作中,我们报道了一种新型的、胶囊状的天然葡萄糖氧化酶(GOx)负载金属-酚纳米酶(GOx- zn2 +/Cu2+-TA-VOx, GZ-TA-VOx)的构建,它被固定在pH/葡萄糖双响应的可降解水凝胶上,该水凝胶由聚乙乙醇(PVA)和苯硼酸接枝海藻酸钠(SA-PBA)组成,用于治疗糖尿病伤口的细菌感染。GZ-TA-VOx纳米酶表现出高效的过氧化物酶(POD)样和谷胱甘肽过氧化物酶(GPx)样活性,以及光热抗菌性能。此外,GZ-TA-VOx中的GOx消耗葡萄糖,产生过氧化氢(H2O2)和葡萄糖酸,从而改善伤口部位的高血糖,并增强GZ-TA-VOx纳米酶的催化活性。包封在PVA/SA-PBA水凝胶中提供组织粘附、自我修复和可降解特性,使药物释放可控,协同作用增强伤口愈合。体内实验表明,GZ-TA-VOx水凝胶可有效减轻炎症,促进血管生成和上皮细胞增殖,促进伤口恢复,突出了其治疗糖尿病伤口的潜力。总之,这项工作介绍了一种新的金属酚纳米酶的合成方法,并为治疗细菌感染的糖尿病伤口提供了一个有前途的策略。
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引用次数: 0
New insights into therapeutic strategies against Zika virus from virus–host interactions 病毒-宿主相互作用对寨卡病毒治疗策略的新见解
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-22 DOI: 10.1016/j.nantod.2025.102902
Qiqi Li , Yuhan Dong , Zehong Chen , Hui Zhang , Zengming Wang , Nan Liu , Mei Lu , Wei Zhu , Haonan Xing , Aiping Zheng
Global climate change has created favorable conditions for the transmission and expansion of the Zika virus (ZIKV), with the risk of ZIKV re-emergence posing an ongoing biosecurity threat. However, the lack of effective anti-Zika drugs makes the clinical application of symptom-relieving therapies the only available option. Recent progress in understanding virus–host interactions has significantly accelerated the development of innovative antiviral strategies against ZIKV infection. This review examines the challenges encountered in the development of anti-ZIKV drugs and explores potential therapeutic strategies through a novel ZIKV–host interaction perspective. Moreover, this review systematically outlines novel anti-ZIKV drug strategies, including promising molecular mechanisms and potential targets derived from ZIKV, replication-associated host factors, and immune system elements for drug design. Targeting ZIKV structural components to disrupt its life cycle remains a conventional antiviral strategy, while targeting replication-associated host factors and developing drugs that modulate host cellular processes represent promising therapeutic approaches. The frequently neglected antagonistic effect of ZIKV on innate host immunity and corresponding antiviral strategies are also examined in this review. More importantly, recent progress in antiviral strategies during pregnancy and anti-ZIKV drug delivery strategies are examined, with a focus on potential challenges and future directions for anti-Zika drugs. Further, regulating key placental blood barrier targets represents a promising therapeutic strategy against ZIKV during pregnancy. The progress of anti-ZIKV drug delivery systems enable maximum therapeutic efficacy. This review proposes an integration of potential intervention strategies from the perspective of ZIKV–host interactions, thereby aiming to establish a foundation for future anti-ZIKV research while accelerating the translation of anti-ZIKV therapeutics into clinical practice.
全球气候变化为寨卡病毒(ZIKV)的传播和扩展创造了有利条件,寨卡病毒再次出现的风险构成了持续的生物安全威胁。然而,由于缺乏有效的抗寨卡病毒药物,临床应用缓解症状的疗法是唯一可行的选择。最近在了解病毒-宿主相互作用方面取得的进展大大加快了针对寨卡病毒感染的创新抗病毒策略的开发。本文综述了抗寨卡病毒药物开发中遇到的挑战,并从新的寨卡病毒与宿主相互作用的角度探讨了潜在的治疗策略。此外,本综述系统地概述了新的抗寨卡病毒药物策略,包括有希望的分子机制和来自寨卡病毒的潜在靶点、复制相关宿主因子和用于药物设计的免疫系统元素。靶向ZIKV结构成分破坏其生命周期仍然是一种传统的抗病毒策略,而靶向复制相关宿主因子和开发调节宿主细胞过程的药物是有希望的治疗方法。本综述还探讨了ZIKV对先天宿主免疫的经常被忽视的拮抗作用和相应的抗病毒策略。更重要的是,研究了妊娠期抗病毒策略和抗寨卡病毒药物递送策略的最新进展,重点讨论了抗寨卡病毒药物的潜在挑战和未来方向。此外,调节关键的胎盘血液屏障靶点是妊娠期间对抗寨卡病毒的一种有希望的治疗策略。抗寨卡病毒药物递送系统的进展使治疗效果最大化。本文从寨卡病毒与宿主相互作用的角度提出了一种整合潜在干预策略的方法,旨在为未来的抗寨卡病毒研究奠定基础,同时加速抗寨卡病毒治疗方法转化为临床实践。
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引用次数: 0
Aerogels as next-generation electrocatalysts for water electrolysis and beyond 气凝胶作为水电解及其他领域的下一代电催化剂
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-17 DOI: 10.1016/j.nantod.2025.102901
Balamurugan Muthukutty , Ponnaiah Sathish Kumar , Jun-Hyung Im , Periakaruppan Prakash , Daeho Lee , Young-Ki Kim
The rising energy demand and depletion of conventional fuels have led to intensified interest in water-splitting as a sustainable clean energy resolution. Accordingly, developing efficient catalytic materials have become vital for advancing key electrochemical processes, including the oxygen evolution reaction (OER), hydrogen evolution reaction (HER), and overall water electrolysis, which are essential for energy conversion technologies (e.g., metal-air batteries, fuel cells, and water-splitting devices). Given the need for innovative solutions in this domain, aerogel (AG)-based materials have emerged as leading candidates, distinguished by their highly porous microstructure, tunable properties, and diverse synthesis approaches. The goal of this review is to offer a thorough examination of AG catalysts, elucidating why they are pivotal for addressing current challenges in electrocatalysis. We explore their synthesis techniques, structural characterization methods, and roles in enhancing electrochemical kinetics and electrode activity. The discussion extends to their ability to lower overpotentials, boost catalytic performance, and prolong cycle life, making them indispensable for sustainable energy applications. Furthermore, the incorporation of Density Functional Theory (DFT) as a computational tool provides deeper insights into molecular pathways and reaction mechanisms in water-splitting, strengthening the connection between experimental and theoretical studies. Finally, this review identifies future directions and addresses the challenges in developing cost-effective, high-efficiency AG-based catalysts, underscoring their potential to transform clean energy production.
能源需求的增加和传统燃料的枯竭使人们更加关注将水分解作为一种可持续的清洁能源解决方案。因此,开发高效的催化材料对于推进关键的电化学过程至关重要,包括析氧反应(OER),析氢反应(HER)和整体水电解,这对于能量转换技术(例如金属-空气电池,燃料电池和水分解装置)至关重要。考虑到该领域对创新解决方案的需求,气凝胶(AG)基材料已成为领先的候选材料,其特点是其高度多孔的微观结构、可调的性能和多种合成方法。本综述的目的是对AG催化剂进行全面的研究,阐明为什么它们对解决当前电催化领域的挑战至关重要。我们探讨了它们的合成技术、结构表征方法以及在提高电化学动力学和电极活性方面的作用。讨论扩展到它们降低过电位、提高催化性能和延长循环寿命的能力,使它们成为可持续能源应用中不可或缺的材料。此外,结合密度泛函理论(DFT)作为计算工具,可以更深入地了解水分解的分子途径和反应机制,加强实验和理论研究之间的联系。最后,本综述确定了未来的发展方向,并解决了开发成本效益高、效率高的ag基催化剂的挑战,强调了它们改变清洁能源生产的潜力。
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引用次数: 0
Antifouling zwitterionic coating enhances electrochemical aptamer-based sensors for therapeutic drug monitoring 防污两性离子涂层增强了用于治疗药物监测的电化学适体传感器
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-16 DOI: 10.1016/j.nantod.2025.102892
Haowei Duan , Shuhua Peng , Shuai He , Shi-Yang Tang , Keisuke Goda , Chun H. Wang , Ming Li
Electrochemical aptamer-based (E-AB) sensors have experienced remarkable growth across a broad range of applications, such as precision medicine, chronic disease management, food safety, and environmental monitoring, due to their exceptional capability for real-time and continuous monitoring of biomarkers. However, biofouling in complex biological environments remains a critical challenge for the E-AB sensors, compromising signal strength, operational stability, and biosensing specificity. Here, we present a zwitterionic coating strategy that integrates poly-sulfobetaine methacrylate (SBMA) and polydopamine (PDA) to enhance the antifouling properties of the E-AB sensors, thereby enabling sensitive, stable, and accurate detection of a model antibiotic drug, vancomycin. The durable and hydrophilic antifouling layer was grafted onto the electrode surface to minimize signal drift while preserving sufficient signal on the E-AB sensors. The SBMA@PDA coating was systematically optimized and demonstrated superior resistance to biofouling under various environmental conditions, including pH, temperature, and mechanical stress. Furthermore, the coating was incorporated into a wearable microneedle patch for monitoring vancomycin dynamics in artificial interstitial fluids, achieving robust stability and performance. These findings establish a reliable and effective antifouling approach, advancing the practical application of E-AB sensors for continuous therapeutic drug monitoring in clinical and wearable healthcare settings.
基于电化学适配体(E-AB)的传感器由于具有实时和连续监测生物标志物的卓越能力,在精准医疗、慢性疾病管理、食品安全和环境监测等广泛应用中取得了显着增长。然而,复杂生物环境中的生物污垢仍然是E-AB传感器面临的一个关键挑战,它会影响信号强度、运行稳定性和生物传感特异性。在这里,我们提出了一种两性离子涂层策略,该策略集成了聚甲基丙烯酸磺基甜菜碱(SBMA)和聚多巴胺(PDA),以增强E-AB传感器的防污性能,从而实现对模型抗生素万古霉素的敏感、稳定和准确检测。在电极表面接枝了耐用且亲水的防污层,以减少信号漂移,同时保持E-AB传感器上足够的信号。对SBMA@PDA涂层进行了系统优化,并在各种环境条件下(包括pH、温度和机械应力)表现出优异的抗生物污染能力。此外,该涂层被纳入可穿戴微针贴片中,用于监测人工间质液中万古霉素的动态,获得了强大的稳定性和性能。这些发现建立了一种可靠有效的防污方法,推进了E-AB传感器在临床和可穿戴医疗保健环境中持续治疗药物监测的实际应用。
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引用次数: 0
The landscape of nanomedical clinical trials 纳米医学临床试验的前景
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-15 DOI: 10.1016/j.nantod.2025.102898
Evin Gultepe, Raghnya Valluru, Nik Bear Brown, Srinivas Sridhar
Nanotechnology has transformed healthcare, leading to the clinical adoption of numerous nanomedical products. To evaluate their clinical translation, we analyzed all trials registered on ClinicalTrials.gov using a novel nanomedicine lexicon developed through expert curation and generative AI. This approach identified 4114 nanomedical clinical trials (out of more than 500,000) forming the Nanomedical Clinical Trials (NanoCT) dataset. Our analysis reveals a 38 % rise in nanomedical trials in recent years. While oncology remains dominant (30 %), emerging applications—particularly in infectious diseases, driven by the rise of mRNA vaccines—demonstrate the field’s expanding therapeutic scope. This diversification is further evidenced by the growing use of micelles, polymeric, and metallic nanoparticles, marking a shift from the dominance of liposomal formulations. Despite significant advancements, nanomedical trials account for only 0.8 % of all registered clinical trials, highlighting key translational challenges such as regulatory complexities, high production costs, and clinical design limitations. Addressing these barriers requires the establishment of a universally accepted nanomedical lexicon to enhance data harmonization, streamline regulatory pathways, and improve interdisciplinary communication. This comprehensive analysis provides critical insights into the trajectory of nanohealth, identifies obstacles to clinical translation, and outlines strategies to maximize its future impact in medicine.
纳米技术已经改变了医疗保健,导致许多纳米医疗产品的临床应用。为了评估他们的临床翻译,我们使用由专家策展和生成式人工智能开发的新型纳米医学词典分析了ClinicalTrials.gov上注册的所有试验。该方法确定了4114项纳米医学临床试验(超过500,000项),形成了纳米医学临床试验(NanoCT)数据集。我们的分析显示,近年来纳米医学试验增加了38% %。虽然肿瘤仍占主导地位(30% %),但新兴应用——特别是在传染病方面,受mRNA疫苗兴起的推动——表明该领域的治疗范围正在扩大。胶束、聚合物和金属纳米颗粒的使用越来越多,这进一步证明了这种多样化,标志着脂质体配方的主导地位的转变。尽管取得了重大进展,但纳米医学试验仅占所有注册临床试验的0.8% %,突出了关键的转化挑战,如监管复杂性、高生产成本和临床设计限制。解决这些障碍需要建立一个普遍接受的纳米医学词典,以加强数据协调,简化监管途径,并改善跨学科交流。这项综合分析为纳米健康的发展轨迹提供了关键的见解,确定了临床转化的障碍,并概述了最大化其未来在医学中的影响的策略。
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引用次数: 0
Sonodynamic biodegradable pseduo-conjugate polymer delivery of warfarin for inducing generation of cancerous ROS and ferroptosis 声动力可生物降解的伪共轭聚合物递送华法林诱导癌变ROS的产生和铁下垂
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-13 DOI: 10.1016/j.nantod.2025.102891
Pengchen Wang , Jintong Na , Xiyu Liu , Minhui Cui , Ganghao Liang , Xinyue He , Haihua Xiao , Yongxiang Zhao , Yuan Liao , Liping Zhong
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by low immune response rates and high recurrence. This underscores an urgent need for more effective treatment strategies for liver cancer patients. Ferroptosis, a type of cell death associated with iron-dependent lipid peroxidation, has shown significant potential in HCC treatment. However, the efficacy of this monotherapy for tumor treatment remains limited. Enhancing reactive oxygen species (ROS) accumulation and lipid peroxide formation by inhibiting the tumor cell antioxidant system has emerged as a promising anti-tumor strategy. In this study, we developed a nanoplatform, NP (nanoparticle)-BSD@WFR, specifically tailored for HCC treatment. This system combines a biodegradable sonodynamic polymer (BSD) with warfarin (WFR), a VKORC1L1 inhibitor that prevents intracellular peroxide elimination and enhances ferroptosis. Under ultrasound irradiation, NP-BSD@WFR generates ROS and releases WFR, directly targeting cancer cells. Concurrently, ROS and WFR synergistically enhance lipid peroxide production in cancer cells, triggering ferroptosis and activating the immune system. Animal studies further demonstrate that combining sonodynamic therapy with WFR-induced ferroptosis produces a synergistic anti-tumor effect, promoting a strong immune response in vivo. This study introduces an innovative therapeutic approach combining sonodynamic therapy and WFR for HCC treatment and highlights its promising efficacy.
肝细胞癌(HCC)是最常见的原发性肝癌类型,其特点是免疫应答率低,复发率高。这强调了对肝癌患者更有效的治疗策略的迫切需要。铁下垂是一种与铁依赖性脂质过氧化相关的细胞死亡,在HCC治疗中显示出巨大的潜力。然而,这种单一疗法对肿瘤的治疗效果仍然有限。通过抑制肿瘤细胞抗氧化系统促进活性氧(ROS)的积累和脂质过氧化形成已成为一种很有前景的抗肿瘤策略。在这项研究中,我们开发了一种纳米平台NP(纳米颗粒)-BSD@WFR,专门用于HCC治疗。该系统结合了可生物降解的声动力聚合物(BSD)和华法林(WFR),华法林是一种VKORC1L1抑制剂,可防止细胞内过氧化物消除并增强铁凋亡。在超声照射下,NP-BSD@WFR产生ROS,释放WFR,直接靶向癌细胞。同时,ROS和WFR协同增强癌细胞中脂质过氧化产物,引发铁下垂,激活免疫系统。动物研究进一步表明,声动力治疗与wfr诱导的铁下垂联合治疗可产生协同抗肿瘤作用,促进体内强烈的免疫应答。本研究介绍了一种结合声动力疗法和白细胞fr治疗HCC的创新治疗方法,并强调了其良好的疗效。
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引用次数: 0
Nanotechnology for diagnosis and therapy of idiopathic pulmonary fibrosis: Recent advances and future perspectives 纳米技术用于特发性肺纤维化的诊断和治疗:最新进展和未来展望
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-12 DOI: 10.1016/j.nantod.2025.102889
Chenyu Zhao , Ao Xiao , Chen Chen , Wei Mu , Wen-Yang Li , Lingqian Chang
Idiopathic pulmonary fibrosis (IPF) is a highly progressive interstitial lung disease characterized by alveolar epithelial cell damage, extracellular matrix deposition, and irreversible lung parenchymal scarring, ultimately leading to fatal respiratory failure. Early diagnosis and effective intervention of IPF are crucial for improving its prognosis and reducing mortality. Current diagnostic methods for early-stage IPF rely on high-resolution CT, histopathological examination, and multidisciplinary discussions. However, these approaches have significant limitations, including poor accuracy, invasiveness, and being time-consuming, which often delays therapeutic intervention. Furthermore, existing pharmacotherapy offer only limited efficacy in slowing disease progression due to the low bioavailability and limited delivery efficiency. To address these challenges in diagnostics and therapeutics, nanotechnology-mediated solutions have emerged as promising approaches. Contemporary advancement focuses on three domains: (1) development of functionalized nano-contrast agents, nanoprobe- and nanoparticle-based biosensor platforms for in vivo and in vitro precision diagnostics, (2) design of nanocarriers for inhalable drug delivery to enhance therapeutic efficacy, and (3) integrated nanoplatforms enabling simultaneous therapeutic delivery and real-time monitoring for targeted intervention. Overall, this review summarized recent advancements in nanotheranostic applications for the diagnosis and therapy of IPF. Moving forward, future research prioritize overcoming translational barriers to facilitate clinical implementation.
特发性肺纤维化(IPF)是一种高度进行性肺间质性疾病,其特征是肺泡上皮细胞损伤、细胞外基质沉积和不可逆的肺实质瘢痕形成,最终导致致命的呼吸衰竭。IPF的早期诊断和有效干预是改善其预后和降低死亡率的关键。目前早期IPF的诊断方法依赖于高分辨率CT、组织病理学检查和多学科讨论。然而,这些方法有明显的局限性,包括准确性差、侵入性和耗时,这往往会延迟治疗干预。此外,由于低生物利用度和有限的递送效率,现有的药物治疗在减缓疾病进展方面的疗效有限。为了解决诊断和治疗中的这些挑战,纳米技术介导的解决方案已经成为有希望的方法。当前的进展主要集中在三个领域:(1)开发功能化纳米造影剂、纳米探针和纳米颗粒为基础的生物传感器平台,用于体内和体外精确诊断;(2)设计可吸入药物递送的纳米载体,以提高治疗效果;(3)集成纳米平台,使治疗递送和实时监测靶向干预成为可能。综上所述,本文综述了近年来纳米治疗在IPF诊断和治疗中的应用进展。展望未来,未来的研究将优先考虑克服翻译障碍,以促进临床应用。
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引用次数: 0
Pulmonary delivery of dynamic size-switching microspheres for regulation of neutrophils and macrophages in the acute respiratory distress syndrome 急性呼吸窘迫综合征中肺输送动态大小开关微球对中性粒细胞和巨噬细胞的调节
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-12 DOI: 10.1016/j.nantod.2025.102894
Xiangjun Ou , Xiong Liu , Qi Qiao , Xiaonan Li , Zhangxi Xu , Tianyi Tian , Yang Li , Ling Tang , Tianzi Shi , Li Kong , Zhiping Zhang
Modulation of the interaction between neutrophils and macrophages is pivotal for controlling the inflammatory response in acute respiratory distress syndrome (ARDS). To enhance pulmonary drug deposition efficiency and simultaneously regulate macrophages and neutrophils, dynamic size-switching microsphere complexes (DNMP) were synthesized based on a double emulsion formulation strategy, utilizing acetalated dextran (Ac-Dextran) as the matrix material and co-encapsulated roflumilast-loaded albumin nanoparticles (BNP) and dexamethasone (DEX). DNMP exhibited high uniformity and encapsulation efficiency. Upon pulmonary administration, the micron-sized DNMP demonstrated remarkable deposition efficiency in the lungs, with a pulmonary retention time exceeding 48 h. Within the acidic microenvironment of inflamed lung, DNMP rapidly disintegrated, thereby releasing the co-encapsulated BNP and DEX. The BNP exhibited specific targeting towards neutrophils, subsequently releasing roflumilast to exert potent anti-inflammatory effects. Meanwhile, DEX modulated macrophage polarization and the overall inflammatory microenvironment, thereby contributing to a comprehensive and synergistic therapeutic strategy for mitigating pulmonary inflammation. As expected, DNMP alleviated lung injury by reducing neutrophil infiltration, decreasing the proportion of pro-inflammatory M1-like macrophages, suppressing inflammatory cytokine and ROS levels, and inhibiting neutrophil extracellular traps (NETs) formation. This innovative acid-responsive dual-drug delivery system provided a promising therapeutic strategy for ARDS.
调节嗜中性粒细胞和巨噬细胞之间的相互作用是控制急性呼吸窘迫综合征(ARDS)炎症反应的关键。为了提高肺部药物沉积效率,同时调节巨噬细胞和中性粒细胞,以乙酰化右旋糖酐(Ac-Dextran)为基质材料,以负载罗氟米拉斯特的白蛋白纳米颗粒(BNP)和地塞米松(DEX)共包被,采用双乳配方策略合成了动态大小切换微球复合物(DNMP)。DNMP具有较高的均匀性和包封效率。经肺给药后,微米大小的DNMP在肺中表现出显著的沉积效率,肺滞留时间超过48 h。在炎症肺的酸性微环境中,DNMP迅速分解,释放出共包被的BNP和DEX。BNP表现出对中性粒细胞的特异性靶向,随后释放罗氟司特发挥有效的抗炎作用。同时,DEX调节巨噬细胞极化和整体炎症微环境,从而为减轻肺部炎症提供了全面和协同的治疗策略。正如预期的那样,DNMP通过减少中性粒细胞浸润、降低促炎m1样巨噬细胞比例、抑制炎症细胞因子和ROS水平、抑制中性粒细胞胞外陷阱(NETs)形成来减轻肺损伤。这种创新的酸反应性双药给药系统为ARDS提供了一种很有前景的治疗策略。
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引用次数: 0
Electronic cloud-regulation strategy enabling rapid and sensitive near-infrared detection of ONOO⁻ for dynamic monitoring of ferroptosis-mediated drug-induced liver injury 电子云调节策略,实现ONOO的快速和灵敏的近红外检测,用于动态监测铁中毒介导的药物性肝损伤
IF 10.9 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2025-09-12 DOI: 10.1016/j.nantod.2025.102900
Yongchuang Li , Haiyue Liu , Yuru Liu , Shaowei Wang , Caixia Yin , Fangjun Huo
Drug-induced liver injury (DILI) is caused by hepatotoxic effects resulting from drug metabolism. Extensive studies have demonstrated a close association between DILI progression and ferroptosis, a process characterized by redox imbalance triggered by lipid peroxidation. As a key product of redox imbalance and a critical biomarker of DILI, peroxynitrite (ONOO-) plays a pivotal regulatory role in ferroptosis. To elucidate the precise mechanism of ONOO- in ferroptosis-mediated DILI, there is an urgent need for ONOO- fluorescent probes with high specificity, sensitivity and signal-to-noise ratio. This study innovatively modified the traditional pyridine hemicyanine fluorophore into a quinoline hemicyanine structure, achieving a red-shifted fluorescence emission wavelength through extended conjugation and enhanced electron delocalization. Systematic site screening identified diphenyl phosphate ester as the optimal reaction site, demonstrating exceptional specificity, sensitivity and 75 s response characteristics. By conjugating the optimized fluorophore with the reaction site via nucleophilic substitution, we successfully developed a novel ratiometric fluorescent probe, zt-4. Given the remarkable similarities in pathological mechanisms (including signaling pathways, regulatory nodes, and biomarkers) between osteoarthritis (OA) and DILI, we first validated the imaging performance of zt-4 in a complex inflammatory OA Model. Subsequently, we applied probe zt-4 to analyze ferroptosis-mediated DILI model at both cellular and murine levels. For the first time, our study revealed that the ferroptosis pathway dynamically regulates ONOO- levels in DILI, elucidating its molecular mechanism. These findings provide new theoretical foundations and intervention strategies for DILI treatment.
药物性肝损伤(DILI)是由药物代谢引起的肝毒性作用引起的。大量研究表明DILI进展与铁下垂密切相关,这一过程以脂质过氧化引发的氧化还原失衡为特征。作为氧化还原失衡的关键产物和DILI的重要生物标志物,过氧亚硝酸盐(ONOO-)在铁凋亡中起着关键的调节作用。为了阐明ONOO-在死铁介导的DILI中的确切机制,迫切需要具有高特异性、高灵敏度和高信噪比的ONOO-荧光探针。本研究创新性地将传统的吡啶半苯胺荧光团修饰为喹啉半苯胺结构,通过扩展共轭和增强电子离域实现了荧光发射波长的红移。系统的位点筛选确定磷酸二苯酯为最佳反应位点,表现出优异的特异性、敏感性和75 s的响应特性。通过亲核取代将优化的荧光团与反应位点偶联,我们成功地开发了一种新型的比例荧光探针zt-4。鉴于骨关节炎(OA)和DILI在病理机制(包括信号通路、调节节点和生物标志物)上的显著相似性,我们首先验证了zt-4在复杂炎性OA模型中的成像性能。随后,我们应用探针zt-4在细胞和小鼠水平上分析了铁中毒介导的DILI模型。本研究首次揭示了铁下垂途径动态调控DILI中ONOO-水平,阐明了其分子机制。这些发现为DILI的治疗提供了新的理论基础和干预策略。
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