Nano Today最新文献_第5页

Multifunctional dendrimer-peptide conjugates for MET receptor-specific imaging of cancer cells 用于癌细胞 MET 受体特异性成像的多功能树枝状聚合物-多肽共轭物

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-10-01 DOI: 10.1016/j.nantod.2024.102509

Jin Woong Lee , Kwangok P. Nickel , Rachel L. Minne , Justin J. Jeffery , Eduardo Aluicio-Sarduy , Carter Kim , DaWon Kim , Piper A. Rawding , Michael J. Poellmann , Narsimha Mamidi , Jonathan W. Engle , Jung Heon Lee , Hansoo Park , Reinier Hernandez , Randall J. Kimple , Andrew M. Baschnagel , Seungpyo Hong

The Mesenchymal Epithelial Transition (MET) receptor tyrosine kinase is frequently upregulated or mutated in various cancers. Targeting MET signaling pathway has been utilized as a treatment for cancer, since MET overexpression is often associated with poor prognosis. Selective imaging of MET-overexpressing tumor cells would thus provide a high diagnostic value; however, it remains elusive due to a lack of targeted imaging contrast agents. Herein, we have developed a multifunctional diagnostic dendrimer-peptide conjugate (DPC) system with a strong avidity to MET-expressing cancer cells. The system was prepared by conjugating MET-inhibiting peptides (C7) to generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers. Due to the dendrimer-mediated multivalent binding effect, the DPCs exhibited a significantly stronger binding to the human MET protein than free C7, as measured using surface plasmon resonance. Confocal microscopy revealed increased binding of the DPCs to the MET-expressing EBC-1 and UW-Lung-21 cells, whereas a MET knock-out cell line showed negligible interactions with the DPCs. The DPCs were then conjugated with Zirconium-89 for positron emission tomography and computed tomography (PET/CT) scanning, demonstrating their selective accumulation to MET-expressing tumors in vivo. Additionally, the plasma half-life of the DPCs was measured at ∼53 hours, which was significantly longer than free C7. These results collectively suggest that this DPC system has potential as a targeted imaging platform specific to MET-expressing tumors, which would be applicable to various cancer types.

间充质上皮转化（MET）受体酪氨酸激酶经常在各种癌症中上调或突变。靶向 MET 信号通路已被用作癌症的治疗手段，因为 MET 过表达通常与预后不良有关。因此，对 MET 过表达的肿瘤细胞进行选择性成像将具有很高的诊断价值；然而，由于缺乏有针对性的成像造影剂，这一目标仍难以实现。在此，我们开发了一种多功能诊断树枝状聚合物-肽共轭物（DPC）系统，该系统对表达 MET 的肿瘤细胞具有很强的亲和力。该系统是通过将 MET 抑制肽（C7）与第 7 代（G7）聚酰胺胺（PAMAM）树枝状聚合物共轭制备而成的。由于树枝状聚合物介导的多价结合效应，通过表面等离子共振测量，DPCs 与人类 MET 蛋白的结合力明显强于游离 C7。共聚焦显微镜显示，DPCs 与表达 MET 的 EBC-1 和 UW-Lung-21 细胞的结合力增强，而 MET 基因敲除细胞系与 DPCs 的相互作用微乎其微。然后将 DPCs 与锆-89 共轭，用于正电子发射断层扫描和计算机断层扫描（PET/CT），结果表明它们在体内可选择性地聚集到表达 MET 的肿瘤上。此外，DPCs 的血浆半衰期为 53 小时，明显长于游离 C7。这些结果共同表明，这种DPC系统有可能成为特异于MET表达肿瘤的靶向成像平台，适用于各种癌症类型。

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引用次数: 0

Complement opsonized protein corona activated by precoated immunoglobulin enables neutrophil-hitchhiking for rapid and enhanced drug delivery for acute liver failure recovery 由预包被免疫球蛋白激活的补体溶解蛋白电晕可使中性粒细胞搭便车，从而快速增强药物输送，促进急性肝功能衰竭的恢复

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-28 DOI: 10.1016/j.nantod.2024.102512

Keying Chen , Chunxiong Zheng , Yunjuan Lv , Pengkai Zhao , Tong Lin , Yanteng Xu , Huimin Kong , Ke Yi , Qingguo Zhong , Mingqiang Li , Yu Tao , Haixia Wang

In acute inflammation, the heightened activation and recruitment of immune cells present an opportunity to leverage them as natural carriers for efficient transport of diagnostic probes and nanotherapeutics. Although complement opsonization facilitates the internalization of nanomedicines by activated neutrophils, the development of strategies to specifically augment complement deposition remains a challenge. Herein, we engineer silymarin-loaded liposomes (Lips) coated with immunoglobulin G (IgG) to enhance complement 3 (C3) deposition in the protein corona, thereby enabling neutrophil-mediated, precise targeting to the site of inflammation. Through the examination of various serum proteins, we discover that IgG adsorption, particularly with its Fc portion exposed, prominently promotes C3 enrichment in the protein corona, resulting in C3 cleavage into iC3b. This facilitates the uptake of C3-enriched Lips by activated neutrophils with elevated C3 receptor expression, thus improving the efficiency and specificity of nanomedicine delivery to inflammatory site. Following the formation of neutrophil extracellular traps, the released nanomedicine effectively mitigates hepatocyte damage by eliminating accumulated reactive oxygen species and inducing a shift in macrophage polarization towards the anti-inflammatory M2 phenotype. Our IgG-modified nanomedicine demonstrates significant therapeutic efficacy against acute liver failure by regulating the protein corona and hitchhiking neutrophils, offering a promising strategy for efficient and precise treatment of inflammation.

在急性炎症中，免疫细胞的活化和招募加剧，为利用免疫细胞作为天然载体高效运输诊断探针和纳米治疗药物提供了机会。尽管补体疏松作用有利于活化的中性粒细胞内化纳米药物，但开发特异性增强补体沉积的策略仍是一项挑战。在这里，我们设计了涂有免疫球蛋白G（IgG）的水飞蓟素负载脂质体（Lips），以增强补体3（C3）在蛋白冠层中的沉积，从而实现由中性粒细胞介导的对炎症部位的精确靶向。通过对各种血清蛋白的研究，我们发现 IgG 的吸附，尤其是其 Fc 部分暴露在外时，可显著促进 C3 在蛋白电晕中的富集，从而使 C3 裂解成 iC3b。这有利于C3受体表达增高的活化中性粒细胞吸收富含C3的Lips，从而提高纳米药物输送到炎症部位的效率和特异性。在中性粒细胞形成细胞外陷阱后，释放的纳米药物通过消除累积的活性氧和诱导巨噬细胞向抗炎 M2 表型极化转变，有效减轻了肝细胞损伤。我们的IgG修饰纳米药物通过调节蛋白电晕和搭便车的中性粒细胞，对急性肝衰竭具有显著疗效，为高效、精确地治疗炎症提供了一种前景广阔的策略。

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引用次数: 0

Self-cascade ROS-trapping bioreaction system reverses stem cell oxidative stress fate for osteogenesis 自级联 ROS 捕获生物反应系统逆转干细胞氧化应激命运，促进骨生成

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-28 DOI: 10.1016/j.nantod.2024.102514

Jiawei Yang , Hao Gu , Yuhui Zhu , Jiaojiao Shao , Haishuang Chang , Mingliang Zhou , Jie Wang , Xinquan Jiang

Reactive oxygen species (ROS) scavenging is essential for periodontal regeneration. However, the dynamic change of the applied materials within the ROS-rich environment and the residual oxidation products in the host highly impact periodontal regeneration. This study successfully constructs a bioreaction system via thiol-ene click chemistry, leveraging the high affinity of glutathione (GSH) for ROS to attract excess ROS to the crosslinking points. Two minutes after hydrogen peroxide (H₂O₂) treatment, the ROS level in the G8–0 hydrogel acutely decreases, reaching a 4.4 % reduction within 10 minutes, confirming the ROS-trapping efficacy. Through a ‘bait switch-on’ mechanism, hexagonal boron nitride (hBN) takes over the captured ROS and the oxidation products of pectin further drive the reduction reaction, ultimately restoring the extracellular environment. The self-cascade products, oxidized hBN, reshape the intracellular oxidative stress (OS) environment, achieving a synergistic extra- and intra-cellular treatment. The significantly high reduced to oxidized glutathione (GSH/GSSG) ratio in G8–10 hydrogel (∼80 %) illustrates a reversal of oxidative stress in bone marrow stem cells (BMSCs). On a molecular level, the bioreaction system inhibits the NF-κB pathway, promoting the expression of key antioxidant genes (Nqo1 and Nrf2) and osteogenic molecules (ALP and OCN), thereby reversing the detrimental effects of OS on BMSCs. In vivo application demonstrated the system’s strong redox-balancing and osteogenic capabilities in the periodontal inflammation environment. This novel antioxidant bioreaction system, characterized by self-cascade ROS-trapping and product utilization, offers innovative treatment strategies for tissue regeneration under conditions of excessive OS.

清除活性氧（ROS）对牙周再生至关重要。然而，应用材料在富含 ROS 环境中的动态变化以及宿主体内残留的氧化产物对牙周再生有很大影响。本研究利用谷胱甘肽（GSH）对 ROS 的高亲和力将过量的 ROS 吸引到交联点，通过硫醇-烯点击化学成功构建了一个生物反应系统。过氧化氢（H2O2）处理两分钟后，G8-0 水凝胶中的 ROS 水平会急剧下降，在 10 分钟内降至 4.4%，从而证实了 ROS 的捕获功效。通过 "诱饵切换 "机制，六方氮化硼（hBN）接管了捕获的 ROS，果胶的氧化产物进一步推动了还原反应，最终恢复了细胞外环境。自级联产物--氧化的 hBN 重塑了细胞内的氧化应激（OS）环境，实现了细胞内外的协同处理。G8-10 水凝胶中还原型谷胱甘肽与氧化型谷胱甘肽（GSH/GSSG）的比率明显较高（80%），说明骨髓干细胞（BMSCs）中的氧化应激得到了逆转。在分子水平上，生物反应系统抑制了 NF-κB 通路，促进了关键抗氧化基因（Nqo1 和 Nrf2）和成骨分子（ALP 和 OCN）的表达，从而逆转了 OS 对骨髓干细胞的有害影响。体内应用证明了该系统在牙周炎症环境中强大的氧化还原平衡和成骨能力。这种新型抗氧化生物反应系统具有自级联捕获 ROS 和利用产物的特点，为 OS 过多条件下的组织再生提供了创新的治疗策略。

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引用次数: 0

DNA nanotube-carrying antimicrobial peptide confers improved anti-infective therapy 携带抗菌肽的 DNA 纳米管可提高抗感染治疗效果

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-27 DOI: 10.1016/j.nantod.2024.102508

Nier Wu , Shengnan Fu , Chenxi Dai , Lingfei Hu , Jiaxin Li , Fangzhou Chen , Lin Wang , Xin Su , Dongsheng Zhou

Antimicrobial peptides (AMPs) represent a good alternative for treating infections to overcome increasing antibiotic resistance problems. DNA nanostructures have been utilized as the delivery carrier of AMPs to enhance their performance, but mechanisms of action remain largely unclear. In this work, DNA nanotube (DNT) was chosen as a preferred carrier of AMPs owing to its high binding affinity and loading capacity, and an engineered broad-spectrum AMP named RP557 was screened as the cargo though molecular simulation and subsequent loading experiments. RP557 molecules were then loaded onto DNT through electrostatic interaction to construct RP557@DNT nanocomplex for improved anti-infective therapy. Loaded RP557 possessed the lower cytotoxicity to fibroblasts and epithelial cells and the higher compatibility to red blood cells relative to free RP557 in vitro, and RP557@DNT displayed the highly favored biodegradability and biosafety at the animal level. In addition, compared to free RP557, RP557@DNT endowed better bactericidal activity in vitro and in vivo because loaded RP557 exhibited higher resistance to serum protease degradation and controlled release onto bacterial cell membrane. The high therapeutic effect of RP557@DNT primarily depended on the acceleration of inflammation resolution (involving the reduction in proinflammatory factor production, innate immune cell recruitment, and adaptive immunity) and tissue repair (involving the up-regulation of multiple epidermal and dermal repair pathways). In summary, RP557@DNT showed significantly enhanced anti-enzymolysis, antibacterial activity, and biosafety relative to free RP557, and thus it represented a high-efficiency antibiotics-alternative strategy for treating refractory infections.

抗菌肽（AMPs）是治疗感染以克服日益严重的抗生素耐药性问题的良好替代品。DNA 纳米结构已被用作 AMPs 的传输载体，以提高其性能，但其作用机制仍不十分明确。在这项工作中，DNA 纳米管（DNT）因其高结合亲和力和负载能力而被选为 AMPs 的首选载体，并通过分子模拟和随后的负载实验筛选出一种名为 RP557 的工程化广谱 AMP 作为载体。然后通过静电作用将 RP557 分子负载到 DNT 上，构建 RP557@DNT 纳米复合物，用于提高抗感染治疗效果。与游离的 RP557 相比，负载的 RP557 在体外对成纤维细胞和上皮细胞的细胞毒性更低，与红细胞的相容性更高，而且 RP557@DNT 在动物实验中表现出良好的生物降解性和生物安全性。此外，与游离的 RP557 相比，RP557@DNT 在体外和体内都具有更好的杀菌活性，因为负载的 RP557 对血清蛋白酶降解具有更强的抵抗力，并可控地释放到细菌细胞膜上。RP557@DNT 的高治疗效果主要取决于炎症的加速消退（包括减少促炎因子的产生、先天性免疫细胞的招募和适应性免疫）和组织修复（包括上调多种表皮和真皮修复途径）。总之，与游离 RP557 相比，RP557@DNT 在抗酶溶解、抗菌活性和生物安全性方面都有显著提高，因此是治疗难治性感染的高效抗生素替代策略。

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引用次数: 0

Hydrogen nanobubbles enhancing antioxidant activity of glutathione peroxidase: Superiority at the nanoscale over molecular scale 氢纳米气泡增强谷胱甘肽过氧化物酶的抗氧化活性：纳米尺度优于分子尺度

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-26 DOI: 10.1016/j.nantod.2024.102510

You Zhang , Xiaofeng Wang , Shu Liu , Jing Wang , Pingping Zheng , Damin Xu , Qian Liu , Liming Wang , Wenhong Fan , Fengchang Wu

As novel antioxidants, hydrogen nanobubbles (NBs) intricately regulate the growth and developmental processes of organisms, bolstering their tolerance to external stresses. Despite their recognized potential, the precise antioxidative mechanisms remain inadequately elucidated. In this study, we present evidence supporting the protective role of hydrogen NBs in an oxidative stress system, utilizing Cu²⁺ as a prototypical inducer and Tetrahymena thermophila as a representative model organism. To elucidate the molecular mechanism of this phenomenon, we employed a comprehensive approach, integrating transcriptomic analysis and molecular dynamics simulations. Additionally, intrinsic differential scanning and surface plasmon resonance techniques were applied to unveil the molecular-level response and nanoscale interactions. Our investigation revealed that hydrogen NBs induce a notable upregulation in the expression of glutathione peroxidase (GPx). Moreover, compared to molecular hydrogen, hydrogen NBs have a more pronounced effect on the structural reconfiguration and catalytic efficacy of GPx, as demonstrated by the greater reduction in the distance between the catalytic center amino acids and a significant increase in GPx’s affinity for GSH. In summary, our findings underscore GPx as the targeted molecules through which hydrogen NBs exert their antioxidative effects. These insights contribute to a deeper comprehension of the molecular implications of hydrogen NBs and provide new perspectives for alleviating the toxicity of environmental pollutants.

作为一种新型抗氧化剂，纳米氢气泡（NBs）能错综复杂地调节生物体的生长和发育过程，增强其对外部压力的耐受力。尽管氢纳米气泡具有公认的潜力，但其确切的抗氧化机制仍未得到充分阐明。在本研究中，我们以 Cu2+ 为典型诱导剂，以嗜热四膜虫为代表性模式生物，提出了支持氢 NBs 在氧化应激系统中发挥保护作用的证据。为了阐明这一现象的分子机制，我们采用了一种综合方法，将转录组分析和分子动力学模拟结合起来。此外，我们还采用了本征差分扫描和表面等离子体共振技术来揭示分子级响应和纳米级相互作用。我们的研究发现，氢气 NB 可诱导谷胱甘肽过氧化物酶（GPx）的表达显著上调。此外，与分子氢相比，氢 NB 对 GPx 的结构重构和催化功效有更明显的影响，这表现在催化中心氨基酸之间的距离更小，GPx 对 GSH 的亲和力显著增加。总之，我们的研究结果表明，GPx 是氢核苷酸发挥抗氧化作用的目标分子。这些发现有助于加深对氢核糖分子意义的理解，并为减轻环境污染物的毒性提供了新的视角。

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引用次数: 0

Dynamics of catalyst nanoparticles quantified from in situ TEM video 从原位 TEM 视频中量化催化剂纳米颗粒的动态变化

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-24 DOI: 10.1016/j.nantod.2024.102505

Shuhui Liu , Qiao Zhao , Shaobo Han , Zhenghao Jia , Xiaoling Hong , Wei Liu

Quantification of the restructuring and migrating behaviors of working nanocatalysts at high spatiotemporal resolution is of a rigorous challenge but of vital significance to provide insights into the microstructural intrinsic of catalytic stability under the stimuli of the reaction environment. In this work, a deep learning-driven in situ TEM video quantification has been developed, capable of identifying and tracking every nanoparticle within the multi-particles video recorded during catalytic reaction. Through this methodology, evolutionary tracks of NiAu particles during catalyzing CO₂ hydrogenation and CuPd particles in a redox environment have been resolved. These quantitative behaviors of reconstruction and migration derived from in situ TEM data, for the first time, unravel the surface-anisotropic catalytic reaction over individual particle, which is consistently measured as multiple changing descriptors including particle diameter/area, circularity, and migration velocity. Such reaction and microstructure inhomogeneity deconstructed from working nanocatalyst offers convincing elucidation about the micro-dynamic mechanism of catalyst coalescence and migration. This paper highlights the merits of interdisciplinary study rooting in artificial intelligence-driven in situ TEM analysis.

以高时空分辨率量化工作中纳米催化剂的重组和迁移行为是一项艰巨的挑战，但对于深入了解反应环境刺激下催化稳定性的微观结构本质却具有重要意义。在这项工作中，开发了一种深度学习驱动的原位 TEM 视频量化方法，能够识别和跟踪催化反应过程中记录的多粒子视频中的每个纳米粒子。通过这种方法，我们解析了催化二氧化碳氢化过程中 NiAu 粒子和氧化还原环境中 CuPd 粒子的演化轨迹。这些从原位 TEM 数据中得出的重建和迁移的定量行为，首次揭示了单个颗粒表面各向异性的催化反应，并通过颗粒直径/面积、圆度和迁移速度等多个变化描述符进行了持续测量。从工作纳米催化剂中解构出的这种反应和微观结构不均匀性令人信服地阐明了催化剂凝聚和迁移的微观动力机制。本文强调了以人工智能驱动的原位 TEM 分析为基础的跨学科研究的优点。

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引用次数: 0

A chorismate mutase-targeted, core-shell nanoassembly-activated SERS immunoassay platform for rapid non-invasive detection of Acanthamoeba infection 用于快速无创检测棘阿米巴感染的络氨酸突变酶靶向核壳纳米组装激活型 SERS 免疫测定平台

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-21 DOI: 10.1016/j.nantod.2024.102506

Hyerin Lee , Min-Jeong Kim , Junkyu Chung , Wansun Kim , Hye-Jeong Jo , Tae Gi Kim , Jae-Ho Shin , Gi-Ja Lee , Fu-Shi Quan , Hyun-Hee Kong , Sang Woong Moon , Eun-Kyung Moon , Samjin Choi

Contact lens care and early diagnosis of Acanthamoeba keratitis (AK) are very important to prevent progression to blindness due to AK, which develops when Acanthamoeba attaches to contact lens-damaged corneas. Therefore, we propose a novel, non-invasive, immuno-surface-enhanced Raman scattering (SERS) sensing platform for rapid and accurate detection of Acanthamoeba infection in the tears and contact lens solutions of humans. This optic analysis method was based on the proven biological performance of chorismate mutase (CM)-specific monoclonal and polyclonal antibodies on trophozoite and cyst forms of Acanthamoeba castellanii, and its conditioned media. SERS-based, ultra-low concentration detection was achieved by the anisotropic fanblade-shaped core-shell nanoassembly (Ag@AuFNP) embedded with 4-fluorobenzenethiol Raman reporter. The immuno-SERS platform combining Ag@AuFNP and CM-specific antibody complexes was evaluated in vitro and in vivo. The non-invasive SERS-activated biosensing platform indicates strong feasibility for AK detection in human tears and contact lens solutions.

隐形眼镜护理和阿卡阿米巴角膜炎（AK）的早期诊断对于防止因阿卡阿米巴附着在隐形眼镜损坏的角膜上而导致失明非常重要。因此，我们提出了一种新型、非侵入式、免疫表面增强拉曼散射（SERS）传感平台，用于快速准确地检测人类泪液和隐形眼镜溶液中的棘阿米巴感染。这种光学分析方法基于络氨酸突变酶（CM）特异性单克隆和多克隆抗体在滋养体和囊肿型卡氏棘阿米巴及其条件培养基上已被证实的生物学性能。各向异性扇形核壳纳米组件（Ag@AuFNP）嵌入了 4-氟苯硫酚拉曼报告物，实现了基于 SERS 的超低浓度检测。结合 Ag@AuFNP 和 CM 特异性抗体复合物的免疫 SERS 平台在体外和体内进行了评估。非侵入式 SERS 激活生物传感平台表明，在人类眼泪和隐形眼镜溶液中检测 AK 具有很强的可行性。

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引用次数: 0

A cationic hydrogel with anti-IL-17A-specific nanobodies for rheumatoid arthritis treatment via inhibition of inflammatory activities of neutrophils 一种含有抗 IL-17A 特异性纳米抗体的阳离子水凝胶，可通过抑制中性粒细胞的炎症活动治疗类风湿性关节炎

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-20 DOI: 10.1016/j.nantod.2024.102507

Qiaoxuan Wang , Qi Cheng , Guangshuai Yao , Zhaolong Wang , Lingjiang Zhu , Zhiru Zeng , Lingyun Jia , Yan Du , Jing Xue , Changyou Gao

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease primarily driven by inappropriate infiltration and activation of immune cells and pro-inflammatory cytokines. Among them, neutrophils with high plasticity play a pathogenic role in RA by abnormal neutrophil immune activities. As anti-IL-17A therapies failed to achieve long-term ideal therapeutic outcomes in clinical trials, we speculated that the underlying cause may be associated with the abnormal activity of neutrophils that have a direct link to IL-17A. Herein, we created a cationic hydrogel loaded with anti-IL-17A nanobodies (Nbs) capable of synergistically weakening the inflammatory activities of neutrophils and relieving inflammation in RA. Based on the host-guest interaction, the hydrogel was comprised of β-cyclodextrin-modified hyperbranched polylysine (HBPL-CD) and adamantane-modified hyaluronic acid (HA-Ad). The physical properties were adjusted to match the mechanical environment of joints and enable injection. The hydrogel with Nbs could adsorb cell-free DNA (cfDNA) persistently and slowly release anti-IL-17A Nbs, which synergistically alleviated the inflammatory activities of neutrophils via inhibiting the IL-17A stimulated neutrophil extracellular traps (NETs) of neutrophils from RA patients and mice with collagen-induced arthritis (CIA), reducing the level of pro-inflammatory cytokines, and suppressing the inflammatory phenotype of neutrophils in vitro. The ankle injection of the hydrogel with Nbs into a mouse model of CIA could alleviate the RA symptoms in vivo. This novel platform is believed to provide a guideline for treating IL-17A-related diseases by combining Nbs with the immunoregulation of neutrophils.

类风湿性关节炎（RA）是一种慢性炎症性关节疾病，主要由免疫细胞和促炎细胞因子的不适当浸润和激活引起。其中，具有高度可塑性的中性粒细胞通过异常的中性粒细胞免疫活动在 RA 中发挥致病作用。由于抗IL-17A疗法在临床试验中未能达到长期理想的治疗效果，我们推测其根本原因可能与中性粒细胞的异常活动有关，而中性粒细胞的异常活动与IL-17A有直接联系。在此，我们创造了一种负载抗IL-17A纳米抗体（Nbs）的阳离子水凝胶，它能协同削弱中性粒细胞的炎症活性，缓解RA的炎症。根据主客体相互作用原理，水凝胶由β-环糊精修饰的超支化聚赖氨酸（HBPL-CD）和金刚烷修饰的透明质酸（HA-Ad）组成。对其物理性质进行了调整，使其与关节的机械环境相匹配，并能进行注射。含有Nbs的水凝胶能持久吸附无细胞DNA（cfDNA）并缓慢释放抗IL-17A Nbs，通过抑制RA患者和胶原诱导关节炎（CIA）小鼠中性粒细胞的IL-17A刺激的中性粒细胞胞外陷阱（NET），降低促炎细胞因子的水平，抑制体外中性粒细胞的炎症表型，从而协同缓解中性粒细胞的炎症活性。将含有 Nbs 的水凝胶通过脚踝注射到 CIA 小鼠模型中可减轻体内 RA 症状。通过将 Nbs 与中性粒细胞的免疫调节相结合，这一新型平台有望为治疗 IL-17A 相关疾病提供指导。

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引用次数: 0

Thermoelectric catalysis overcomes tumour “marginalization” of cytotoxic T-lymphocytes to boost immune checkpoint blockade therapy 热电催化克服肿瘤对细胞毒性 T 淋巴细胞的 "边缘化"，促进免疫检查点阻断疗法的发展

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-19 DOI: 10.1016/j.nantod.2024.102500

Chang Liu , Xuwu Zhang , Wenkang Tu , Kelong Fan , Xiyun Yan , Yuchu He , Dawei Gao

Although immune checkpoint blockade (ICB) therapy enhances the tumour recognition of cytotoxic T lymphocytes (CTLs), the limited infiltration of CTLs into the centre of solid tumours significantly restricts the effect of ICB therapy. Herein, we showed that increased tumour interstitial fluid pressure (TIFP) is a critical factor in the tumour “marginalization” of CTLs. Additionally, we utilized a spatiotemporally controllable thermoelectric catalytic nanodrug (BF@M) to decompose water from the tumour interstitial fluid into oxygen, effectively reducing the TIFP and leading to enhanced infiltration of CTLs from the periphery to the interior of the solid tumour. The results revealed that BF@M significantly increased the intratumor infiltration of CTLs in three different tumour-bearing mouse models, with a maximum increase of 18.1 times. Overall, this study highlighted the intrinsic relationship between TIFP and CTLs infiltration and the mechanism underlying the effect of the TIFP, successfully addressing the tumour “marginalization” of CTLs to enhance ICB therapy.

尽管免疫检查点阻断（ICB）疗法能增强细胞毒性T淋巴细胞（CTL）对肿瘤的识别能力，但CTL对实体瘤中心的有限浸润大大限制了ICB疗法的效果。在这里，我们发现肿瘤间质压力（TIFP）的增加是CTLs被肿瘤 "边缘化 "的关键因素。此外，我们利用一种时空可控的热电催化纳米药物（BF@M）将肿瘤间质中的水分解成氧气，从而有效降低肿瘤间质压力，增强 CTL 从实体瘤外围向内部的渗透。研究结果表明，在三种不同的肿瘤小鼠模型中，BF@M 能显著增加 CTLs 在肿瘤内的浸润，最大增幅达 18.1 倍。总之，该研究强调了TIFP与CTLs浸润之间的内在关系以及TIFP的作用机制，成功地解决了CTLs被肿瘤 "边缘化 "的问题，从而提高了ICB的治疗效果。

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引用次数: 0

Brillouin light scattering spectral fingerprinting of magnetic microstates in artificial spin ice 人工自旋冰中磁性微态的布里渊光散射光谱指纹图谱

IF 13.2 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2024-09-18 DOI: 10.1016/j.nantod.2024.102497

Amrit Kumar Mondal , Avinash Kumar Chaurasiya , Kilian D. Stenning , Alex Vanstone , Jack C. Gartside , Will R. Branford , Anjan Barman

The family of nanomagnetic arrays termed artificial spin ice (ASI) possess a vast range of metastable microstates. These states exhibit both exotic fundamental physics and more recently applied functionality, garnering attention as reconfigurable magnonic circuits and neuromorphic computing platforms. However, open questions remain on the role of microstate imperfections or angular disorder – particularly in the GHz response of the system. We report a study on the GHz dynamics of a series of five carefully prepared microstates in the same ASI sample, with both coexistence of vortex and uniformly magnetized macrospins, and disorder in the orientation of the macrospins at different vertices. We observe microstate-specific mode frequency shifting, mode creation and mode crossing. This versatility of characteristic spin-wave (SW) peaks for specific magnetic microstates in ASI enables identification of microstate configurations via SW spectral characterization. The wide reconfigurability of microstate-specific SW dynamics also opens avenues for developing rich magnonic devices operating in the GHz frequency regime and advances the understanding of ASI physics.

被称为人造自旋冰（ASI）的纳米磁阵列家族拥有多种可蜕变的微观状态。这些状态既展现了奇异的基础物理学，又具有最新的应用功能，作为可重新配置的磁性电路和神经形态计算平台而备受关注。然而，微态缺陷或角度无序的作用--尤其是在系统的 GHz 响应中的作用--仍然是一个未决问题。我们报告了在同一个 ASI 样品中精心制备的一系列五个微态的 GHz 动态研究，这些微态既有涡旋和均匀磁化大螺旋的共存，也有不同顶点大螺旋取向的无序。我们观察到微态特定的模式频率移动、模式创建和模式交叉。ASI 中特定磁性微态的特征自旋波（SW）峰的这种多功能性，使我们能够通过 SW 光谱特性鉴定微态配置。微态特异性 SW 动态的广泛可重构性还为开发在 GHz 频率机制下运行的丰富磁性器件开辟了途径，并推进了对人工晶体物理的理解。

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