Materials Today Bio最新文献_第4页

pH-responsive ZIF-8@quercetin nanoparticles induce pyroptosis for targeted gastric cancer therapy ph响应ZIF-8@quercetin纳米颗粒诱导胃癌靶向治疗焦亡

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-13 DOI: 10.1016/j.mtbio.2026.102806

Qian Xu , Xin Jin , Siyi Song , Hongyu Zhang , Huanxin Ding , Chuxuan Liu , Luyu Li , Shi Peng , Yugang Cheng , Mingwei Zhong , Linchuan Li , Jiankang Zhu , Shuohui Dong , Guangyong Zhang

Gastric cancer (GC) remains a major global health burden, with limited effective therapies and poor prognosis. Quercetin (Que), a natural flavonoid, exhibits anticancer activity but suffers from poor water solubility, limited oral bioavailability, and rapid metabolic clearance, which severely restrict its clinical translation. These pharmacokinetic limitations necessitate an efficient delivery system capable of stabilizing Que in circulation and enabling tumor-specific release. To address these limitations, a zeolitic imidazolate framework-8 (ZIF-8) was developed based on nanoparticles that encapsulate Que (ZIF-8@Que), enabling high loading efficiency and pH-responsive release. ZIF-8@Que was efficiently internalized by GC cells and localized within lysosomes, where the acidic environment accelerated drug release. This process coincided with marked reactive oxygen species (ROS) generation, leading to mitochondrial membrane depolarization, ATP depletion, and ultrastructural damage. Cellular analyses further revealed features consistent with pyroptotic cell death, including lactate dehydrogenase (LDH) release, increased staining for cleaved caspase-1 and cleaved gasdermin-D (GSDMD), and enhanced TUNEL-positive signals. Compared with free Que or empty ZIF-8, ZIF-8@Que demonstrated stronger inhibition of proliferation, migration, and invasion in vitro, while in vivo studies confirmed preferential tumor accumulation, robust tumor suppression, and minimal systemic toxicity. Collectively, these findings highlight ZIF-8@Que as a safe and effective nanoparticle that integrates drug delivery with ROS-mediated pyroptosis, offering a promising strategy to overcome the limitations of Que monotherapy and advance GC therapy.

胃癌（GC）仍然是全球主要的健康负担，有效治疗方法有限，预后不良。槲皮素（Quercetin, Que）是一种天然类黄酮，具有抗癌活性，但水溶性差，口服生物利用度有限，代谢清除快，严重限制了其临床转化。这些药代动力学限制需要一种有效的递送系统，能够稳定Que在循环中并使肿瘤特异性释放。为了解决这些限制，基于封装Que （ZIF-8@Que）的纳米颗粒开发了沸石咪唑盐框架-8 (ZIF-8)，实现了高负载效率和ph响应释放。ZIF-8@Que被GC细胞有效地内化并定位于溶酶体中，酸性环境加速了药物释放。这一过程与显著的活性氧（ROS）产生同时发生，导致线粒体膜去极化、ATP耗竭和超微结构损伤。细胞分析进一步揭示了与热腐细胞死亡相一致的特征，包括乳酸脱氢酶（LDH）释放，裂解caspase-1和裂解gasdermind （GSDMD）染色增加，tunel阳性信号增强。与游离的Que或空的ZIF-8相比，ZIF-8@Que在体外表现出更强的增殖、迁移和侵袭抑制作用，而体内研究证实了肿瘤的优先积累、强大的肿瘤抑制作用和最小的全身毒性。总的来说，这些发现强调ZIF-8@Que是一种安全有效的纳米颗粒，可以将药物传递与ros介导的焦死结合起来，为克服Que单药治疗的局限性和推进GC治疗提供了一种有希望的策略。

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引用次数: 0

Hierarchical silver-tannic acid hydrophobic coating via layer-by-layer assembly for antibiofilm applications on urinary catheters 通过逐层组装的分级银单宁酸疏水涂层用于导尿管的抗菌膜应用

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-08 DOI: 10.1016/j.mtbio.2026.102775

Sivakumar Bose , Myungji Kang , Seonho Jung , Mijeong Kim , Chanwoo Yoon , Priya Ranganathan , Seung Yun Nam , Hyun Wook Kang

Catheter-associated urinary tract infections (CAUTIs) are a serious global concern due to the emergence of drug-resistant bacteria and the biofilm formation on urinary catheters (UCs). Surface modification strategies have been identified as a prominent and cost-effective method to address this issue owing to its tunable properties, which effectively combat the biofilm formation on UCs. This study reports the development of a hydrophobic-silver nanoparticles (Ag NPs) decorated tannic acid-based coating on silicone UC using a layer-by-layer (LBL) approach that can effectively eradicate Escherichia coli (E. coli) biofilms. The LBL coating (PFDT-Ag-Dex) consists of a tannic acid (TA)-(3-aminoprophyl) triethoxysilane (APTES) NPs deposition, followed by Ag NPs decoration and 1H,1H,2H,2H-perfluorodecane-thiol (PFDT) layers, which impart the hydrophobicity, biocompatibility, antibacterial activity, and coating adhesion, respectively. Formation of the LBL coating on the Si catheter was successfully confirmed through extensive characterizations. In vitro and in vivo investigations showed that the PFDT-Ag-Dex coated Si catheter significantly inhibited the E. coli biofilm formation with ∼95 % efficiency due to the combined effects of the hydrophobic properties, tannic acid and Ag⁺ ions causing the cell membrane disruption. Furthermore, in vivo studies using mouse and rabbit animal models confirmed the biosafety of the PFDT-Ag-Dex-coated Si catheter, which exhibited a negligible inflammatory response. The studies suggest that the Ag-TA-hydrophobic coated catheter is a promising solution for combating the urinary tract infections.

导尿管相关性尿路感染（CAUTIs）由于耐药细菌的出现和导尿管生物膜的形成而成为全球关注的一个严重问题。由于其可调节的特性，表面改性策略已被确定为解决这一问题的一种突出且具有成本效益的方法，可以有效地对抗UCs上的生物膜形成。本研究报道了一种疏水银纳米颗粒（Ag NPs）修饰的单宁酸基涂层，该涂层采用逐层（LBL）方法，可以有效地根除大肠杆菌（E. coli）生物膜。LBL涂层（PFDT-Ag- dex）由单宁酸(TA)-（3-氨基酚）三乙氧基硅烷（APTES） NPs沉积，Ag NPs装饰和1H，1H,2H，2H-全氟癸烷-硫醇（PFDT）层组成，分别具有疏水性，生物相容性，抗菌性和涂层粘附性。通过广泛的表征，成功地证实了硅导管上LBL涂层的形成。体外和体内研究表明，PFDT-Ag-Dex包覆的Si导管由于其疏水性、单宁酸和银+离子的共同作用导致了细胞膜的破坏，显著抑制了大肠杆菌生物膜的形成，效率为95%。此外，使用小鼠和兔子动物模型进行的体内研究证实了pfdt - ag - dex涂层Si导管的生物安全性，其炎症反应可以忽略。这些研究表明ag - ta疏水涂层导尿管是对抗尿路感染的一种很有前途的解决方案。

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引用次数: 0

Antithrombotic and antibacterial surface coating based on spiky silver nanoparticles: A counterattack against clotting and biofilm 基于针状银纳米粒子的抗血栓和抗菌表面涂层：对凝血和生物膜的反击

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-06 DOI: 10.1016/j.mtbio.2026.102762

Cuong Hung Luu , Shehzahdi S. Moonshi , Akriti Nepal , Binura Perera , Dimple Sajin , Haotian Cha , Dieu Ngoc Nguyen , Nam-Trung Nguyen , Hang Thu Ta

Blood-contacting medical devices such as vascular grafts, stents, and catheters are indispensable in life-saving interventions but remain prone to thrombosis and bacterial infection. These complications are often synergistic, with clot formation facilitating bacterial colonisation and biofilm growth, yet most surface coatings lack active countermeasures once thrombi or biofilms have developed. In this study, we hypothesised that integrating spiky silver-coated iron oxide nanoparticles (AgIONPs) with poly(ethylene glycol) (PEG) into a surface coating could provide both passive and active protection. AgIONPs offer strong photothermal properties under 808 nm laser irradiation for on-demand thrombolysis and biofilm disruption, while PEG contributes antifouling, anticoagulant, and biocompatible characteristics. The optimised AgIONPs–PEG coating exhibited safe photothermal heating (<45 °C), effectively lysed thrombi in static and dynamic models, and disrupted most biofilm biomass after a single irradiation cycle. Antithrombogenicity assays confirmed PEG's ability to reduce biofouling and improve haemocompatibility. Biocompatibility was further validated through in vitro, in ovo, and in vivo assays, with reduced immune-mediated inflammation. These findings highlight a multifunctional, responsive coating that could extend the lifespan and reliability of blood-contacting devices, offering a promising platform for next-generation photothermal materials in biomedical applications.

与血液接触的医疗设备，如血管移植物、支架和导管，在挽救生命的干预措施中是必不可少的，但仍然容易形成血栓和细菌感染。这些并发症通常是协同作用的，凝块的形成促进了细菌定植和生物膜的生长，然而，一旦血栓或生物膜形成，大多数表面涂层缺乏有效的对策。在这项研究中，我们假设将尖刺的镀银氧化铁纳米颗粒（AgIONPs）与聚乙二醇（PEG）结合到表面涂层中可以提供被动和主动保护。AgIONPs在808 nm激光照射下具有强大的光热特性，可用于按需溶栓和生物膜破坏，而PEG具有防污、抗凝和生物相容性特性。优化后的AgIONPs-PEG涂层具有安全的光热加热（<45°C），在静态和动态模型中有效地溶解血栓，并且在单次照射循环后破坏大多数生物膜生物量。抗血栓性试验证实了聚乙二醇减少生物污垢和改善血液相容性的能力。通过体外、蛋内和体内实验进一步验证了生物相容性，并减少了免疫介导的炎症。这些发现强调了一种多功能、反应灵敏的涂层，可以延长血液接触装置的寿命和可靠性，为下一代生物医学应用中的光热材料提供了一个有前途的平台。

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引用次数: 0

Natural polysaccharide-nucleic acid nanocomplex alleviates myocardial infarction by driving chronologically programmed macrophage polarization 天然多糖核酸纳米复合物通过驱动按时间顺序编程的巨噬细胞极化减轻心肌梗死

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 10.1016/j.mtbio.2026.102831

Xiang Guo , Shaodong Zhai , Hongnv Zhang , Zhenghao Wang , Nan Hu , Ruiping Zhang

In the temporal pathological progression of myocardial infarction (MI), acute ischemic injury triggers a macrophage-dominated inflammatory response, where the early M1 phenotype polarization aids in necrotic tissue clearance. However, persistent inflammation drives a pro-fibrotic shift, leading to cardiac remodeling and heart failure, rendering single-target therapies largely ineffective in addressing the full pathological course. To address this challenge, we developed a temporally modulated nanodelivery system. This platform integrates the natural immunomodulator zymosan A (ZymA) with siRNA-21 (SiR21) through intelligent assembly, enabling dual immunoregulatory and gene-silencing functions (ZymA@SiR21). Formulation optimization of ZymA enhanced particle uniformity and surface charge density, improving electrostatic binding with the cationic polymer PDMA for efficient SiR21 loading while boosting biosafety and immune tolerance. The system is associated with the binding of mannose groups on the ZymA surface to mannose receptors to achieve macrophage-specific targeting. This nanoplatform demonstrates time-dependent therapeutic precision: (1) During acute MI, ZymA induces macrophage polarization toward the M1 phenotype, enhancing phagocytic clearance of necrotic debris; (2) In the chronic-phase, released SiR21 sustains macrophage reprogramming to reparative M2 phenotypes and inhibits fibroblast hyperactivation. This “clearance-to-repair” strategy achieved superior outcomes in animal models and no systemic immune hyperactivation. By orchestrating macrophage dynamics, the system accelerates the restoration of inflammation-repair balance post-MI, offering a paradigm-shifting approach for stage-specific cardiac therapy.

在心肌梗死（MI）的时间病理进展中，急性缺血性损伤触发巨噬细胞主导的炎症反应，其中早期M1表型极化有助于坏死组织清除。然而，持续的炎症驱动促纤维化转变，导致心脏重塑和心力衰竭，使得单靶点治疗在解决整个病理过程中基本上无效。为了解决这一挑战，我们开发了一种暂时调制的纳米递送系统。该平台通过智能组装整合天然免疫调节剂ZymA （ZymA）和siRNA-21 (SiR21)，实现免疫调节和基因沉默双重功能（ZymA@SiR21）。优化了ZymA的配方，增强了颗粒均匀性和表面电荷密度，改善了与阳离子聚合物PDMA的静电结合，从而有效地装载SiR21，同时提高了生物安全性和免疫耐受性。该系统与ZymA表面的甘露糖基团与甘露糖受体的结合有关，以实现巨噬细胞特异性靶向。该纳米平台具有时间依赖性治疗精度：(1)急性心肌梗死期间，ZymA诱导巨噬细胞向M1表型极化，增强坏死碎片的吞噬清除；(2)在慢性期，释放的SiR21维持巨噬细胞重编程至修复性M2表型，并抑制成纤维细胞过度活化。这种“清除-修复”策略在动物模型中取得了优异的结果，没有出现全身免疫过度激活。通过协调巨噬细胞动力学，该系统加速心肌梗死后炎症修复平衡的恢复，为特定阶段的心脏治疗提供了一种范式转换方法。

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引用次数: 0

HOCl and viscosity dual-responsive fluorescent probe for accurate discrimination between early hepatocellular carcinoma and acute liver injury HOCl和黏度双响应荧光探针对早期肝癌和急性肝损伤的准确鉴别

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.mtbio.2026.102816

Jiakang Sun , Lidong Cao , Mengmeng Dong , Yumeng Liu , Yun Wang , Yong Zhan

The accurate differentiation between early-stage hepatocellular carcinoma (HCC) and acute liver injury (ALI) remains a critical yet unresolved challenge in clinical practice, as these conditions share overlapping symptoms and biomarkers, often leading to misdiagnosis with conventional techniques. Although fluorescent probes offer potential for high-sensitivity imaging, existing designs typically detect only a single parameter and lack subcellular targeting precision. Consequently, a methodology that simultaneously visualizes multiple pathology-specific biomarkers within a key organelle for precise discrimination is urgently needed. Here, we present a lipid droplet-targeted, dual-channel fluorescent probe, TPA-DCN-TPE, which independently monitors microenvironmental viscosity and hypochlorous acid (HOCl). This probe exhibits a remarkable 1532-fold fluorescence enhancement in response to viscosity (red channel) and a 363-fold turn-on response to HOCl (green channel). Crucially, we discovered a distinct red-to-green signal ratio that clearly discriminates HCC (high ratio) from ALI (low ratio) in vivo, ex vivo, and in tissue sections. Our work establishes a quantifiable optical criterion for differentiating these liver pathologies, thereby addressing a major diagnostic gap. We anticipate this dual-parameter imaging strategy will advance the precision diagnosis of liver diseases and provide a versatile platform for studying organelle-specific microenvironments in other metabolic and inflammatory disorders.

早期肝细胞癌（HCC）和急性肝损伤（ALI）的准确区分在临床实践中仍然是一个关键但尚未解决的挑战，因为这些疾病具有重叠的症状和生物标志物，经常导致传统技术的误诊。虽然荧光探针提供了高灵敏度成像的潜力，但现有的设计通常只检测单个参数，缺乏亚细胞靶向精度。因此，迫切需要一种在关键细胞器内同时可视化多个病理特异性生物标志物以进行精确区分的方法。在这里，我们提出了一种针对脂滴的双通道荧光探针，TPA-DCN-TPE，它可以独立监测微环境粘度和次氯酸（HOCl）。该探针对粘度（红色通道）的荧光响应增强了1532倍，对HOCl（绿色通道）的荧光响应增强了363倍。至关重要的是，我们发现了一个明显的红绿信号比，可以在体内、离体和组织切片中清楚地区分HCC（高比率）和ALI（低比率）。我们的工作建立了一个可量化的光学标准来区分这些肝脏病理，从而解决了一个主要的诊断差距。我们预计这种双参数成像策略将促进肝脏疾病的精确诊断，并为研究其他代谢和炎症疾病的细胞器特异性微环境提供一个通用平台。

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引用次数: 0

Targeting multidrug-resistant Candida: CuxTe nanoflowers synergistically facilitate fungal clearance via cuproptosis death and host immune activation 靶向多重耐药念珠菌：CuxTe纳米花通过铜胞菌死亡和宿主免疫激活协同促进真菌清除

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.mtbio.2026.102857

Yong he , Jianguo Niu , Wenqiang Huang , Changshan Ju , Shengqun Deng , Juanjuan Cui , Xianwen Wang , Mao Zhang

Candida species are common infectious pathogens that can cause invasive infections with potentially life-threatening consequences. Current treatments for invasive Candida infections are primarily azoles and echinocandins. However, emerging antifungal drug resistance compromises therapeutic efficacy. Herein, a stable Cu_xTe nanoflower was designed to combat fungal infections via cuproptosis death and immune activation. Firstly, Cu and Te precursors were added to an auxiliary reducing agent and solvent, and Cu_xTe nanoflowers with a multibranched dendritic structure were synthesized via a temperature-controlled solution-phase method. Cu_xTe nanoflowers effectively inhibit fungal growth, damage fungal cell membranes and walls, and show significant fungicidal activity even against the multidrug-resistant fungus Candida auris. Furthermore, they significantly disrupt fungal biofilms and inhibit their growth and maturation. Cu²⁺ ions released in the weakly acidic fungal microenvironment penetrate fungal cells, inducing copper overload. Transcriptional and cytological analyses revealed that Cu_xTe treatment disrupted the mitochondrial membrane potential, altered membrane permeability, triggered insoluble Dlat protein aggregation, blocked the TCA cycle, impaired mitochondrial function, and ultimately induced fungal cuproptosis death. Simultaneously, they promote proinflammatory macrophage polarization, exerting synergistic antifungal effects. In summary, this therapeutic strategy integrates synergistic dual-pathway mechanisms: fungal cuproptosis death and immune activation, providing a new approach for treating antifungal infections.

念珠菌是常见的感染性病原体，可引起侵袭性感染，并可能造成危及生命的后果。目前治疗侵袭性念珠菌感染的主要方法是唑类药物和棘珠菌素。然而，新出现的抗真菌药物耐药性影响了治疗效果。本文设计了一种稳定的CuxTe纳米花，通过cupropsis死亡和免疫激活来对抗真菌感染。首先，将Cu和Te前驱体加入到辅助还原剂和溶剂中，通过温控液相法合成了具有多支枝晶结构的CuxTe纳米花。CuxTe纳米花能有效抑制真菌生长，破坏真菌细胞膜和细胞壁，甚至对多重耐药真菌念珠菌也表现出显著的杀真菌活性。此外，它们显著破坏真菌生物膜，抑制其生长和成熟。弱酸性真菌微环境中释放的Cu2+离子穿透真菌细胞，诱导铜超载。转录和细胞学分析显示，CuxTe处理破坏了线粒体膜电位，改变了膜通透性，引发了不溶性的Dlat蛋白聚集，阻断了TCA循环，损害了线粒体功能，最终诱导真菌铜原性死亡。同时，它们促进促炎巨噬细胞极化，发挥协同抗真菌作用。总之，这种治疗策略整合了协同双途径机制：真菌铜变形死亡和免疫激活，为治疗抗真菌感染提供了一种新的途径。

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引用次数: 0

Living bacterial reactor potently activates tumor immunogenic ferroptosis via cysteine depletion and photothermal therapy 活菌反应器通过半胱氨酸耗散和光热疗法有效激活肿瘤免疫原性铁下垂

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-02-01 DOI: 10.1016/j.mtbio.2026.102843

Mengen Guo , Wenjie Xu , Yanjin Peng , Yucheng Tang , Xinyan Hao , Tiantian Tang , Xinying Liu , Hai Huang , Ruyue Han , Junyong Wu , Daxiong Xiang

Bacterial combination therapy offers immense promise for treating aggressive "cold" solid tumors, such as triple-negative breast cancer (TNBC). However, the clinical translatability of traditional genetic engineering is often hampered by operational complexity and genetic instability. Here, we developed A-SPB—a non-genetically engineered, multi-functional living bioreactor based on Shewanella oneidensis MR-1 (SO), surface-modified with Prussian blue (PB) nanoparticles and attenuated via deoxycholic acid (DA) treatment. This platform serves as an in situ metabolic factory that "hijacks" the sulfur-metabolism within the hypoxic tumor microenvironment. By actively depleting cysteine, A-SPB not only starves the glutathione (GSH) synthesis pathway but also generates hydrogen sulfide (H₂S) to inhibit the transsulfuration bypass, leading to a dual-pronged collapse of the GSH/GPX4 antioxidant axis and triggering robust tumor ferroptosis. This metabolic sensitization is further amplified by the PB-mediated photothermal therapy (PTT), which generates localized hyperthermia and excessive reactive oxygen species (ROS). Notably, the PTT serves as a dual-functional "bio-switch": it promotes acute tumor ablation while simultaneously triggering bacterial self-lysis to ensure biosafety. This programmed lysis releases a synergistic cocktail of bacterial PAMPs and tumor-derived DAMPs, which effectively remodels the immunosuppressive TME and initiates a potent systemic antitumor immune response. By integrating metabolic reprogramming, sensitized ferroptosis, and on-demand immune activation through simple surface engineering, this study provides a highly translatable and safe paradigm for the next generation of living bacterial therapeutics.

细菌联合疗法为治疗侵袭性“冷”实体肿瘤（如三阴性乳腺癌（TNBC））提供了巨大的希望。然而，传统基因工程的临床可译性往往受到操作复杂性和遗传不稳定性的阻碍。在这里，我们开发了a - spb -一种基于希瓦氏菌mr1 （SO）的非基因工程多功能活生物反应器，表面用普鲁士蓝（PB）纳米颗粒修饰，并通过脱氧胆酸（DA）处理减毒。这个平台作为一个原位代谢工厂，在缺氧的肿瘤微环境中“劫持”硫代谢。通过主动消耗半胱氨酸，a - spb不仅饥饿谷胱甘肽（GSH）合成途径，还产生硫化氢（H2S）抑制转硫旁路，导致GSH/GPX4抗氧化轴双管崩溃，引发恶性肿瘤铁凋亡。pb介导的光热疗法（PTT）会产生局部高温和过多的活性氧（ROS），从而进一步放大这种代谢敏化。值得注意的是，PTT作为一种双重功能的“生物开关”：它促进急性肿瘤消融，同时触发细菌自裂解以确保生物安全。这种程序化的裂解释放细菌PAMPs和肿瘤来源的DAMPs的协同鸡尾酒，有效地重塑免疫抑制的TME，并启动有效的全身抗肿瘤免疫反应。通过简单的表面工程整合代谢重编程、致敏性铁死亡和按需免疫激活，该研究为下一代活细菌治疗提供了高度可翻译和安全的范例。

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引用次数: 0

Intelligent nanoliposome ameliorate chronic intermittent hypoxia-mediated neuronal injury via a dual regulation microglial inflammation strategy 智能纳米脂质体通过双调节小胶质细胞炎症策略改善慢性间歇性缺氧介导的神经元损伤

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-02-04 DOI: 10.1016/j.mtbio.2026.102865

Hongwei Wang , Xu Wang , Yun Zhu , Zhiyuan Niu , Xiwen Ou , Weiyu Zhang , Shuting Zhuang , Yun Ke , Fan Yang , Mingliang Pei , Song Liu

The etiology of obstructive sleep apnea syndrome (OSAS)-associated cognitive dysfunction is unclear and complex. There is growing evidence demonstrate that hyper-activated neuroinflammation, M1 phenotypic microglia polarization, and subsequent neuronal inflammatory damage induced by chronic intermittent hypoxia (CIH) pose a crucial role in OSAS-related cognitive dysfunction. However, the regulatory mechanisms remain unclear, and during treatment, there are inevitable issues with small molecule drugs such as hydrophobicity, lack of targeting, and uncontrolled dosages, especially their inability to cross the blood-brain barrier (BBB), which severely hinders the treatment of CIH related cognitive dysfunction. Herein, a “dual regulation” microglial inflammation strategy was proposed using intelligent nanoliposomes (Ang-Lip@BAY/GW1929), capable of simultaneously regulating PPARγ signaling and IκBα/p65 pathway to reverse the inflammatory microglia transformation. The cationic Ang-Lip@BAY/GW1929 was innovatively used for the dual-targeted identification of CIH-activated microglia that highly express LRP-1 and carry a negative surface charge, to achieve efficient delivery and release of drugs. Simultaneously, PPARγ agonist (GW1929), and IκBα phosphorylation inhibitor (BAY) were delivered from ROS-responsive Ang-Lip@BAY/GW1929 to coordinate the inhibition of NF-κB pathway through PPARγ and IκBα/p65 signaling to systemically regulate microglial polarization, neuroinflammation, neuronal damage, and cognitive dysfunction. Collectively, the study proposed strategies for building bio-targeted liposome-based nanovector to relieve CIH-induced neuron injury, and systematically described treatment mechanisms on CIH related impairment, opening a new path for the treatment of CIH related cognitive dysfunction.

阻塞性睡眠呼吸暂停综合征（OSAS）相关认知功能障碍的病因尚不清楚且复杂。越来越多的证据表明，慢性间歇性缺氧（CIH）引起的神经炎症过度激活、M1型小胶质细胞极化以及随后的神经元炎症损伤在osas相关认知功能障碍中起着至关重要的作用。然而，其调控机制尚不清楚，在治疗过程中，小分子药物不可避免地存在疏水性、缺乏靶向性、剂量不受控制等问题，尤其是不能穿过血脑屏障（BBB），严重阻碍了CIH相关认知功能障碍的治疗。本文提出了一种“双调控”小胶质细胞炎症策略，使用智能纳米脂质体（Ang-Lip@BAY/GW1929），能够同时调节PPARγ信号和i - κ b α/p65途径，逆转炎症性小胶质细胞转化。创新地利用阳离子Ang-Lip@BAY/GW1929对高表达LRP-1、表面带负电荷的cih激活小胶质细胞进行双靶向鉴定，实现药物的高效递送和释放。同时，PPARγ激动剂（GW1929）和i -κB α磷酸化抑制剂（BAY）通过ros应答Ang-Lip@BAY/GW1929传递，通过PPARγ和i -κB α/p65信号协调NF-κB通路的抑制，系统调节小胶质细胞极化、神经炎症、神经元损伤和认知功能障碍。综上所述，本研究提出了构建生物靶向脂质体纳米载体减轻CIH诱导的神经元损伤的策略，并系统描述了CIH相关损伤的治疗机制，为CIH相关认知功能障碍的治疗开辟了新的途径。

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引用次数: 0

Hollow nanofactory with dotted interior surface produces potent hydroxyl radical to combat drug-resistant large tumors 内表面呈点状的空心纳米工厂可产生有效的羟基自由基，以对抗耐药的大肿瘤

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 10.1016/j.mtbio.2026.102859

Jing Yang , Tianshui Bai , Haobin Cai , Haolong Ma , Bin Ren , Zongheng Li , Qingdeng Fan , Lin Huang , Gang Liu , Guobin Hong , Zheyu Shen

Ferroptosis, a novel form of programmed cell death, is highly dependent on intracellular hydrogen peroxide (H₂O₂) and Fe²⁺ levels. Numerous nanomaterials have been developed to co-deliver H₂O₂ and Fe²⁺ or their prodrugs into tumor cells, aiming to enhance hydroxyl radical (•OH) level via Fenton reaction. However, the •OH generation efficacy is frequently undermined by catalase (CAT) and ferritin in cytoplasm, which can respectively catalyze H₂O₂ to H₂O and oxidize Fe²⁺ to Fe³⁺. Herein, we designed and constructed a hollow nanofactory with dotted interior surface (HNDIS), which is composed of hollow mesoporous iron oxide nanoparticle (HMION, “house” of the nanofactory) with mesoporous channels (“window” of the nanofactory), and ultrasmall gold nanoparticles (AuNP) on the interior surface (“machine” of the nanofactory). The unique “window” allows pass for glucose to co-work with AuNP and HMION to drive H₂O₂ production and Fe²⁺ release, and then generate a huge amount of •OH. Macromolecules cannot pass through the “window”, which prevents the undesirable catalysis of ferritin and CAT. In vitro and in vivo experiments have demonstrated potent •OH production ability and powerful tumor suppression efficacy based on ferroptosis for HNDIS, offering a promising pathway to combat drug-resistant large tumors.

铁死亡是一种新的程序性细胞死亡形式，高度依赖于细胞内过氧化氢（H2O2）和Fe2+水平。许多纳米材料已经被开发出来，用于将H2O2和Fe2+或其前药共同递送到肿瘤细胞中，旨在通过Fenton反应提高羟基自由基（•OH）水平。然而，细胞质中过氧化氢酶（CAT）和铁蛋白（ferritin）的作用经常破坏•OH的生成效率，这两种酶分别催化H2O2生成H2O和将Fe2+氧化为Fe3+。在此，我们设计并构建了一个中空点状内表面纳米工厂（HNDIS），它由中空的介孔氧化铁纳米粒子（HMION，纳米工厂的“房子”）和具有介孔通道（纳米工厂的“窗口”）的中空介孔氧化铁纳米粒子（HMION，纳米工厂的“窗口”）和内表面的超细金纳米粒子（AuNP）组成（纳米工厂的“机器”）。独特的“窗口”允许葡萄糖与AuNP和HMION共同作用，驱动H2O2的产生和Fe2+的释放，然后产生大量的•OH。大分子不能通过“窗口”，这阻止了铁蛋白和CAT的不良催化作用。体外和体内实验表明，基于铁下垂的HNDIS具有强大的•OH生成能力和强大的肿瘤抑制作用，为对抗耐药大肿瘤提供了一条有希望的途径。

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引用次数: 0

Feasibility of combining JAK1 gene editing via CRISPR-CasRx with EGCG–lactoferrin nanoparticle therapy in a microneedle-based platform for atopic dermatitis CRISPR-CasRx结合JAK1基因编辑与egcg -乳铁蛋白纳米颗粒治疗特应性皮炎微针平台的可行性

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.mtbio.2026.102884

Huanqing Zhu , Haonan Yu , Mengxin Huang, Panjie Sun, Yuanfang Tang, Zhanyi Zhang, Puming He, Youying Tu, Bo Li

Atopic dermatitis (AD) is an inflammatory skin disease characterized by a complex pathogenesis. Current clinical treatments exhibit several limitations, including low efficacy and considerable side effects, prompting a growing interest in novel therapeutic strategies. In this study, we developed a microneedle-assisted dual-nano drug delivery strategy that targets both oxidative stress and Janus kinase 1 (JAK1) expression, aiming for enhanced therapy of AD. Self-assembling nanoparticles (NPs) incorporating epigallocatechin gallate (EGCG) and lactoferrin were developed to effectively modulate oxidative stress. Concurrently, CRISPR-CasRx technology was employed to silence JAK1, and nanoparticles were constructed by encapsulating CasRx and siRNA within poly (β-amino ester) (PBAE). Both types of NPs were successfully delivered to skin lesions in AD mice through microneedles, either individually or combined, resulting in significant alleviation of symptoms. Treatment reduced dermatitis severity scores and splenomegaly, decreased epidermal thickness and mast cell infiltration, and increased collagen fiber content. Additionally, levels of inflammatory cytokines (IL-1β, IL-4, IL-13) and oxidative DNA damage marker (8-OHdG) in dorsal skin tissues were lowered, accompanied by decreased serum levels of thymic stromal lymphopoietin (TSLP) and IgE. The therapy also suppressed JAK1 expression and activated the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase 1‌ (HO-1) antioxidant pathway, except for PBAE-plasmid NP-loaded microneedles, which did not significantly increase HO-1 expression. Notably, microneedles containing both NPs exhibited superior efficacy in reducing IL-1β and JAK1 levels and upregulating Nrf2 expression compared to formulations with only one NP type. This innovative combination strategy demonstrates promise as a novel therapeutic approach for AD.

特应性皮炎（AD）是一种具有复杂发病机制的炎症性皮肤病。目前的临床治疗表现出一些局限性，包括低疗效和相当大的副作用，促使人们对新的治疗策略越来越感兴趣。在这项研究中，我们开发了一种微针辅助的双纳米药物递送策略，该策略同时针对氧化应激和Janus激酶1 （JAK1）表达，旨在增强AD的治疗。结合表没食子儿茶素没食子酸酯（EGCG）和乳铁蛋白的自组装纳米颗粒（NPs）被开发用于有效调节氧化应激。同时，利用CRISPR-CasRx技术沉默JAK1，并将CasRx和siRNA包埋在聚β-氨基酯（PBAE）中构建纳米颗粒。两种类型的NPs都通过微针成功地递送到AD小鼠的皮肤病变处，无论是单独的还是联合的，都显著减轻了症状。治疗减轻了皮炎严重程度评分和脾肿大，减少了表皮厚度和肥大细胞浸润，增加了胶原纤维含量。此外，背侧皮肤组织炎症因子（IL-1β、IL-4、IL-13）和氧化DNA损伤标志物（8-OHdG）水平降低，血清胸腺基质淋巴生成素（TSLP）和IgE水平降低。该疗法还抑制了JAK1的表达，激活了核因子红细胞2相关因子2 (Nrf2)/血红素加氧酶1 （HO-1）抗氧化途径，但pbae -质粒np负载微针没有显著增加HO-1的表达。值得注意的是，与仅含有一种NP类型的微针相比，含有两种NP类型的微针在降低IL-1β和JAK1水平以及上调Nrf2表达方面表现出更高的功效。这种创新的联合策略显示了作为一种新的治疗阿尔茨海默病的方法的希望。

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引用次数: 0