Nano Today最新文献_第9页

Bimetallic nanoadjuvant-mediated glutamine metabolism intervention and STING activation for enhanced antitumor immunity 双金属纳米佐剂介导的谷氨酰胺代谢干预和STING激活增强抗肿瘤免疫

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-15 DOI: 10.1016/j.nantod.2025.102866

Jiashi Zhang , Chunzheng Yang , Jia Tan , Bin Liu , Zhuang Yang , Ziyao Li , Jie Ma , Meifang Wang , Binbin Ding , Abdulaziz A. Al Kheraif , Ping’an Ma , Jun Lin

Immune evasion induced by tumor metabolic reprogramming and the low immunogenicity of tumors resulting in insufficient antitumor immune responses have severely hindered the efficacy of immunotherapy. Herein, we design a bimetallic immunoadjuvant with infinite coordination based on Fe and Mn ions as metal connection points, loaded with the glutamine antagonist diazooxonorleucine (DON), to initiate a robust systemic immune response by targeting glutamine metabolism and activating the stimulator of interferon genes (STING) pathway. The nanoadjuvant exhibits stronger capabilities for generating hydroxyl radicals and depleting glutathione, effectively inducing ferroptosis and immunogenic cell death (ICD). Ingeniously, remarkable ferroptosis amplifies oxidative stress and promotes the generation and cytoplasmic leakage of dsDNA, which acts as an immune-enhancing agent synergistically with Mn²⁺ to trigger the cGAS-STING innate immune pathway. Moreover, this nanoadjuvant can inhibit glutamine metabolism, thereby reversing the immunosuppressive microenvironment and restoring immune cell function while disrupting the redox homeostasis and energy supply of tumor cells, which further sensitizes ferroptosis. Overall, this cascade-enhanced immunotherapy strategy achieves a broader spectrum of immunotherapy by closely combining innate and adaptive immunity via the intervention of glutamine metabolism and ferroptosis. This study facilitates the progress of amino acid metabolism regulation-based cancer therapy and offers a promising treatment strategy for enhancing antitumor immunity.

肿瘤代谢重编程诱导的免疫逃避和肿瘤低免疫原性导致的抗肿瘤免疫应答不足严重阻碍了免疫治疗的效果。在此，我们设计了一种以铁和锰离子为金属连接点的无限配位双金属免疫佐剂，负载谷氨酰胺拮抗剂重氮异诺亮氨酸（DON），通过靶向谷氨酰胺代谢和激活干扰素基因刺激因子（STING）途径来启动强大的全身免疫反应。纳米佐剂具有较强的羟基自由基生成和谷胱甘肽消耗能力，可有效诱导铁凋亡和免疫原性细胞死亡（ICD）。显著的铁凋亡巧妙地放大氧化应激，促进dsDNA的产生和细胞质渗漏，dsDNA作为免疫增强剂与Mn2+协同触发cGAS-STING先天免疫途径。此外，该纳米佐剂可以抑制谷氨酰胺代谢，从而逆转免疫抑制微环境，恢复免疫细胞功能，同时破坏肿瘤细胞的氧化还原稳态和能量供应，进一步致敏铁凋亡。总的来说，这种级联增强的免疫治疗策略通过谷氨酰胺代谢和铁凋亡的干预，将先天免疫和适应性免疫紧密结合，实现了更广泛的免疫治疗。本研究促进了基于氨基酸代谢调节的癌症治疗的进展，为增强抗肿瘤免疫提供了一种有前景的治疗策略。

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引用次数: 0

Disassembly-driven turn-on fluorescent nanoprobe with adaptive signal amplification for quantitative carbonic anhydrase detection in whole blood and enhanced cancer imaging 具有自适应信号放大的可拆卸驱动的荧光纳米探针用于全血中碳酸酐酶的定量检测和增强癌症成像

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-14 DOI: 10.1016/j.nantod.2025.102869

Tenglong Zou , Ye Chen , Suanquan He , Huiling Huang , Zhiyang Yuwen , Dailiang Zhang , Lemeng Zhang , Hongwen Liu

Carbonic anhydrases (CAs), particularly CA Ⅸ, are critical biomarkers in cancer diagnosis and therapy, but quantitative detection in whole blood remains challenging due to intrinsic background fluorescence, limited signal amplification, and interference from blood autofluorescence. Here, we introduce a disassembly-driven fluorescent nanoprobe (SQ-H-SA) leveraging self-assembly, recognition-driven activation, and adaptive signal amplification. SQ-H-SA harnesses squaraine (SQ) dyes that self-assemble into stable, fluorescence-quenched aggregates in aqueous solution; upon CAs binding, the nanoprobe disassembles, enabling SQ monomers to become conformationally shielded within the protein’s hydrophobic pocket, achieving a rapid 45-fold fluorescence enhancement within minutes of interaction with 3 μM CA Ⅸ. SQ-H-SA nanoprobe exhibits good selectivity (with limited interference from serum albumin), sub-nanomolar sensitivity, and large signal-to-background ratio, enabled by ultralow intrinsic fluorescence and protein-assisted amplification. By effectively suppressing blood autofluorescence based on the inner filter effect, SQ-H-SA achieves reliable quantification of endogenous CAs. Notably, SQ-H-SA not only detected elevated CAs levels in untreated lung cancer patients and notable posttreatment reductions consistent with ELISA findings, but also facilitated high-throughput analysis of clinical specimens to improve diagnostic precision in liquid biopsies. Moreover, SQ-H-SA achieves the first selective, cell membrane-specific fluorescence imaging of CA Ⅸ in cancer cells and clinical lung cancer tissues.

碳酸酐酶（CA），特别是CAⅨ，是癌症诊断和治疗中的关键生物标志物，但由于其固有的背景荧光、有限的信号放大和血液自身荧光的干扰，在全血中进行定量检测仍然具有挑战性。在这里，我们介绍了一种分解驱动的荧光纳米探针（SQ-H-SA），利用自组装、识别驱动激活和自适应信号放大。SQ- h - sa利用squaraine （SQ）染料在水溶液中自组装成稳定的荧光猝灭聚集体；在CAs结合后，纳米探针分解，使SQ单体在蛋白质的疏水口袋内成为构象屏蔽，在与3 μ CAⅨ相互作用的几分钟内实现了45倍的荧光增强。SQ-H-SA纳米探针具有良好的选择性（受血清白蛋白的干扰有限），亚纳摩尔灵敏度和大的信本比，通过超低的固有荧光和蛋白质辅助扩增实现。SQ-H-SA基于内部过滤效应有效抑制血液自身荧光，实现内源性CAs的可靠定量。值得注意的是，SQ-H-SA不仅检测到未经治疗的肺癌患者中CAs水平升高，而且与ELISA结果一致，治疗后显著降低，而且有助于临床标本的高通量分析，以提高液体活检的诊断精度。此外，SQ-H-SA在癌细胞和临床肺癌组织中首次实现了CAⅨ的选择性、细胞膜特异性荧光成像。

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引用次数: 0

Aquaporin encoding mRNA mediated water bomb vaccine for cancer immunotherapy 水通道蛋白编码mRNA介导的肿瘤免疫治疗水弹疫苗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-14 DOI: 10.1016/j.nantod.2025.102864

Danhua Zhou , Bin Wang , Jiahui Gao , Ruiying Wu , Yuanji Feng , Kai Hao , Cong Liu , Shasha He , Ruonan Wang , Yanhui Li , Huayu Tian

Inducing immunogenic cell death (ICD) in tumors is a promising strategy for activating systemic antitumor immunity. However, most ICD approaches rely on chemotherapeutic or physical agents that pose challenges in controllability and biosafety. Here, we report a drug-free, mRNA-based strategy that induces a novel form of ICD via a “water bomb” effect. By delivering aquaporin mRNA into tumor cells using nucleic acid nanocarriers, aquaporins are expressed and embedded in the tumor cell membrane. Upon modulation of the transmembrane osmotic gradient, water influx is rapidly amplified through aquaporin channels, leading to extreme cellular swelling, complete membrane rupture, and explosive tumor cell lysis. This unique form of endogenously driven mechanical ICD elicits potent immune activation by concurrently releasing a full spectrum of damage-associated molecular patterns (DAMPs), tumor-specific antigens, and neoantigens in situ, thereby promoting efficient activation of bone marrow-derived dendritic cells (BMDCs) and enhancing subsequent antigen presentation. In a murine melanoma model, this strategy significantly inhibited the growth of both primary and distant tumors, as well as lung metastases. Similarly, in a breast cancer mouse model, it markedly suppressed the growth of subcutaneous tumors. With excellent biocompatibility, tunability, and immune potency, this “water bomb” based approach offers a conceptually new paradigm for cancer immunotherapy via endogenously driven mechanical ICD.

在肿瘤中诱导免疫原性细胞死亡（ICD）是一种很有前途的激活全身抗肿瘤免疫的策略。然而，大多数ICD方法依赖于化疗或物理药物，这在可控性和生物安全性方面构成挑战。在这里，我们报告了一种无药物、基于mrna的策略，通过“水弹”效应诱导一种新型的ICD。利用核酸纳米载体将水通道蛋白mRNA传递到肿瘤细胞中，实现水通道蛋白在肿瘤细胞膜上的表达和包埋。在跨膜渗透梯度的调节下，水通过水通道蛋白通道流入迅速放大，导致细胞极端肿胀，膜完全破裂，肿瘤细胞爆发性溶解。这种独特的内源性驱动机械ICD通过同时释放全谱损伤相关分子模式（DAMPs）、肿瘤特异性抗原和原位新抗原，从而促进骨髓源性树突状细胞（bmdc）的有效激活，并增强随后的抗原呈递，从而引发有效的免疫激活。在小鼠黑色素瘤模型中，该策略显著抑制了原发肿瘤和远处肿瘤以及肺转移瘤的生长。同样，在乳腺癌小鼠模型中，它显著抑制了皮下肿瘤的生长。这种基于“水弹”的方法具有良好的生物相容性、可调性和免疫效力，为通过内源性驱动的机械ICD进行癌症免疫治疗提供了概念上的新范例。

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引用次数: 0

Rubber-band-like polymeric nanotoroids’ preparation and their agile effects in anticancer drug delivery 类橡皮筋聚合物纳米环的制备及其在抗癌药物传递中的敏捷作用

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-12 DOI: 10.1016/j.nantod.2025.102862

Wen-Ping Jiang , Yi-Chun Chen , Ya-Yu Chiang , Chung-Ping Yu , Hui-Chang Lin , Jiann-Yeu Chen , Guan-Jhong Huang , Hsin-Cheng Chiu , Chieh-Yu Chung , Min-Tsang Hsieh , Yi-Ting Chiang

In this study, an agile anticancer drug-conjugatable toroidal mixed micelle (TMM) platform was developed. When observed under a high-speed real-time microscope, the drug-loaded TMMs exhibited dynamic transformation, displaying rubber-band-like characteristics under both static and flow conditions. Microscopic observations revealed that the spherical mixed micelles (SMMs) were internalized by cells upon their attachment in a static state or under flow conditions, whereas the TMMs were taken up by the cells only when coming into contact with expanding surfaces during their dynamic transformation. This effect resulted in a reduction in the total cellular uptake of TMMs by macrophage cells. In addition, the agile effect of TMMs affords them an exceptional ability to penetrate tumor spheroids in a static state and imparts exceptional extrusive ability when they flow through small pores. The in vivo studies conducted in this work demonstrate their superior ability to penetrate ruptured blood vessels, accumulate in tumor lesions, and avoid macrophage uptake into the liver or spleen. These in vivo studies also indicate that the TMMs eliminated cancerous cells deep within tumors while causing no injury to the liver and spleen, while SMMs displayed suboptimal tumor inhibition, due to their deposits in the proximity of blood vessels. Our TMM platform is feasible as a drug delivery system in anticancer applications.

在这项研究中，开发了一种灵活的抗癌药物共轭环形混合胶束（TMM）平台。在高速实时显微镜下观察，载药TMMs在静态和流动条件下均呈现出橡皮筋样的动态变化。微观观察表明，在静态或流动条件下，球形混合胶束（SMMs）在附着时被细胞内化，而在动态转化过程中，TMMs只有在与膨胀表面接触时才被细胞吸收。这种效应导致巨噬细胞对TMMs的总细胞摄取减少。此外，TMMs的敏捷效应使其具有在静态状态下穿透肿瘤球体的特殊能力，并在流过小孔隙时具有特殊的挤出能力。本工作进行的体内研究表明，它们具有穿透破裂血管，在肿瘤病变中积聚，避免巨噬细胞摄取到肝脏或脾脏的优越能力。这些体内研究还表明，TMMs消除肿瘤深处的癌细胞，同时不会对肝脏和脾脏造成损伤，而SMMs由于其沉积在血管附近，表现出次优的肿瘤抑制作用。我们的TMM平台作为一种抗癌药物传递系统是可行的。

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引用次数: 0

Antimicrobial effects of fibrous unit in modular self-assembling peptides 模块化自组装肽中纤维单元的抗菌作用

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-11 DOI: 10.1016/j.nantod.2025.102860

Jun-Xiao Yuan , Yu-Juan Gao , Rongrong Hua , Tian-Ci Wei , Guo-Yang Xu , Jin Zhou , Kuo Zhang , Yu-Ting Li , Jia-Qi Feng , Wen-Jia Lai , Lei Wang , Xiaoxia Chen

The strategy of using modular self-assembling peptides (MSAPs) forming nanofibers (NFs) in the "recognition-capture" antibacterial process has gained significant attention. In this study, we developed a series of MSAPs and investigated the structural determinants governing their antibacterial efficacy, with a focus on the β-sheet content and nanofiber mechanics. The variation in β-sheet content (Δβ-sheet) of MSAPs after incubation with lipopolysaccharides (LPS) was contingent on the peptide structure of the fibrous subunits. A pronounced negative correlation was observed between Δβ-sheet and the minimum inhibitory concentration (MIC), indicating that enhanced β-sheet content directly potentiated antimicrobial activity. Furthermore, the Young’s modulus of the NFs was quantitatively characterized by AFM, exhibited an inverse relationship with MIC values. This suggests that the higher Young’s modulus of NFs confer superior bacterial inhibition. Meanwhile, we demonstrated that MSAPs at concentrations lower than MIC possess strong anti-infection potential. It was found that the NFs of MSAPs with hydrophilic fibrous units entangled around the bacteria more than hydrophobic ones, showing higher invasion inhibition of bacteria to host cells. This understanding of the antimicrobial activity of MSAPs may help us design more effective antibacterial peptides.

在“识别-捕获”抗菌过程中使用模块化自组装肽（masp）形成纳米纤维（NFs）的策略受到了广泛关注。在这项研究中，我们开发了一系列masp，并研究了控制其抗菌效果的结构决定因素，重点研究了β-片含量和纳米纤维力学。masp与脂多糖（LPS）孵育后β-薄片含量（Δβ-sheet）的变化取决于纤维亚基的肽结构。Δβ-sheet与最低抑菌浓度（MIC）呈显著负相关，表明β-sheet含量的增加直接增强了抗菌活性。此外，用AFM定量表征了NFs的杨氏模量，并与MIC值呈反比关系。这表明，NFs的杨氏模量较高，具有较好的细菌抑制作用。同时，我们证明了低于MIC浓度的msps具有很强的抗感染潜力。结果发现，具有亲水性纤维单元的msap的NFs比疏水性msap的NFs更缠绕在细菌周围，显示出更高的细菌对宿主细胞的侵袭抑制作用。对MSAPs抗菌活性的了解有助于我们设计出更有效的抗菌肽。

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引用次数: 0

Provoking endogenous protein-derived Zn2+ de-hijacking for metalloimmunotherapy 激发内源性蛋白衍生的Zn2+解劫持用于金属免疫治疗

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-11 DOI: 10.1016/j.nantod.2025.102867

Anjun Song , Wenjie Wang , Yanjun Ji , Heying Yuan , Yanjie Zhang , Jinsong Ren , Xiaogang Qu

Metalloimmunotherapy involves utilizing metal ions to achieve promising immunotherapy. However, the exogenous metal ions may cause unexpected severe side effects in metalloimmunotherapy due to the unstable and non-specific characteristics of nanomaterials. Herein, drawing inspiration from the utilization of endogenous intracellular Zn-storing proteins, a nonmetallic nanodrug has been developed to induce the endogenous protein-derived Zn²⁺ de-hijacking for metalloimmunotherapy. Specifically, the nonmetallic nanodrug was designed using disulfide-doped hollow organosilicon co-loaded with 5-aminolevulinic acid and glutathione-responsive nitric oxide (NO) donor (NIC), functioning as a STING activator. Upon internalization, subsequent near-infrared laser irradiation can prompt the STING activator to elicit mitochondrial impairment and discharge mitochondrial DNA, thereby initiating the STING pathway. Simultaneously, the interplay between NIC and glutathione results in the production of NO to induce the liberation of protein-derived Zn²⁺, thereby promoting STING activation without necessitating additional metal uptake. Overall, this work provides a safe and promising strategy for the development of metalloimmunotherapy.

金属免疫疗法是利用金属离子实现有前景的免疫治疗。然而，由于纳米材料的不稳定性和非特异性，外源金属离子可能在金属免疫治疗中引起意想不到的严重副作用。本文从内源性细胞内锌储存蛋白的利用中获得灵感，开发了一种非金属纳米药物来诱导内源性蛋白衍生的Zn2+解劫持用于金属免疫治疗。具体来说，该非金属纳米药物是用二硫化物掺杂的空心有机硅与5-氨基乙酰丙酸和谷胱甘肽响应型一氧化氮（NO）供体（NIC）共负载，作为STING激活剂来设计的。内化后，随后的近红外激光照射可促使STING激活剂引起线粒体损伤并释放线粒体DNA，从而启动STING通路。同时，NIC和谷胱甘肽之间的相互作用导致NO的产生，从而诱导蛋白质衍生的Zn2+的释放，从而促进STING激活，而不需要额外的金属摄取。总之，这项工作为金属免疫治疗的发展提供了一个安全而有前途的策略。

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引用次数: 0

Corrigendum to “Scalable liposomes functionalization via membrane lipid exchange mechanisms” [Nano Today 61 (2025) 102630] “通过膜脂交换机制实现可扩展脂质体功能化”的更正[Nano Today 61 (2025) 102630]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-06 DOI: 10.1016/j.nantod.2025.102859

Xizi Long , Chiho Kataoka-Hamai , Chia-Lun Ho , Wei-Lun Huang , Yi-Ho Kuo , Li-Ting Yang , Wei-Peng Li , Akihiro Okamoto

引用次数: 0

Corrigendum to “GSH-responsive nanoparticles enhance ovarian cancer chemo-immunotherapy via DNA damage repair pathway inhibition and cGAS-STING pathway activation” [Nano Today 62 (2025) 102729] “gsh反应性纳米颗粒通过DNA损伤修复途径抑制和cGAS-STING途径激活增强卵巢癌化学免疫治疗”的勘误[Nano Today 62 (2025) 102729]

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-05 DOI: 10.1016/j.nantod.2025.102855

Miao Ao , Hongyi Hou , He Zhang , Lingpu Zhang , Haihua Xiao , Dan Zhao , Kun Shang , Bin Li

引用次数: 0

Metalamino acid framework (MAF)-mediated macrophage depletion and reprogramming for arthritis treatment 元氨基酸框架（MAF）介导的巨噬细胞耗竭和重编程治疗关节炎

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-08-04 DOI: 10.1016/j.nantod.2025.102856

Rui-Qi Li , Jing-Yi Zhang , Yi-Bo Zhang , Jin Dai , Jin Hong , Ya Ding

Inflammatory M1 macrophages play a crucial role in the pathogenesis of rheumatoid arthritis (RA). However, the simultaneous depletion and reprogramming of M1 macrophages in RA therapy remains a significant challenge. To address this issue, we developed a macrophage-targeting metalamino acid framework (MAF) system with dual functions of methotrexate (MTX) delivery and reactive oxygen species (ROS) clearance. Specifically, Zn^2 + ions and 9-fluorenylmethyloxycarbonyl-modified histidine (Fmoc-H) form a framework structure (pZFH) through coordination. The Fmoc-His-Thr-Lys-Pro-Arg peptide (Fmoc-HTKPR) can be easily doped into this structure at different ratios to modulate its targeting ability. MTX and Pt nanodots are loaded into the system by incorporating MTX during the pZFH preparation process and reducing platinum salts adsorbed on the surface of the pZFH-MTX nanoparticles (NPs). The targeting peptide enhanced the recognition and uptake of NPs by inflammatory macrophages. The release of MTX in response to the acidic inflammatory environment controls macrophage proliferation, while the Pt nanodots eliminated ROS, thereby promoting the polarization of proinflammatory M1 macrophages towards anti-inflammatory M2 macrophages. In an RA model, pZFH-MTX-Pt significantly reduced the expression of proinflammatory cytokines TNF-α and IL-6, alleviated joint swelling, and decreased bone hyperplasia. This system thus provides a synergistic RA treatment strategy that combines chemotherapy and immunotherapy.

炎性M1巨噬细胞在类风湿关节炎（RA）的发病机制中起着至关重要的作用。然而，在RA治疗中M1巨噬细胞的同时耗竭和重编程仍然是一个重大挑战。为了解决这个问题，我们开发了一个巨噬细胞靶向的金属氨基酸框架（MAF）系统，具有甲氨蝶呤（MTX）递送和活性氧（ROS）清除的双重功能。具体来说，Zn2 +离子与9-氟酰甲基羰基修饰组氨酸（Fmoc-H）通过配位形成框架结构（pZFH）。Fmoc-His-Thr-Lys-Pro-Arg肽（Fmoc-HTKPR）可以很容易地以不同的比例掺杂到该结构中，以调节其靶向能力。通过在pZFH制备过程中加入MTX，并还原吸附在pZFH-MTX纳米颗粒（NPs）表面的铂盐，将MTX和Pt纳米点加载到系统中。靶向肽增强了炎性巨噬细胞对NPs的识别和摄取。MTX在酸性炎症环境下的释放控制了巨噬细胞的增殖，而Pt纳米点消除了ROS，从而促进了促炎M1巨噬细胞向抗炎M2巨噬细胞的极化。在RA模型中，pZFH-MTX-Pt可显著降低促炎因子TNF-α和IL-6的表达，减轻关节肿胀，减少骨质增生。因此，该系统提供了一种结合化疗和免疫治疗的协同治疗策略。

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引用次数: 0

Broken but not beaten: Unraveling the biotransformation fate of Mn@PCN224 nanozymes and its influence on enzymatic activity and safety at the human placenta in vitro 破碎但未被打败：揭示Mn@PCN224纳米酶的生物转化命运及其对体外人胎盘酶活性和安全性的影响

IF 10.9 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Today

Pub Date : 2025-07-31 DOI: 10.1016/j.nantod.2025.102857

Nikolaos Tagaras , Haihan Song , Giacomo Reina , Sandro Lehner , Vera M. Kissling , Alexander Gogos , Weijun Tong , Tina Buerki-Thurnherr

Chronic placental inflammation has been associated with severe pregnancy complications including miscarriage, stillbirth, premature delivery, intra-uterine growth restriction, and recurrence risk in future pregnancies. Treatments are essential, but current standard therapies for infections and inflammation often struggle with limited efficacy and potential side effects. Nanomaterials with enzyme-mimetic properties (nanozymes) have demonstrated impressive medical capabilities especially in inflammation treatment. Remarkably, single-atom nanozymes (SAzymes) including metal-organic frameworks (MOFs) have attracted considerable attention due to their superior substrate affinity and catalytic activity compared to conventional nanozymes. However, due to their high reactivity, nanozymes could undergo biotransformation in biological fluids and tissues, affecting their physicochemical properties and potentially compromising their therapeutic efficacy and safety. On this basis, we performed a systematic study on the chemical and structural biotransformation, catalytic activity and biological impact of a PCN224 MOF at the human placenta in vitro. We engineered a PCN224 MOF, composed of zirconium clusters (Zr₆) and 4-carboxyphenyl-porphyrin (H₂TCPP), further doping it with Mn (Mn@PCN224) to form Mn-TCPP complexes. These complexes mimic the natural Mn-superoxide dismutase (MnSOD), a crucial enzyme to detoxify cells from radical stress during inflammation. In biological media, Mn@PCN224 underwent rapid and substantial decomposition, leading to a significant release of Mn-TCPP complexes. Nonetheless, despite the observed biotransformation, the SOD activity was maintained, mostly by the free Mn-TCPP bearing the enzyme-like active center. We further revealed that Mn@PCN224 SAzymes and their biotransformation products did not compromise cell viability, barrier integrity and endocrine function in an in vitro human placenta co-culture model. The current findings provide crucial insights about the biotransformation mechanism of a MOF-based SAzyme and emphasize the importance of biostability assessment, in addition to efficacy and safety evaluation.

慢性胎盘炎症与严重的妊娠并发症有关，包括流产、死胎、早产、子宫内生长受限和未来妊娠的复发风险。治疗是必不可少的，但目前治疗感染和炎症的标准疗法往往疗效有限，而且有潜在的副作用。具有模拟酶特性的纳米材料（纳米酶）已经显示出令人印象深刻的医疗能力，特别是在炎症治疗方面。值得一提的是，包括金属有机框架（mof）在内的单原子纳米酶（SAzymes）由于其与传统纳米酶相比具有优越的底物亲和力和催化活性而引起了人们的广泛关注。然而，由于其高反应性，纳米酶可能在生物流体和组织中进行生物转化，影响其物理化学性质，并可能损害其治疗效果和安全性。在此基础上，我们对PCN224 MOF在体外人胎盘中的化学和结构生物转化、催化活性和生物学影响进行了系统研究。我们设计了一种PCN224 MOF，由锆簇（Zr6）和4-羧基苯基卟啉（H2TCPP）组成，并进一步与Mn （Mn@PCN224）掺杂形成Mn- tcpp配合物。这些复合物模拟了天然的锰超氧化物歧化酶（MnSOD），这是一种在炎症期间使细胞从自由基应激中解毒的关键酶。在生物培养基中，Mn@PCN224经历了快速而实质性的分解，导致Mn-TCPP复合物的大量释放。然而，尽管观察到生物转化，SOD活性仍然保持，主要是由带有酶样活性中心的游离Mn-TCPP维持。我们进一步发现Mn@PCN224 SAzymes及其生物转化产物在体外人胎盘共培养模型中不会损害细胞活力、屏障完整性和内分泌功能。目前的研究结果为基于mof的SAzyme的生物转化机制提供了重要的见解，并强调了除疗效和安全性评估外，生物稳定性评估的重要性。

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引用次数: 0