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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
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
{"title":"Bimetallic nanoadjuvant-mediated glutamine metabolism intervention and STING activation for enhanced antitumor immunity","authors":"Jiashi Zhang ,&nbsp;Chunzheng Yang ,&nbsp;Jia Tan ,&nbsp;Bin Liu ,&nbsp;Zhuang Yang ,&nbsp;Ziyao Li ,&nbsp;Jie Ma ,&nbsp;Meifang Wang ,&nbsp;Binbin Ding ,&nbsp;Abdulaziz A. Al Kheraif ,&nbsp;Ping’an Ma ,&nbsp;Jun Lin","doi":"10.1016/j.nantod.2025.102866","DOIUrl":"10.1016/j.nantod.2025.102866","url":null,"abstract":"<div><div>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 Mn<sup>2</sup><sup>+</sup> 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.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102866"},"PeriodicalIF":10.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Disassembly-driven turn-on fluorescent nanoprobe with adaptive signal amplification for quantitative carbonic anhydrase detection in whole blood and enhanced cancer imaging","authors":"Tenglong Zou ,&nbsp;Ye Chen ,&nbsp;Suanquan He ,&nbsp;Huiling Huang ,&nbsp;Zhiyang Yuwen ,&nbsp;Dailiang Zhang ,&nbsp;Lemeng Zhang ,&nbsp;Hongwen Liu","doi":"10.1016/j.nantod.2025.102869","DOIUrl":"10.1016/j.nantod.2025.102869","url":null,"abstract":"<div><div>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 (<strong>SQ-H-SA</strong>) leveraging self-assembly, recognition-driven activation, and adaptive signal amplification. <strong>SQ-H-SA</strong> 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. <strong>SQ-H-SA</strong> 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, <strong>SQ-H-SA</strong> achieves reliable quantification of endogenous CAs. Notably, <strong>SQ-H-SA</strong> 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, <strong>SQ-H-SA</strong> achieves the first selective, cell membrane-specific fluorescence imaging of CA Ⅸ in cancer cells and clinical lung cancer tissues.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102869"},"PeriodicalIF":10.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Aquaporin encoding mRNA mediated water bomb vaccine for cancer immunotherapy","authors":"Danhua Zhou ,&nbsp;Bin Wang ,&nbsp;Jiahui Gao ,&nbsp;Ruiying Wu ,&nbsp;Yuanji Feng ,&nbsp;Kai Hao ,&nbsp;Cong Liu ,&nbsp;Shasha He ,&nbsp;Ruonan Wang ,&nbsp;Yanhui Li ,&nbsp;Huayu Tian","doi":"10.1016/j.nantod.2025.102864","DOIUrl":"10.1016/j.nantod.2025.102864","url":null,"abstract":"<div><div>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 <em>in situ</em>, 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.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102864"},"PeriodicalIF":10.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Rubber-band-like polymeric nanotoroids’ preparation and their agile effects in anticancer drug delivery","authors":"Wen-Ping Jiang ,&nbsp;Yi-Chun Chen ,&nbsp;Ya-Yu Chiang ,&nbsp;Chung-Ping Yu ,&nbsp;Hui-Chang Lin ,&nbsp;Jiann-Yeu Chen ,&nbsp;Guan-Jhong Huang ,&nbsp;Hsin-Cheng Chiu ,&nbsp;Chieh-Yu Chung ,&nbsp;Min-Tsang Hsieh ,&nbsp;Yi-Ting Chiang","doi":"10.1016/j.nantod.2025.102862","DOIUrl":"10.1016/j.nantod.2025.102862","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102862"},"PeriodicalIF":10.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Antimicrobial effects of fibrous unit in modular self-assembling peptides","authors":"Jun-Xiao Yuan ,&nbsp;Yu-Juan Gao ,&nbsp;Rongrong Hua ,&nbsp;Tian-Ci Wei ,&nbsp;Guo-Yang Xu ,&nbsp;Jin Zhou ,&nbsp;Kuo Zhang ,&nbsp;Yu-Ting Li ,&nbsp;Jia-Qi Feng ,&nbsp;Wen-Jia Lai ,&nbsp;Lei Wang ,&nbsp;Xiaoxia Chen","doi":"10.1016/j.nantod.2025.102860","DOIUrl":"10.1016/j.nantod.2025.102860","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102860"},"PeriodicalIF":10.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Provoking endogenous protein-derived Zn2+ de-hijacking for metalloimmunotherapy","authors":"Anjun Song ,&nbsp;Wenjie Wang ,&nbsp;Yanjun Ji ,&nbsp;Heying Yuan ,&nbsp;Yanjie Zhang ,&nbsp;Jinsong Ren ,&nbsp;Xiaogang Qu","doi":"10.1016/j.nantod.2025.102867","DOIUrl":"10.1016/j.nantod.2025.102867","url":null,"abstract":"<div><div>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 Zn<sup>2+</sup> 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 Zn<sup>2+</sup>, thereby promoting STING activation without necessitating additional metal uptake. Overall, this work provides a safe and promising strategy for the development of metalloimmunotherapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102867"},"PeriodicalIF":10.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144826452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Corrigendum to “Scalable liposomes functionalization via membrane lipid exchange mechanisms” [Nano Today 61 (2025) 102630]","authors":"Xizi Long ,&nbsp;Chiho Kataoka-Hamai ,&nbsp;Chia-Lun Ho ,&nbsp;Wei-Lun Huang ,&nbsp;Yi-Ho Kuo ,&nbsp;Li-Ting Yang ,&nbsp;Wei-Peng Li ,&nbsp;Akihiro Okamoto","doi":"10.1016/j.nantod.2025.102859","DOIUrl":"10.1016/j.nantod.2025.102859","url":null,"abstract":"","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102859"},"PeriodicalIF":10.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"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]","authors":"Miao Ao ,&nbsp;Hongyi Hou ,&nbsp;He Zhang ,&nbsp;Lingpu Zhang ,&nbsp;Haihua Xiao ,&nbsp;Dan Zhao ,&nbsp;Kun Shang ,&nbsp;Bin Li","doi":"10.1016/j.nantod.2025.102855","DOIUrl":"10.1016/j.nantod.2025.102855","url":null,"abstract":"","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102855"},"PeriodicalIF":10.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"Metalamino acid framework (MAF)-mediated macrophage depletion and reprogramming for arthritis treatment","authors":"Rui-Qi Li ,&nbsp;Jing-Yi Zhang ,&nbsp;Yi-Bo Zhang ,&nbsp;Jin Dai ,&nbsp;Jin Hong ,&nbsp;Ya Ding","doi":"10.1016/j.nantod.2025.102856","DOIUrl":"10.1016/j.nantod.2025.102856","url":null,"abstract":"<div><div>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 metal<img>amino acid framework (MAF) system with dual functions of methotrexate (MTX) delivery and reactive oxygen species (ROS) clearance. Specifically, Zn<sup>2 +</sup> 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.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102856"},"PeriodicalIF":10.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
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
{"title":"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","authors":"Nikolaos Tagaras ,&nbsp;Haihan Song ,&nbsp;Giacomo Reina ,&nbsp;Sandro Lehner ,&nbsp;Vera M. Kissling ,&nbsp;Alexander Gogos ,&nbsp;Weijun Tong ,&nbsp;Tina Buerki-Thurnherr","doi":"10.1016/j.nantod.2025.102857","DOIUrl":"10.1016/j.nantod.2025.102857","url":null,"abstract":"<div><div>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 <em>in vitro</em>. We engineered a PCN224 MOF, composed of zirconium clusters (Zr<sub>6</sub>) and 4-carboxyphenyl-porphyrin (H<sub>2</sub>TCPP), 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 <em>in vitro</em> 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.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102857"},"PeriodicalIF":10.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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