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Lipidic prodrug nanosponges deliver proteins for combination therapy of candida-biofilm infections
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-10 DOI: 10.1016/j.nantod.2025.102759
Yuanfeng Li , Yumeng Wang , Yinzi Piao , Huaping Li , Xinghong Zhao , Hongping Wan , Linzhu Su , Linqi Shi , Yong Liu
{"title":"Lipidic prodrug nanosponges deliver proteins for combination therapy of candida-biofilm infections","authors":"Yuanfeng Li ,&nbsp;Yumeng Wang ,&nbsp;Yinzi Piao ,&nbsp;Huaping Li ,&nbsp;Xinghong Zhao ,&nbsp;Hongping Wan ,&nbsp;Linzhu Su ,&nbsp;Linqi Shi ,&nbsp;Yong Liu","doi":"10.1016/j.nantod.2025.102759","DOIUrl":"10.1016/j.nantod.2025.102759","url":null,"abstract":"<div><div>Lipidic prodrug nanomedicines combine the benefits of nanoparticles and prodrugs, yet their use in conjunction with protein therapeutics has been restricted by the subpar loading and protective capabilities of traditional lipidic prodrug assemblies. To address this challenge, this study introduces lipidic prodrug nanosponges (LPNs) for the loading and protection of proteins, aiming for combination therapy of chemical and protein therapeutics. A ketoconazole-containing lipidic prodrug is synthesized via dynamic boronate bond formation and subjected to assemble to form the nanosponge structures. Regardless of their isoelectric points and molecular weights, proteins can be efficiently loaded into LPNs, achieving a loading efficiency of approximately 60 % due to multivalent interactions. Additionally, LPNs effectively shield proteins from degradation and enable controlled release. Subsequently, the representative DNase I-loaded LPNs effectively prevent the formation of Candida biofilm and destruct mature biofilms through the combined action of DNase I, which eliminates extracellular DNA in the biofilm matrix, thereby enhancing the antifungal efficacy of ketoconazole in combination. Furthermore, DNase I-loaded LPNs efficiently eradicate Candida biofilms and alleviate inflammation in murine models of oral candidosis and model candidal vaginitis, facilitating tissue remodeling. Overall, our LPNs offer an efficient and protective platform for protein delivery in combination therapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102759"},"PeriodicalIF":13.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814914","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
Zig-Zag cracking as a possible characteristic feature of hydrogen embrittlement in a low alloy steel: Insights from in-situ TEM studies
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-08 DOI: 10.1016/j.nantod.2025.102738
Lin Tian , Masanobu Kubota , Reiner Kirchheim , Cynthia A. Volkert
{"title":"Zig-Zag cracking as a possible characteristic feature of hydrogen embrittlement in a low alloy steel: Insights from in-situ TEM studies","authors":"Lin Tian ,&nbsp;Masanobu Kubota ,&nbsp;Reiner Kirchheim ,&nbsp;Cynthia A. Volkert","doi":"10.1016/j.nantod.2025.102738","DOIUrl":"10.1016/j.nantod.2025.102738","url":null,"abstract":"<div><div>Hydrogen embrittlement of steel poses a significant challenge to the development of a reliable and sustainable hydrogen-based energy future. Despite well-established phenomenology and widely discussed mechanisms, a defect-level understanding remains incomplete. Using in-situ environmental transmission electron microscopy, we tracked fracture in Cr-Mo low alloy steel lamellae and found that the presence of hydrogen gas fundamentally alters the fracture process. In the presence of hydrogen, sharp, facetted zig-zag cracks form in the thinned regions of the lamellae ahead of the crack tip, rapidly propagating with minimal plasticity. This contrasts with vacuum conditions, where cracks propagate more slowly by forming holes in the lamellae ahead of the crack tip, followed by extensive necking and rupture of the crack bridges between the holes. We propose two defect-level scenarios that account for our observations—based on hydrogen enhanced decohesion (HEDE) and hydrogen enhanced localized plasticity (HELP)— and challenge current modeling efforts to explore how hydrogen can account for the formation of zig-zag cracks in thin lamellae. Evidence for zig-zag cracking is also observed at the tear ridges on the of fracture surfaces hydrogen embrittled bulk samples, suggesting its role in the fracture process within crack bridges during bulk fracture. Considering the number and size of the crack bridges, we argue that zig-zag cracking may contribute to hydrogen embrittlement of bulk steels.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102738"},"PeriodicalIF":13.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tumor cell-derived engineered exosome enhances effective immunotherapy for orthotopic glioblastoma and its recurrences
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-08 DOI: 10.1016/j.nantod.2025.102748
Shanshan Li , Dongya Zhang , Yibin Wang , Muhammad Ismail , Wenya He , Meng Zheng , Bingyang Shi , Yan Zou
{"title":"Tumor cell-derived engineered exosome enhances effective immunotherapy for orthotopic glioblastoma and its recurrences","authors":"Shanshan Li ,&nbsp;Dongya Zhang ,&nbsp;Yibin Wang ,&nbsp;Muhammad Ismail ,&nbsp;Wenya He ,&nbsp;Meng Zheng ,&nbsp;Bingyang Shi ,&nbsp;Yan Zou","doi":"10.1016/j.nantod.2025.102748","DOIUrl":"10.1016/j.nantod.2025.102748","url":null,"abstract":"<div><div>Glioblastoma multiforme (GBM) is considered as one of the most lethal malignancies in the central neuron system (CNS). Despite significant advances in immunotherapy approaches for multiple tumors, the highly immunosuppressive tumor microenvironment (TME) of GBM presents critical challenges. Inspired by tumor-derived exosomes, which carry a range of tumor-associated antigens and possess improved blood-brain barrier (BBB) transcytosis, we have developed CpG adjuvant-functionalized GBM tumor-derived exosomes (Exo-CpG) to inhibit GBM proliferation and elicit long-lasting protective immunity via potent stimulation of the body's innate immunity. Our exosomal nanoplatform efficiently activates the antigen-presenting dendritic cells (DCs) in lymph nodes, promoting their maturation, and generating a strong T cell response. In combination with the anti-programmed cell death ligand-1 antibody (aPD-L1), these exosomes effectively restrain the growth of GBM in orthotopic primary GL261 and phosphatase and tensin homologue (PTEN)-deficient immunosuppressive CT2A models in immune-competent mice, significantly prolonging survival by effectively suppressing GBM recurrence. This fully natural exosomal nanoplatform offers a promising strategy for targeting the immunosuppressive TME of orthotopic primary GBM and its recurrences.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102748"},"PeriodicalIF":13.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143792317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-molecule light-scattering imaging for in situ counting circular RNA
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102743
Hao Wang , Xin Liu , Pengbo Zhang , Ke Qin , Shen Ling , Xiaoyu Wang , Fangfang Wang , Zhengping Li
{"title":"Single-molecule light-scattering imaging for in situ counting circular RNA","authors":"Hao Wang ,&nbsp;Xin Liu ,&nbsp;Pengbo Zhang ,&nbsp;Ke Qin ,&nbsp;Shen Ling ,&nbsp;Xiaoyu Wang ,&nbsp;Fangfang Wang ,&nbsp;Zhengping Li","doi":"10.1016/j.nantod.2025.102743","DOIUrl":"10.1016/j.nantod.2025.102743","url":null,"abstract":"<div><div>The detection of circular RNA (circRNA) at the single-molecule level is essential for the elucidation of circRNA-mediated signaling pathways and its association with disease. Although many fluorescence-based methods have been used for the <em>in situ</em> imaging of circRNA, the inherent defects of fluorescent dyes, including high background signal and photobleaching, preclude sensitivity to the single-molecule level. Herein, leveraging the microRNA sponge feature of circRNA and the strong light-scattering signals of gold nanoparticles (AuNPs), we develop a circRNA-induced assembling of plasmon-coupled spherical nucleic acids (SNAs) strategy for in situ light-scattering imaging and counting of circRNA at the single-molecule level. The SNAs were constructed by modifying sponge probes on AuNPs, which were small and initially invisible. The microRNA sponge nature of circRNA led to the assembly of SNAs to form AuNP aggregates with enhanced light-scattering signals, which could be visualized as diffraction-limited spots irrespective of the interference signals produced by the intracellular environment. This method enabled the accurate quantification of the circRNA by counting the number of spots from a zero background, facilitating the <em>in situ</em> imaging and counting of individual circRNAs at the single-molecule level.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102743"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777136","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
Morphology-driven UV photodetection in self-powered Pt/ZnO Schottky devices
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102754
Xiaohu Chen , Binesh Puthen Veettil , Noushin Nasiri
{"title":"Morphology-driven UV photodetection in self-powered Pt/ZnO Schottky devices","authors":"Xiaohu Chen ,&nbsp;Binesh Puthen Veettil ,&nbsp;Noushin Nasiri","doi":"10.1016/j.nantod.2025.102754","DOIUrl":"10.1016/j.nantod.2025.102754","url":null,"abstract":"<div><div>Emerging nanostructured materials have opened new frontiers in the design of high-performance optoelectronic devices, particularly for self-powered photodetection applications. Here, we present the novel self-powered UV photodetection capabilities of Pt/ZnO Schottky barrier devices that fabricated with two distinct ZnO morphologies: dendrite-like nanoclusters (DNCs) and nano- micro-cluster arrays (NMCAs). Both architectures demonstrate robust self-powered UV photodetection performance, albeit with significant differences in their optoelectronic behavior. The DNC-based UV photodetector (Pt/ZnO<sub>DNCs</sub>), characterized by weak inter-nanoparticle connections and smaller structural dimensions, exhibits reduced photocurrent, higher noise levels, and non-linear photoresponse dynamics under elevated UV illumination. Conversely, the NMCA-based devices (Pt/ZnO<sub>NMCAs</sub>), formed through capillary-driven self-assembly of DNCs using a single ethanol droplet, achieve a dramatic enhancement in performance, with a nearly thousand-fold increase in photocurrent, alongside excellent repeatability and long-term stability. Furthermore, the Pt/ZnO<sub>NMCAs</sub> exhibit a 3.5-fold improvement in response time, with a rise time of 9.6 s compared to 51.9 s for the DNC-based variant under a UV light intensity of 2.5 mW·cm<sup>-</sup>² in self-powered mode. These findings underscore the significant potential of NMCA-structured ZnO nanomaterials as high-performance candidates for photoconductive devices, advancing the development of self-powered optoelectronic technologies.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102754"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulation of signaling pathways by metal and metal-doped nanozymes in inflammatory bowel disease: A therapeutic perspective
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102747
Mydhili Govindarasu , Jomon George Joy , Garima Sharma , Jin-Chul Kim
{"title":"Regulation of signaling pathways by metal and metal-doped nanozymes in inflammatory bowel disease: A therapeutic perspective","authors":"Mydhili Govindarasu ,&nbsp;Jomon George Joy ,&nbsp;Garima Sharma ,&nbsp;Jin-Chul Kim","doi":"10.1016/j.nantod.2025.102747","DOIUrl":"10.1016/j.nantod.2025.102747","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic condition driven by oxidative stress and dysregulated immune responses. Key pathways like nuclear factor-kappa B (NF-κB) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) play pivotal roles in IBD pathogenesis. By altering these pathways, pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β are suppressed, lowering inflammation and re-establishing immunological balance. Novel treatments for IBD have been developed using metal-based nanozymes that are designed to replicate natural enzymatic processes. These nanozymes, including iron-doped, zinc-doped, ceria-doped, transition metal-doped, and noble metal-doped variants, exhibit robust catalytic activities, such as superoxide dismutase (SOD)-like, catalase (CAT)-like, and peroxidase (POD)-like functions. By scavenging reactive oxygen species (ROS) and restoring redox balance, they mitigate oxidative stress, a key driver of IBD progression. These nanozymes interact with important signaling pathways linked to IBD in addition to their enzymatic roles. They inhibit NF-κB signaling, reducing the release of pro-inflammatory cytokines, and regulate the JAK/STAT pathway to balance immunological responses. Their therapeutic potential is increased by this dual action, which concurrently addresses immunological dysregulation and oxidative stress. Metal-doped nanozymes are a promising substitute for conventional anti-inflammatory and immunosuppressive therapies due to their precise, targeted action. The review article explores the latest developments in metal based nanozyme research, their catalytic characteristics, and how they affect IBD treatment, as well as potential future paths for the area.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102747"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777028","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
Administration route-commended concise organ-selective mRNA transfection (ACCOST) by cyclic disulfide-primed short polyethylenimine
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102741
Ruonan Ye , Qiongzhe Ren , Limin Chang , Siqi Zhang , Changchang Deng , Li Cao , Meng Shi , Bo Lou , Fenghua Meng , Shi Du , Keyun Ren , Xijun Piao , Congcong Xu , Zhiyuan Zhong
{"title":"Administration route-commended concise organ-selective mRNA transfection (ACCOST) by cyclic disulfide-primed short polyethylenimine","authors":"Ruonan Ye ,&nbsp;Qiongzhe Ren ,&nbsp;Limin Chang ,&nbsp;Siqi Zhang ,&nbsp;Changchang Deng ,&nbsp;Li Cao ,&nbsp;Meng Shi ,&nbsp;Bo Lou ,&nbsp;Fenghua Meng ,&nbsp;Shi Du ,&nbsp;Keyun Ren ,&nbsp;Xijun Piao ,&nbsp;Congcong Xu ,&nbsp;Zhiyuan Zhong","doi":"10.1016/j.nantod.2025.102741","DOIUrl":"10.1016/j.nantod.2025.102741","url":null,"abstract":"<div><div>mRNA technology holds great promise for addressing a spectrum of diseases. Achieving widespread clinical utility of mRNA therapeutics requires effective transfection of mRNA to specific organs. Here we introduce a cyclic disulfide-primed short polyethyleneimine (CD-PEI) polymer that demonstrates administration route-commended concise organ-selective mRNA transfection (ACCOST) <em>in vivo</em>. The cyclic disulfide groups on the PEI polymer facilitate thiol-mediated cytosolic mRNA delivery and high transfection of different types of cells including hard-to-transfect immune cells. Remarkably, CD-PEI-mRNA complex achieves nearly 100 % organ-specific transfection in pancreas, lymph nodes, brain/spinal cord, and spleen <em>via</em> intraperitoneal, subcutaneous, intrathecal injection, and intravenous injections, respectively, with negligible accumulation in non-target organs. The intravenous injection to pregnant mice results in selective mRNA expression in the placenta instead. The spleen targeting occurs likely <em>via</em> erythrocyte-hijacking mechanism and systemically administered mRNA vaccines elicit robust antigen-specific anti-tumor immunity in murine B16-OVA model. Therefore, our ACCOST technology presents a novel strategy for organ-specific mRNA transfection.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102741"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777139","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
Visualizing the substrate-dependent structural evolution of Na2WO4 via in-situ transmission electron microscopy
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102751
Kunkun Wei , Yutao Ren , Yilin Zhao , Fangwei Liu , Xutao Chen , Yue Wang , Shihui Zou , Chengyuan Liu , Yang Pan , Jianguo Huang , Wentao Yuan , Zhongkang Han , Yong Wang , Jie Fan
{"title":"Visualizing the substrate-dependent structural evolution of Na2WO4 via in-situ transmission electron microscopy","authors":"Kunkun Wei ,&nbsp;Yutao Ren ,&nbsp;Yilin Zhao ,&nbsp;Fangwei Liu ,&nbsp;Xutao Chen ,&nbsp;Yue Wang ,&nbsp;Shihui Zou ,&nbsp;Chengyuan Liu ,&nbsp;Yang Pan ,&nbsp;Jianguo Huang ,&nbsp;Wentao Yuan ,&nbsp;Zhongkang Han ,&nbsp;Yong Wang ,&nbsp;Jie Fan","doi":"10.1016/j.nantod.2025.102751","DOIUrl":"10.1016/j.nantod.2025.102751","url":null,"abstract":"<div><div>Supported nanocatalysts often undergo sintering at elevated temperatures, whereas the dispersion of large particles into small particles is uncommon. Here, we discover that Na<sub>2</sub>WO<sub>4</sub> evolves from large bulk particles to evenly distributed high-concentration nanoclusters on the ZrO<sub>2</sub> surface but remains as large particles on the TiO<sub>2</sub> surface at high temperatures. This substrate-dependent structural evolution is visualized by in-situ transmission electron microscopy and rationalized by the differing interactions between Na<sub>2</sub>WO<sub>4</sub> and the substrates. The great potential of this substrate-dependent structural evolution in developing advanced Na<sub>2</sub>WO<sub>4</sub> cluster catalysts is demonstrated using methyl chloride-to-vinyl chloride as a probe reaction. Benefiting from the presence of high-concentration Na<sub>2</sub>WO<sub>4</sub> nanoclusters that effectively couple ·CH<sub>2</sub>Cl radicals, Na<sub>2</sub>WO<sub>4</sub>/ZrO<sub>2</sub> exhibits a C<sub>2</sub>H<sub>3</sub>Cl selectivity of 31.9 % and a yield of 20.0 % at 700 °C, which is much higher than those of Na<sub>2</sub>WO<sub>4</sub>/TiO<sub>2</sub>.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102751"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777030","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
A nuclei bombing nano-system improves STING-activated cancer immunotherapy
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102749
Shuai Guo , Tianwang Guan , Rundong Tai , Long Ma , Yushen Ke , Jujian Ye , Huiwan Chen , Yuxuan Pan , Xiaodong Ning , Xueqin Shi , Zhilin Deng , Yafang Xiao , Shaohui Deng , Peier Chen , Zhenhua Li , Xiaozhong Qiu , Kelong Fan , Zheyu Shen , Caiwen Ou
{"title":"A nuclei bombing nano-system improves STING-activated cancer immunotherapy","authors":"Shuai Guo ,&nbsp;Tianwang Guan ,&nbsp;Rundong Tai ,&nbsp;Long Ma ,&nbsp;Yushen Ke ,&nbsp;Jujian Ye ,&nbsp;Huiwan Chen ,&nbsp;Yuxuan Pan ,&nbsp;Xiaodong Ning ,&nbsp;Xueqin Shi ,&nbsp;Zhilin Deng ,&nbsp;Yafang Xiao ,&nbsp;Shaohui Deng ,&nbsp;Peier Chen ,&nbsp;Zhenhua Li ,&nbsp;Xiaozhong Qiu ,&nbsp;Kelong Fan ,&nbsp;Zheyu Shen ,&nbsp;Caiwen Ou","doi":"10.1016/j.nantod.2025.102749","DOIUrl":"10.1016/j.nantod.2025.102749","url":null,"abstract":"<div><div>The activation of the stimulator of interferon genes (STING) pathway presents a promising therapeutic strategy for pancreatic cancer by enhancing immune responses and reprogramming the immunosuppressive tumor microenvironment (TME). Ferroptosis, an iron-dependent form of cell death, can synergize with STING activation through reactive oxygen species (ROS)-induced DNA damage. However, its efficacy is hindered by poor vascularization, inefficient delivery of STING agonists, and tumor resistance mechanisms that suppress ROS levels. To overcome these limitations, we developed a \"nuclei bombing\" nano-system using extremely small cuprous oxide modified magneto-human heavy chain ferritin (ES-CO@M-HFn). This system targets pancreatic cancer cells overexpressing transferrin receptor 1 (TfR1) and releases Cu<sup>+</sup> and Fe<sup>3+</sup> ions in response to the acidic (pH 6.8) and glutathione (GSH)-rich TME. These ions form a Cu-Fe catalytic cycle under high H₂O₂ levels, continuously generating Fe<sup>2+</sup>, Cu<sup>+</sup>, and robust ROS, thereby inducing ferroptosis and cuproptosis. This creates a synergistic feedback loop that amplifies oxidative damage, leading to extensive DNA damage and tumor cell destruction—termed the \"nuclei bombing\" effect. The resulting DNA fragments activate the STING pathway, reprogramming the TME by maturing dendritic cells, repolarizing macrophages, and activating CD8<sup>+</sup> T cells. This comprehensive approach generates a potent immune response, significantly suppressing tumor growth and metastasis, and offers a transformative strategy for pancreatic cancer treatment.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102749"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777137","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
The peptide-Au clusters inhibit EGFR exon 19 deletion mutant non-small cell lung cancer
IF 13.2 1区 材料科学
Nano Today Pub Date : 2025-04-05 DOI: 10.1016/j.nantod.2025.102744
Wencong Zhao , Wendi Huo , Haoran Dang , Zhongying Du , Qing Yuan , Kai Cao , Xueyun Gao
{"title":"The peptide-Au clusters inhibit EGFR exon 19 deletion mutant non-small cell lung cancer","authors":"Wencong Zhao ,&nbsp;Wendi Huo ,&nbsp;Haoran Dang ,&nbsp;Zhongying Du ,&nbsp;Qing Yuan ,&nbsp;Kai Cao ,&nbsp;Xueyun Gao","doi":"10.1016/j.nantod.2025.102744","DOIUrl":"10.1016/j.nantod.2025.102744","url":null,"abstract":"<div><div>Epidermal growth factor receptor (EGFR) exon 19 deletions are a common mutation that can lead to non-small cell lung cancer (NSCLC). Here, we designed and synthesized Au clusters coated with EGFR-target peptides to treat EGFR exon 19 deletions mutated NSCLC. Two sequences of peptides (namely P1 and P2 peptide) were designed for synthesis two Au clusters (namely P1-Au and P2-Au), respectively. These two clusters specifically target the extracellular region of EGFR and enter cancer cells through endocytosis. ICP-MS measurements, enzyme activity experiments and cytotoxicity studies in H1650 cells (exon 19 deletions of EGFR) demonstrated that P1-Au clusters have stronger targeting ability towards EGFR, well inhibits EGFR phosphorylation and outcome a better anti-tumor effect than that of P2-Au clusters. Further experiments revealed that the P1-Au clusters enter H1650 cells through the clathrin-mediated endocytosis pathway, escape from lysosomes to the cytoplasm, and inhibit the phosphorylation of EGFR exon 19 deletions and its downstream protein to induce cancer cell apoptosis. P1-Au clusters significantly inhibited the tumor growth in an H1650 xenograft model via suppress EGFR exon 19 deletions mutant activation.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"63 ","pages":"Article 102744"},"PeriodicalIF":13.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777130","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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