Pub Date : 2024-09-26DOI: 10.1038/s41565-024-01783-2
Xianguang Ding, JingJing Zhang, Shuangshuang Wan, Xu Wang, Zhiyu Wang, Kefeng Pu, Mao Wang, Yi Cao, Lixing Weng, Houjuan Zhu, Fei Peng, Jie Chao, Renjun Pei, David Tai Leong, Lianhui Wang
The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles’ elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.
个性化癌症免疫疗法的成功取决于树突状细胞和巨噬细胞最初的肿瘤抗原呈递。肿瘤衍生的细胞外囊泡(TEV)含有丰富的肿瘤抗原分子。然而,TEVs 表面存在的抗吞噬信号(如分化簇 47(CD47))会导致树突状细胞和巨噬细胞逃避相同的抗吞噬信号。在这里,我们展示了氧化铁氢氧化物纳米复合材料可以成功地掩盖 TEV 表面,并在不影响细胞外囊泡诱导免疫目标的情况下解除吞噬作用。内化后,掩膜在溶酶体中分解,释放出肿瘤抗原货物。在动物模型和人类恶性胸腔积液临床样本中,这能触发抗原呈递,促进树突状细胞活化和成熟以及巨噬细胞重编程,从而大幅减少肿瘤体积和转移。这种直接的掩蔽策略消除了临床样本中无处不在的抗吞噬阻滞,可普遍应用于所有患者特异性 TEV,作为增强免疫疗法的肿瘤抗原制剂。
{"title":"Non-discriminating engineered masking of immuno-evasive ligands on tumour-derived extracellular vesicles enhances tumour vaccination outcomes","authors":"Xianguang Ding, JingJing Zhang, Shuangshuang Wan, Xu Wang, Zhiyu Wang, Kefeng Pu, Mao Wang, Yi Cao, Lixing Weng, Houjuan Zhu, Fei Peng, Jie Chao, Renjun Pei, David Tai Leong, Lianhui Wang","doi":"10.1038/s41565-024-01783-2","DOIUrl":"https://doi.org/10.1038/s41565-024-01783-2","url":null,"abstract":"<p>The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles’ elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.</p>","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"36 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321211","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}
Pub Date : 2024-09-26DOI: 10.1038/s41565-024-01793-0
Kai Wu, Zhengli Dou, Shibo Deng, Die Wu, Bin Zhang, Haobo Yang, Runlai Li, Chuxin Lei, Yongzheng Zhang, Qiang Fu, Guihua Yu
Electronic systems and devices operating at significant power levels demand sophisticated solutions for heat dissipation. Although materials with high thermal conductivity hold promise for exceptional thermal transport across nano- and microscale interfaces under ideal conditions, their performance often falls short by several orders of magnitude in the complex thermal interfaces typical of real-world applications. This study introduces mechanochemistry-mediated colloidal liquid metals composed of Galinstan and aluminium nitride to bridge the practice–theory disparity. These colloids demonstrate thermal resistances of between 0.42 and 0.86 mm2 K W−1 within actual thermal interfaces, outperforming leading thermal conductors by over an order of magnitude. This superior performance is attributed to the gradient heterointerface with efficient thermal transport across liquid–solid interfaces and the notable colloidal thixotropy. In practical devices, experimental results demonstrate their capacity to extract 2,760 W of heat from a 16 cm2 thermal source when coupled with microchannel cooling, and can facilitate a 65% reduction in pump electricity consumption. This advancement in thermal interface technology offers a promising solution for efficient and sustainable cooling of devices operating at kilowatt levels.
在高功率水平下运行的电子系统和设备需要复杂的散热解决方案。虽然在理想条件下,高热导率材料有望在纳米和微米级界面上实现卓越的热传输,但在实际应用中典型的复杂热界面上,它们的性能往往相差几个数量级。本研究介绍了由 Galinstan 和氮化铝组成的机械化学介导的胶体液态金属,以弥合实践与理论之间的差距。这些胶体在实际热界面中的热阻介于 0.42 和 0.86 mm2 K W-1 之间,比主要热导体的热阻高出一个数量级以上。这种优异的性能归功于梯度异质界面在液固界面上的高效热传输以及胶体显著的触变性。在实际设备中,实验结果表明,当与微通道冷却相结合时,它们能从 16 平方厘米的热源中提取 2,760 W 的热量,并能将泵的耗电量降低 65%。热界面技术的这一进步为千瓦级设备的高效和可持续冷却提供了一个前景广阔的解决方案。
{"title":"Mechanochemistry-mediated colloidal liquid metals for electronic device cooling at kilowatt levels","authors":"Kai Wu, Zhengli Dou, Shibo Deng, Die Wu, Bin Zhang, Haobo Yang, Runlai Li, Chuxin Lei, Yongzheng Zhang, Qiang Fu, Guihua Yu","doi":"10.1038/s41565-024-01793-0","DOIUrl":"https://doi.org/10.1038/s41565-024-01793-0","url":null,"abstract":"<p>Electronic systems and devices operating at significant power levels demand sophisticated solutions for heat dissipation. Although materials with high thermal conductivity hold promise for exceptional thermal transport across nano- and microscale interfaces under ideal conditions, their performance often falls short by several orders of magnitude in the complex thermal interfaces typical of real-world applications. This study introduces mechanochemistry-mediated colloidal liquid metals composed of Galinstan and aluminium nitride to bridge the practice–theory disparity. These colloids demonstrate thermal resistances of between 0.42 and 0.86 mm<sup>2</sup> K W<sup>−1</sup> within actual thermal interfaces, outperforming leading thermal conductors by over an order of magnitude. This superior performance is attributed to the gradient heterointerface with efficient thermal transport across liquid–solid interfaces and the notable colloidal thixotropy. In practical devices, experimental results demonstrate their capacity to extract 2,760 W of heat from a 16 cm<sup>2</sup> thermal source when coupled with microchannel cooling, and can facilitate a 65% reduction in pump electricity consumption. This advancement in thermal interface technology offers a promising solution for efficient and sustainable cooling of devices operating at kilowatt levels.</p>","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"57 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321213","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}
Pub Date : 2024-09-26DOI: 10.1038/s41565-024-01788-x
Eva Díaz, Alberto Anadón, Pablo Olleros-Rodríguez, Harjinder Singh, Héloïse Damas, Paolo Perna, Martina Morassi, Aristide Lemaître, Michel Hehn, Jon Gorchon
Electrical current pulses can be used to manipulate magnetization efficiently via spin–orbit torques. Pulse durations as short as a few picoseconds have been used to switch the magnetization of ferromagnetic films, reaching the terahertz regime. However, little is known about the reversal mechanisms and energy requirements in the ultrafast switching regime. In this work we quantify the energy cost for magnetization reversal over seven orders of magnitude in pulse duration, in both ferromagnetic and ferrimagnetic samples, bridging quasi-static spintronics and femtomagnetism. To this end, we develop a method to stretch picosecond pulses generated by a photoconductive switch by an order of magnitude. Thereby we can create current pulses from picoseconds to durations approaching the pulse width available with commercial instruments. We show that the energy cost for spin–orbit torque switching decreases by more than an order of magnitude in all samples when the pulse duration enters the picosecond range. We project an energy cost of 9 fJ for a 100 × 100 nm2 ferrimagnetic device. Micromagnetic and macrospin simulations unveil a transition from a non-coherent to a coherent magnetization reversal with a strong modification of the magnetization dynamical trajectories as pulse duration is reduced. Our results show the potential for high-speed magnetic spin–orbit torque memories and highlight alternative magnetization reversal pathways at fast timescales.
{"title":"Energy-efficient picosecond spin–orbit torque magnetization switching in ferro- and ferrimagnetic films","authors":"Eva Díaz, Alberto Anadón, Pablo Olleros-Rodríguez, Harjinder Singh, Héloïse Damas, Paolo Perna, Martina Morassi, Aristide Lemaître, Michel Hehn, Jon Gorchon","doi":"10.1038/s41565-024-01788-x","DOIUrl":"https://doi.org/10.1038/s41565-024-01788-x","url":null,"abstract":"<p>Electrical current pulses can be used to manipulate magnetization efficiently via spin–orbit torques. Pulse durations as short as a few picoseconds have been used to switch the magnetization of ferromagnetic films, reaching the terahertz regime. However, little is known about the reversal mechanisms and energy requirements in the ultrafast switching regime. In this work we quantify the energy cost for magnetization reversal over seven orders of magnitude in pulse duration, in both ferromagnetic and ferrimagnetic samples, bridging quasi-static spintronics and femtomagnetism. To this end, we develop a method to stretch picosecond pulses generated by a photoconductive switch by an order of magnitude. Thereby we can create current pulses from picoseconds to durations approaching the pulse width available with commercial instruments. We show that the energy cost for spin–orbit torque switching decreases by more than an order of magnitude in all samples when the pulse duration enters the picosecond range. We project an energy cost of 9 fJ for a 100 × 100 nm<sup>2</sup> ferrimagnetic device. Micromagnetic and macrospin simulations unveil a transition from a non-coherent to a coherent magnetization reversal with a strong modification of the magnetization dynamical trajectories as pulse duration is reduced. Our results show the potential for high-speed magnetic spin–orbit torque memories and highlight alternative magnetization reversal pathways at fast timescales.</p>","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"24 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321212","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}
Pub Date : 2024-09-26DOI: 10.1038/s41565-024-01776-1
Harry Mönig
A complex experiment based on atomic force microscopy provides the quantitative energy-level diagram of a single molecule.
基于原子力显微镜的复杂实验提供了单个分子的定量能级图。
{"title":"Playing electron ping-pong with the excited states of a single molecule","authors":"Harry Mönig","doi":"10.1038/s41565-024-01776-1","DOIUrl":"https://doi.org/10.1038/s41565-024-01776-1","url":null,"abstract":"A complex experiment based on atomic force microscopy provides the quantitative energy-level diagram of a single molecule.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"203 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321209","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}
Pub Date : 2024-09-23DOI: 10.1038/s41565-024-01781-4
Enbo Zhu, Jiaji Yu, Yan-Ruide Li, Feiyang Ma, Yu-Chen Wang, Yang Liu, Miao Li, Yu Jeong Kim, Yichen Zhu, Zoe Hahn, Yang Zhou, James Brown, Yuchong Zhang, Matteo Pelegrini, Tzung Hsiai, Lili Yang, Yu Huang
Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation. Current CAR T cell manufacturing falls short of mimicking immunological synapses. A new graphene oxide antigen-presenting platform (GO-APP) addresses this issue, improving CAR T cell production while eliminating the need for interleukin-2 supplementation.
嵌合抗原受体(CAR)工程 T 细胞是治疗癌症的一线疗法。然而,目前的 CAR T 细胞制造方案无法充分再现免疫突触的形成。针对这一限制,我们开发了一种灵活的氧化石墨烯抗原递呈平台(GO-APP),可将抗体锚定在氧化石墨烯上。通过在氧化石墨烯(GO-APP3/28)上装饰抗 CD3(αCD3)和抗 CD28(αCD28),我们实现了显著的 T 细胞增殖。GO-APP3/28 与 T 细胞之间的体外相互作用密切模拟了体内抗原递呈细胞与 T 细胞之间的免疫突触。这种免疫突触模拟显示了刺激 T 细胞增殖的强大能力,同时保留了 T 细胞的多功能性和高效力。同时,它还提高了 CAR 基因工程的效率,与标准方案相比,CAR T 细胞的产量增加了五倍以上。值得注意的是,GO-APP3/28 能刺激 T 细胞产生适当的自分泌白细胞介素-2(IL-2),克服了体外培养对外部 IL-2 补充的依赖,为不依赖 IL-2 补充培养基于 T 细胞的产品提供了机会。
{"title":"Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies","authors":"Enbo Zhu, Jiaji Yu, Yan-Ruide Li, Feiyang Ma, Yu-Chen Wang, Yang Liu, Miao Li, Yu Jeong Kim, Yichen Zhu, Zoe Hahn, Yang Zhou, James Brown, Yuchong Zhang, Matteo Pelegrini, Tzung Hsiai, Lili Yang, Yu Huang","doi":"10.1038/s41565-024-01781-4","DOIUrl":"10.1038/s41565-024-01781-4","url":null,"abstract":"Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation. Current CAR T cell manufacturing falls short of mimicking immunological synapses. A new graphene oxide antigen-presenting platform (GO-APP) addresses this issue, improving CAR T cell production while eliminating the need for interleukin-2 supplementation.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1914-1922"},"PeriodicalIF":38.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276996","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}
Pub Date : 2024-09-19DOI: 10.1038/s41565-024-01782-3
A customized Ti-Nano resin is used to fabricate 3D photonic crystals with a complete bandgap in the visible spectrum through a nanoscale printing technique. The 3D printed and annealed titania photonic crystals show perfect reflectance within the wavelength range associated with this bandgap.
{"title":"3D printed photonic crystals with a complete bandgap in the visible range","authors":"","doi":"10.1038/s41565-024-01782-3","DOIUrl":"10.1038/s41565-024-01782-3","url":null,"abstract":"A customized Ti-Nano resin is used to fabricate 3D photonic crystals with a complete bandgap in the visible spectrum through a nanoscale printing technique. The 3D printed and annealed titania photonic crystals show perfect reflectance within the wavelength range associated with this bandgap.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1767-1768"},"PeriodicalIF":38.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245316","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}
Pub Date : 2024-09-19DOI: 10.1038/s41565-024-01785-0
Yan Zhuo, Zhen Luo, Zhu Zhu, Jie Wang, Xiang Li, Zhuan Zhang, Cong Guo, Bingqi Wang, Di Nie, Yong Gan, Guoqing Hu, Miaorong Yu
Efficient cytosolic delivery is a significant hurdle when using short interfering RNA (siRNA) in therapeutic applications. Here we show that cholesterol-rich exosomes are prone to entering cancer cells through membrane fusion, achieving direct cytosolic delivery of siRNA. Molecular dynamics simulations suggest that deformation and increased contact with the target cell membrane facilitate membrane fusion. In vitro we show that cholesterol-enriched milk-derived exosomes (MEs) achieve a significantly higher gene silencing effect of siRNA, inducing superior cancer cell apoptosis compared with the native and cholesterol-depleted MEs, as well as conventional transfection agents. When administered orally or intravenously to mice bearing orthotopic or subcutaneous tumours, the cholesterol-enriched MEs/siRNA exhibit antitumour activity superior to that of lipid nanoparticles. Collectively, by modulating the cholesterol content of exosome membranes to facilitate cell entry via membrane fusion, we provide a promising approach for siRNA-based gene therapy, paving the way for effective, safe and simple gene therapy strategies. Researchers demonstrate that cholesterol-enriched exosomes can deliver siRNA directly into cancer cells, bypassing normal cellular barriers and significantly enhancing gene silencing. This offers a more effective method for gene therapy applications.
{"title":"Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes","authors":"Yan Zhuo, Zhen Luo, Zhu Zhu, Jie Wang, Xiang Li, Zhuan Zhang, Cong Guo, Bingqi Wang, Di Nie, Yong Gan, Guoqing Hu, Miaorong Yu","doi":"10.1038/s41565-024-01785-0","DOIUrl":"10.1038/s41565-024-01785-0","url":null,"abstract":"Efficient cytosolic delivery is a significant hurdle when using short interfering RNA (siRNA) in therapeutic applications. Here we show that cholesterol-rich exosomes are prone to entering cancer cells through membrane fusion, achieving direct cytosolic delivery of siRNA. Molecular dynamics simulations suggest that deformation and increased contact with the target cell membrane facilitate membrane fusion. In vitro we show that cholesterol-enriched milk-derived exosomes (MEs) achieve a significantly higher gene silencing effect of siRNA, inducing superior cancer cell apoptosis compared with the native and cholesterol-depleted MEs, as well as conventional transfection agents. When administered orally or intravenously to mice bearing orthotopic or subcutaneous tumours, the cholesterol-enriched MEs/siRNA exhibit antitumour activity superior to that of lipid nanoparticles. Collectively, by modulating the cholesterol content of exosome membranes to facilitate cell entry via membrane fusion, we provide a promising approach for siRNA-based gene therapy, paving the way for effective, safe and simple gene therapy strategies. Researchers demonstrate that cholesterol-enriched exosomes can deliver siRNA directly into cancer cells, bypassing normal cellular barriers and significantly enhancing gene silencing. This offers a more effective method for gene therapy applications.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1858-1868"},"PeriodicalIF":38.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245352","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}
Residual tumours that persist after radiotherapy often develop acquired radiation resistance, increasing the risk of recurrence and metastasis while providing obstacles to re-irradiation. Using samples from patients and experimental mice, we discovered that FDX1 and LIAS, key regulators of cuproptosis, were up-regulated in residual tumours following radiotherapy, conferring the increased sensitivity to cuproptosis. Therefore, we proposed a novel radiosensitization strategy focused on cuproptosis, using a copper-containing nanocapsule-like polyoxometalate as a paradigm. In an initial demonstration, we showed that the nanocapsule released copper ions in a controlled manner upon exposure to ionizing radiation. Furthermore, radiation-triggered cuproptosis overcame acquired radiation resistance even at clinically relevant radiation doses and activated a robust abscopal effect, with a 40% cure rate in both radioresistant and re-irradiation tumour models. Collectively, targeting cuproptosis is a compelling strategy for addressing acquired radiation resistance, optimizing the local antitumour effects of radiotherapy while simultaneously activating systemic antitumour immunity. Acquired radiation resistance in residual tumours impedes the therapeutic outcome of re-irradiation. This study reports a novel radiosensitization strategy that targets cuproptosis to overcome resistance and enhance antitumour effects.
{"title":"A cuproptosis nanocapsule for cancer radiotherapy","authors":"You Liao, Dongmei Wang, Chenglu Gu, Xue Wang, Shuang Zhu, Ziye Zheng, Fuquan Zhang, Junfang Yan, Zhanjun Gu","doi":"10.1038/s41565-024-01784-1","DOIUrl":"10.1038/s41565-024-01784-1","url":null,"abstract":"Residual tumours that persist after radiotherapy often develop acquired radiation resistance, increasing the risk of recurrence and metastasis while providing obstacles to re-irradiation. Using samples from patients and experimental mice, we discovered that FDX1 and LIAS, key regulators of cuproptosis, were up-regulated in residual tumours following radiotherapy, conferring the increased sensitivity to cuproptosis. Therefore, we proposed a novel radiosensitization strategy focused on cuproptosis, using a copper-containing nanocapsule-like polyoxometalate as a paradigm. In an initial demonstration, we showed that the nanocapsule released copper ions in a controlled manner upon exposure to ionizing radiation. Furthermore, radiation-triggered cuproptosis overcame acquired radiation resistance even at clinically relevant radiation doses and activated a robust abscopal effect, with a 40% cure rate in both radioresistant and re-irradiation tumour models. Collectively, targeting cuproptosis is a compelling strategy for addressing acquired radiation resistance, optimizing the local antitumour effects of radiotherapy while simultaneously activating systemic antitumour immunity. Acquired radiation resistance in residual tumours impedes the therapeutic outcome of re-irradiation. This study reports a novel radiosensitization strategy that targets cuproptosis to overcome resistance and enhance antitumour effects.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1892-1902"},"PeriodicalIF":38.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245355","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}
Pub Date : 2024-09-19DOI: 10.1038/s41565-024-01787-y
Han-Ming Hau, Tara Mishra, Colin Ophus, Tzu-Yang Huang, Karen Bustilo, Yingzhi Sun, Xiaochen Yang, Tucker Holstun, Xinye Zhao, Shilong Wang, Yang Ha, Gi-Hyeok Lee, Chengyu Song, John Turner, Jianming Bai, Lu Ma, Ke Chen, Feng Wang, Wanli Yang, Bryan D. McCloskey, Zijian Cai, Gerbrand Ceder
Manganese-based materials have tremendous potential to become the next-generation lithium-ion cathode as they are Earth abundant, low cost and stable. Here we show how the mobility of manganese cations can be used to obtain a unique nanosized microstructure in large-particle-sized cathode materials with enhanced electrochemical properties. By combining atomic-resolution scanning transmission electron microscopy, four-dimensional scanning electron nanodiffraction and in situ X-ray diffraction, we show that when a partially delithiated, high-manganese-content, disordered rocksalt cathode is slightly heated, it forms a nanomosaic of partially ordered spinel domains of 3–7 nm in size, which impinge on each other at antiphase boundaries. The short coherence length of these domains removes the detrimental two-phase lithiation reaction present near 3 V in a regular spinel and turns it into a solid solution. This nanodomain structure enables good rate performance and delivers 200 mAh g−1 discharge capacity in a (partially) disordered material with an average primary particle size of ∼5 µm. The work not only expands the synthesis strategies available for developing high-performance Earth-abundant manganese-based cathodes but also offers structural insights into the ability to nanoengineer spinel-like phases. By inducing a transformation in a manganese-rich cation-disordered rocksalt, partially ordered spinels with nanomosaic domains of 3–7 nm in size can be obtained, which exhibit high energy density and rate capability at an average particle size of 3–5 µm.
锰基材料具有丰富的地球资源、低成本和稳定性,因此具有成为下一代锂离子正极材料的巨大潜力。在这里,我们展示了如何利用锰阳离子的流动性在大颗粒阴极材料中获得独特的纳米微结构,从而增强电化学性能。通过结合原子分辨率扫描透射电子显微镜、四维扫描电子纳米衍射和原位 X 射线衍射,我们展示了当部分脱锰的高锰含量无序岩盐阴极受到轻微加热时,会形成 3-7 纳米大小的部分有序尖晶石畴的纳米马赛克,这些畴在反相边界相互撞击。这些畴的相干长度很短,消除了规则尖晶石在 3 V 附近出现的有害的两相石化反应,并将其转化为固溶体。这种纳米畴结构实现了良好的速率性能,并在平均主颗粒尺寸为 5 µm 的(部分)无序材料中提供了 200 mAh g-1 的放电容量。这项研究不仅拓展了开发高性能富地锰基阴极的合成策略,还从结构上深入了解了纳米工程尖晶石相的能力。
{"title":"Earth-abundant Li-ion cathode materials with nanoengineered microstructures","authors":"Han-Ming Hau, Tara Mishra, Colin Ophus, Tzu-Yang Huang, Karen Bustilo, Yingzhi Sun, Xiaochen Yang, Tucker Holstun, Xinye Zhao, Shilong Wang, Yang Ha, Gi-Hyeok Lee, Chengyu Song, John Turner, Jianming Bai, Lu Ma, Ke Chen, Feng Wang, Wanli Yang, Bryan D. McCloskey, Zijian Cai, Gerbrand Ceder","doi":"10.1038/s41565-024-01787-y","DOIUrl":"10.1038/s41565-024-01787-y","url":null,"abstract":"Manganese-based materials have tremendous potential to become the next-generation lithium-ion cathode as they are Earth abundant, low cost and stable. Here we show how the mobility of manganese cations can be used to obtain a unique nanosized microstructure in large-particle-sized cathode materials with enhanced electrochemical properties. By combining atomic-resolution scanning transmission electron microscopy, four-dimensional scanning electron nanodiffraction and in situ X-ray diffraction, we show that when a partially delithiated, high-manganese-content, disordered rocksalt cathode is slightly heated, it forms a nanomosaic of partially ordered spinel domains of 3–7 nm in size, which impinge on each other at antiphase boundaries. The short coherence length of these domains removes the detrimental two-phase lithiation reaction present near 3 V in a regular spinel and turns it into a solid solution. This nanodomain structure enables good rate performance and delivers 200 mAh g−1 discharge capacity in a (partially) disordered material with an average primary particle size of ∼5 µm. The work not only expands the synthesis strategies available for developing high-performance Earth-abundant manganese-based cathodes but also offers structural insights into the ability to nanoengineer spinel-like phases. By inducing a transformation in a manganese-rich cation-disordered rocksalt, partially ordered spinels with nanomosaic domains of 3–7 nm in size can be obtained, which exhibit high energy density and rate capability at an average particle size of 3–5 µm.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1831-1839"},"PeriodicalIF":38.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01787-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245319","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}