Pub Date : 2024-10-01DOI: 10.1038/s41565-024-01747-6
Lulu Xue, Gan Zhao, Ningqiang Gong, Xuexiang Han, Sarah J. Shepherd, Xinhong Xiong, Zebin Xiao, Rohan Palanki, Junchao Xu, Kelsey L. Swingle, Claude C. Warzecha, Rakan El-Mayta, Vivek Chowdhary, Il-Chul Yoon, Jingcheng Xu, Jiaxi Cui, Yi Shi, Mohamad-Gabriel Alameh, Karin Wang, Lili Wang, Darrin J. Pochan, Drew Weissman, Andrew E. Vaughan, James M. Wilson, Michael J. Mitchell
Systemic delivery of messenger RNA (mRNA) for tissue-specific targeting using lipid nanoparticles (LNPs) holds great therapeutic potential. Nevertheless, how the structural characteristics of ionizable lipids (lipidoids) impact their capability to target cells and organs remains unclear. Here we engineered a class of siloxane-based ionizable lipids with varying structures and formulated siloxane-incorporated LNPs (SiLNPs) to control in vivo mRNA delivery to the liver, lung and spleen in mice. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy. Using organ-specific SiLNPs to deliver gene editing machinery, we achieve robust gene knockout in the liver of wild-type mice and in the lungs of both transgenic GFP and Lewis lung carcinoma (LLC) tumour-bearing mice. Moreover, we showed effective recovery from viral infection-induced lung damage by delivering angiogenic factors with lung-targeted Si5-N14 LNPs. We envision that our SiLNPs will aid in the clinical translation of mRNA therapeutics for next-generation tissue-specific protein replacement therapies, regenerative medicine and gene editing. mRNA delivery through LNPs targeting specific organs holds great clinical potential, but it remains unclear how the structure of the lipidoids in the LNPs controls organ tropism. Here the authors direct in vivo delivery of siloxane-based LNPs via structural alteration of the ionizable structure of the constituting lipidoids.
{"title":"Combinatorial design of siloxane-incorporated lipid nanoparticles augments intracellular processing for tissue-specific mRNA therapeutic delivery","authors":"Lulu Xue, Gan Zhao, Ningqiang Gong, Xuexiang Han, Sarah J. Shepherd, Xinhong Xiong, Zebin Xiao, Rohan Palanki, Junchao Xu, Kelsey L. Swingle, Claude C. Warzecha, Rakan El-Mayta, Vivek Chowdhary, Il-Chul Yoon, Jingcheng Xu, Jiaxi Cui, Yi Shi, Mohamad-Gabriel Alameh, Karin Wang, Lili Wang, Darrin J. Pochan, Drew Weissman, Andrew E. Vaughan, James M. Wilson, Michael J. Mitchell","doi":"10.1038/s41565-024-01747-6","DOIUrl":"10.1038/s41565-024-01747-6","url":null,"abstract":"Systemic delivery of messenger RNA (mRNA) for tissue-specific targeting using lipid nanoparticles (LNPs) holds great therapeutic potential. Nevertheless, how the structural characteristics of ionizable lipids (lipidoids) impact their capability to target cells and organs remains unclear. Here we engineered a class of siloxane-based ionizable lipids with varying structures and formulated siloxane-incorporated LNPs (SiLNPs) to control in vivo mRNA delivery to the liver, lung and spleen in mice. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy. Using organ-specific SiLNPs to deliver gene editing machinery, we achieve robust gene knockout in the liver of wild-type mice and in the lungs of both transgenic GFP and Lewis lung carcinoma (LLC) tumour-bearing mice. Moreover, we showed effective recovery from viral infection-induced lung damage by delivering angiogenic factors with lung-targeted Si5-N14 LNPs. We envision that our SiLNPs will aid in the clinical translation of mRNA therapeutics for next-generation tissue-specific protein replacement therapies, regenerative medicine and gene editing. mRNA delivery through LNPs targeting specific organs holds great clinical potential, but it remains unclear how the structure of the lipidoids in the LNPs controls organ tropism. Here the authors direct in vivo delivery of siloxane-based LNPs via structural alteration of the ionizable structure of the constituting lipidoids.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"132-143"},"PeriodicalIF":38.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330380","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/s41565-024-01792-1
Marti Checa, Bharat Pant, Alexander Puretzky, Bogdan Dryzhakov, Rama K. Vasudevan, Yongtao Liu, Pravin Kavle, Arvind Dasgupta, Lane W. Martin, Ye Cao, Liam Collins, Stephen Jesse, Neus Domingo, Kyle P. Kelley
Hierarchical assemblies of ferroelectric nanodomains, so-called super-domains, can exhibit exotic morphologies that lead to distinct behaviours. Controlling these super-domains reliably is critical for realizing states with desired functional properties. Here we reveal the super-switching mechanism by using a biased atomic force microscopy tip, that is, the switching of the in-plane super-domains, of a model ferroelectric Pb0.6Sr0.4TiO3. We demonstrate that the writing process is dominated by a super-domain nucleation and stabilization process. A complex scanning-probe trajectory enables on-demand formation of intricate centre-divergent, centre-convergent and flux-closure polar structures. Correlative piezoresponse force microscopy and optical spectroscopy confirm the topological nature and tunability of the emergent structures. The precise and versatile nanolithography in a ferroic material and the stability of the generated structures, also validated by phase-field modelling, suggests potential for reliable multi-state nanodevice architectures and, thereby, an alternative route for the creation of tunable topological structures for applications in neuromorphic circuits. A biased atomic force microscopy tip can write complex in-plane polar topologies in a model ferroelectric Pb0.6Sr0.4TiO3 by means of a smart scan path design. Hence, on-demand generation, reading and erasing of tunable topologies is possible.
{"title":"On-demand nanoengineering of in-plane ferroelectric topologies","authors":"Marti Checa, Bharat Pant, Alexander Puretzky, Bogdan Dryzhakov, Rama K. Vasudevan, Yongtao Liu, Pravin Kavle, Arvind Dasgupta, Lane W. Martin, Ye Cao, Liam Collins, Stephen Jesse, Neus Domingo, Kyle P. Kelley","doi":"10.1038/s41565-024-01792-1","DOIUrl":"10.1038/s41565-024-01792-1","url":null,"abstract":"Hierarchical assemblies of ferroelectric nanodomains, so-called super-domains, can exhibit exotic morphologies that lead to distinct behaviours. Controlling these super-domains reliably is critical for realizing states with desired functional properties. Here we reveal the super-switching mechanism by using a biased atomic force microscopy tip, that is, the switching of the in-plane super-domains, of a model ferroelectric Pb0.6Sr0.4TiO3. We demonstrate that the writing process is dominated by a super-domain nucleation and stabilization process. A complex scanning-probe trajectory enables on-demand formation of intricate centre-divergent, centre-convergent and flux-closure polar structures. Correlative piezoresponse force microscopy and optical spectroscopy confirm the topological nature and tunability of the emergent structures. The precise and versatile nanolithography in a ferroic material and the stability of the generated structures, also validated by phase-field modelling, suggests potential for reliable multi-state nanodevice architectures and, thereby, an alternative route for the creation of tunable topological structures for applications in neuromorphic circuits. A biased atomic force microscopy tip can write complex in-plane polar topologies in a model ferroelectric Pb0.6Sr0.4TiO3 by means of a smart scan path design. Hence, on-demand generation, reading and erasing of tunable topologies is possible.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"43-50"},"PeriodicalIF":38.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01792-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321210","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}
Pub Date : 2024-09-26DOI: 10.1038/s41565-024-01791-2
Lisanne Sellies, Jakob Eckrich, Leo Gross, Andrea Donarini, Jascha Repp
An increasing number of scanning-probe-based spectroscopic techniques provides access to diverse electronic properties of single molecules. Typically, these experiments can only study a subset of all electronic transitions, which obscures the unambiguous assignment of measured quantities to specific quantum transitions. Here we develop a single-molecule spectroscopy that enables the access to many quantum transitions of different types, including radiative, non-radiative and redox, that is, charge-related, transitions. Our method relies on controlled alternating single-charge attachment and detachment. For read-out, the spin states are mapped to charge states, which we can detect by atomic force microscopy. We can determine the relative energies of ground and excited states of an individual molecule and can prepare the molecule in defined excited states. After a proof-of-principle demonstration of the technique on pentacene, we apply it to PTCDA, the scanning-probe luminescence of which has been interpreted controversially. The method may be used to guide, understand and engineer tip-induced chemical reactions as well as phosphorescence and fluorescence of individual molecules. A sophisticated atomic force microscopy experiment enables a time-resolved tunnelling spectroscopy method that provides access to excited states of singles molecules. It quantifies the transition energies and can prepare a molecule in a specific excited state.
{"title":"Controlled single-electron transfer enables time-resolved excited-state spectroscopy of individual molecules","authors":"Lisanne Sellies, Jakob Eckrich, Leo Gross, Andrea Donarini, Jascha Repp","doi":"10.1038/s41565-024-01791-2","DOIUrl":"10.1038/s41565-024-01791-2","url":null,"abstract":"An increasing number of scanning-probe-based spectroscopic techniques provides access to diverse electronic properties of single molecules. Typically, these experiments can only study a subset of all electronic transitions, which obscures the unambiguous assignment of measured quantities to specific quantum transitions. Here we develop a single-molecule spectroscopy that enables the access to many quantum transitions of different types, including radiative, non-radiative and redox, that is, charge-related, transitions. Our method relies on controlled alternating single-charge attachment and detachment. For read-out, the spin states are mapped to charge states, which we can detect by atomic force microscopy. We can determine the relative energies of ground and excited states of an individual molecule and can prepare the molecule in defined excited states. After a proof-of-principle demonstration of the technique on pentacene, we apply it to PTCDA, the scanning-probe luminescence of which has been interpreted controversially. The method may be used to guide, understand and engineer tip-induced chemical reactions as well as phosphorescence and fluorescence of individual molecules. A sophisticated atomic force microscopy experiment enables a time-resolved tunnelling spectroscopy method that provides access to excited states of singles molecules. It quantifies the transition energies and can prepare a molecule in a specific excited state.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"27-35"},"PeriodicalIF":38.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01791-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321214","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}
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. Nano-masking of the surface of tumour-derived extracellular vesicles blocks their immune-evasive action. This improves their phagocytosis by dendritic cells, leading to maturation of T-cell action and culminating in undampened anti-tumour immunity.
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":"10.1038/s41565-024-01783-2","url":null,"abstract":"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. Nano-masking of the surface of tumour-derived extracellular vesicles blocks their immune-evasive action. This improves their phagocytosis by dendritic cells, leading to maturation of T-cell action and culminating in undampened anti-tumour immunity.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"156-166"},"PeriodicalIF":38.1,"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. This study introduces mechanochemistry-mediated colloidal liquid metals to enhance interface thermal transport in scalable electronic systems, offering an efficient cooling solution for thermal management in 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":"10.1038/s41565-024-01793-0","url":null,"abstract":"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. This study introduces mechanochemistry-mediated colloidal liquid metals to enhance interface thermal transport in scalable electronic systems, offering an efficient cooling solution for thermal management in devices operating at kilowatt levels.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"104-111"},"PeriodicalIF":38.1,"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. Experiments on spin–orbit torque magnetization switching over seven orders of magnitude in current pulse duration unveil a transition from non-coherent to coherent magnetization reversal as pulse duration is reduced and a reduction of energy consumption in the picosecond regime by an order of magnitude.
{"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":"10.1038/s41565-024-01788-x","url":null,"abstract":"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. Experiments on spin–orbit torque magnetization switching over seven orders of magnitude in current pulse duration unveil a transition from non-coherent to coherent magnetization reversal as pulse duration is reduced and a reduction of energy consumption in the picosecond regime by an order of magnitude.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"36-42"},"PeriodicalIF":38.1,"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":"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":"20 1","pages":"6-7"},"PeriodicalIF":38.1,"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}
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