Pub Date : 2024-08-29DOI: 10.1038/s41565-024-01769-0
Yu Zhao, Jie Qin, Daohan Yu, Yuxiang Liu, Dan Song, Kaifu Tian, Hao Chen, Qile Ye, Xinyu Wang, Tianye Xu, Hanwen Xuan, Nan Sun, Wenbin Ma, Junzhe Zhong, Penggang Sun, Yu Song, Jingze Hu, Yunlei Zhao, Xintong Hou, Xiangqi Meng, Chuanlu Jiang, Jinquan Cai
In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR–Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood–brain barrier (BBB) and deliver short interfering RNA or CRISPR–Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a ‘lock’ into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR–Cas9 therapeutics. Delivering gene editing materials to the brain for glioblastoma therapy can boost the efficacy of chemotherapy. Here the authors reduce resistance to temozolomide using a reactive oxygen species-sensitive polymer-locking fusogenic liposome that can cross the blood–brain barrier and deliver short interfering RNA or CRISPR–Cas to glioblastoma with high specificity.
{"title":"Polymer-locking fusogenic liposomes for glioblastoma-targeted siRNA delivery and CRISPR–Cas gene editing","authors":"Yu Zhao, Jie Qin, Daohan Yu, Yuxiang Liu, Dan Song, Kaifu Tian, Hao Chen, Qile Ye, Xinyu Wang, Tianye Xu, Hanwen Xuan, Nan Sun, Wenbin Ma, Junzhe Zhong, Penggang Sun, Yu Song, Jingze Hu, Yunlei Zhao, Xintong Hou, Xiangqi Meng, Chuanlu Jiang, Jinquan Cai","doi":"10.1038/s41565-024-01769-0","DOIUrl":"10.1038/s41565-024-01769-0","url":null,"abstract":"In patients with glioblastoma (GBM), upregulated midkine (MDK) limits the survival benefits conferred by temozolomide (TMZ). RNA interference (RNAi) and CRISPR–Cas9 gene editing technology are attractive approaches for regulating MDK expression. However, delivering these biologics to GBM tissue is challenging. Here we demonstrate a polymer-locking fusogenic liposome (Plofsome) that can be transported across the blood–brain barrier (BBB) and deliver short interfering RNA or CRISPR–Cas9 ribonucleoprotein complexes into the cytoplasm of GBM cells. Plofsome is designed by integrating a ‘lock’ into the fusogenic liposome using a traceless reactive oxygen species (ROS)-cleavable linker so that fusion occurs only after crossing the BBB and entering the GBM tissue with high ROS levels. Our results showed that MDK suppression by Plofsomes significantly reduced TMZ resistance and inhibited GBM growth in orthotopic brain tumour models. Importantly, Plofsomes are effective only at tumour sites and not in normal tissues, which improves the safety of combined RNAi and CRISPR–Cas9 therapeutics. Delivering gene editing materials to the brain for glioblastoma therapy can boost the efficacy of chemotherapy. Here the authors reduce resistance to temozolomide using a reactive oxygen species-sensitive polymer-locking fusogenic liposome that can cross the blood–brain barrier and deliver short interfering RNA or CRISPR–Cas to glioblastoma with high specificity.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1869-1879"},"PeriodicalIF":38.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090263","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 : 2024-08-26DOI: 10.1038/s41565-024-01744-9
Kerstin Göpfrich, Michael Platten, Friedrich Frischknecht, Oliver T. Fackler
Infectious diseases and cancer evade immune surveillance using similar mechanisms. Targeting immune mechanisms using common strategies thus represents a promising avenue to improve prevention and treatment. Synthetic immunology can provide such strategies by applying engineering principles from synthetic biology to immunology. Synthetic biologists engineer cells by top-down genetic manipulation or bottom-up assembly from nanoscale building blocks. Recent successes in treating advanced tumours and diseases using genetically engineered immune cells highlight the power of the top-down synthetic immunology approach. However, genetic immune engineering is mostly limited to ex vivo applications and is subject to complex counter-regulation inherent to immune functions. Bottom-up synthetic biology can harness the rich nanotechnology toolbox to engineer molecular and cellular systems from scratch and equip them with desired functions. These are beginning to be tailored to perform targeted immune functions and should hence allow intervention strategies by rational design. In this Perspective we conceptualize bottom-up synthetic immunology as a new frontier field that uses nanotechnology for crucial innovations in therapy and the prevention of infectious diseases and cancer. This Perspective highlights bottom-up molecular engineering and modular nanobiotechnological approaches for developing effective immunotherapeutics and their potential in personalized medicine.
{"title":"Bottom-up synthetic immunology","authors":"Kerstin Göpfrich, Michael Platten, Friedrich Frischknecht, Oliver T. Fackler","doi":"10.1038/s41565-024-01744-9","DOIUrl":"10.1038/s41565-024-01744-9","url":null,"abstract":"Infectious diseases and cancer evade immune surveillance using similar mechanisms. Targeting immune mechanisms using common strategies thus represents a promising avenue to improve prevention and treatment. Synthetic immunology can provide such strategies by applying engineering principles from synthetic biology to immunology. Synthetic biologists engineer cells by top-down genetic manipulation or bottom-up assembly from nanoscale building blocks. Recent successes in treating advanced tumours and diseases using genetically engineered immune cells highlight the power of the top-down synthetic immunology approach. However, genetic immune engineering is mostly limited to ex vivo applications and is subject to complex counter-regulation inherent to immune functions. Bottom-up synthetic biology can harness the rich nanotechnology toolbox to engineer molecular and cellular systems from scratch and equip them with desired functions. These are beginning to be tailored to perform targeted immune functions and should hence allow intervention strategies by rational design. In this Perspective we conceptualize bottom-up synthetic immunology as a new frontier field that uses nanotechnology for crucial innovations in therapy and the prevention of infectious diseases and cancer. This Perspective highlights bottom-up molecular engineering and modular nanobiotechnological approaches for developing effective immunotherapeutics and their potential in personalized medicine.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1587-1596"},"PeriodicalIF":38.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073296","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 : 2024-08-26DOI: 10.1038/s41565-024-01758-3
Mixiao Tan, Guoliang Cao, Rupeng Wang, Long Cheng, Wenping Huang, Yue Yin, Haixia Ma, Shih-Hsin Ho, Zhigang Wang, Motao Zhu, Haitao Ran, Guangjun Nie, Hai Wang
An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving immune checkpoint blockade-based cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating l-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating l-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated cancer immunotherapy. Metal-ion-chelating phenylalanine nanostructures modulate ion influx and efflux in dendritic cells, activating them through the NLRP3 inflammasome and NF-κB pathway to remodel the immunosuppressive tumour microenvironment for PD-L1-based immunotherapy.
{"title":"Metal-ion-chelating phenylalanine nanostructures reverse immune dysfunction and sensitize breast tumour to immune checkpoint blockade","authors":"Mixiao Tan, Guoliang Cao, Rupeng Wang, Long Cheng, Wenping Huang, Yue Yin, Haixia Ma, Shih-Hsin Ho, Zhigang Wang, Motao Zhu, Haitao Ran, Guangjun Nie, Hai Wang","doi":"10.1038/s41565-024-01758-3","DOIUrl":"10.1038/s41565-024-01758-3","url":null,"abstract":"An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving immune checkpoint blockade-based cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating l-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating l-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated cancer immunotherapy. Metal-ion-chelating phenylalanine nanostructures modulate ion influx and efflux in dendritic cells, activating them through the NLRP3 inflammasome and NF-κB pathway to remodel the immunosuppressive tumour microenvironment for PD-L1-based immunotherapy.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1903-1913"},"PeriodicalIF":38.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073300","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}
Due to quasi-one-dimensional confinement, nanowires possess unique electronic properties, which can promote specific device architectures. However, nanowire growth presents paramount challenges, limiting the accessible crystal structures and elemental compositions. Here we demonstrate solid-state topotactic exchange that converts wurtzite InAs nanowires into Zintl Eu3In2As4. Molecular-beam-epitaxy-based in situ evaporation of Eu and As onto InAs nanowires results in the mutual exchange of Eu from the shell and In from the core. Therefore, a single-phase Eu3In2As4 shell grows, which gradually consumes the InAs core. The mutual exchange is supported by the substructure of the As matrix, which is similar across the wurtzite InAs and Zintl Eu3In2As4 and therefore is topotactic. The Eu3In2As4 nanowires undergo an antiferromagnetic transition at a Néel temperature of ~6.5 K. Ab initio calculations confirm the antiferromagnetic ground state and classify Eu3In2As4 as a C2T axion insulator, hosting both chiral hinge modes and unpinned Dirac surface states. The topotactic mutual-exchange nanowire growth will, thus, enable the exploration of intricate magneto-topological states in Eu3In2As4 and potentially in other exotic compounds. In situ evaporation of Eu and As onto InAs nanowires results in the mutual exchange of Eu from the shell with In from the core. This solid-state exchange reaction converts wurtzite InAs nanowires into Zintl Eu3In2As4.
由于准一维约束，纳米线具有独特的电子特性，可促进特定器件架构的发展。然而，纳米线的生长面临着巨大的挑战，限制了可获得的晶体结构和元素组成。在这里，我们展示了固态拓扑交换技术，它能将钨锆InAs纳米线转化为Zintl Eu3In2As4。基于分子束外延技术将 Eu 和 As 原位蒸发到 InAs 纳米线上，导致外壳的 Eu 和内核的 In 相互交换。因此，单相 Eu3In2As4 外壳逐渐生长，并逐渐消耗 InAs 内核。砷基质的亚结构支持了这种相互交换，这种亚结构在晶格InAs和Zintl Eu3In2As4中相似，因此具有拓扑结构。Ab initio 计算证实了反铁磁基态，并将 Eu3In2As4 归类为 C2T 轴向绝缘体，同时容纳了手性铰链模式和未钉住的狄拉克表面态。因此，拓扑相互交换纳米线生长将有助于探索 Eu3In2As4 以及其他奇异化合物中错综复杂的磁拓扑状态。
{"title":"Topotaxial mutual-exchange growth of magnetic Zintl Eu3In2As4 nanowires with axion insulator classification","authors":"Man Suk Song, Lothar Houben, Yufei Zhao, Hyeonhu Bae, Nadav Rothem, Ambikesh Gupta, Binghai Yan, Beena Kalisky, Magdalena Zaluska-Kotur, Perla Kacman, Hadas Shtrikman, Haim Beidenkopf","doi":"10.1038/s41565-024-01762-7","DOIUrl":"10.1038/s41565-024-01762-7","url":null,"abstract":"Due to quasi-one-dimensional confinement, nanowires possess unique electronic properties, which can promote specific device architectures. However, nanowire growth presents paramount challenges, limiting the accessible crystal structures and elemental compositions. Here we demonstrate solid-state topotactic exchange that converts wurtzite InAs nanowires into Zintl Eu3In2As4. Molecular-beam-epitaxy-based in situ evaporation of Eu and As onto InAs nanowires results in the mutual exchange of Eu from the shell and In from the core. Therefore, a single-phase Eu3In2As4 shell grows, which gradually consumes the InAs core. The mutual exchange is supported by the substructure of the As matrix, which is similar across the wurtzite InAs and Zintl Eu3In2As4 and therefore is topotactic. The Eu3In2As4 nanowires undergo an antiferromagnetic transition at a Néel temperature of ~6.5 K. Ab initio calculations confirm the antiferromagnetic ground state and classify Eu3In2As4 as a C2T axion insulator, hosting both chiral hinge modes and unpinned Dirac surface states. The topotactic mutual-exchange nanowire growth will, thus, enable the exploration of intricate magneto-topological states in Eu3In2As4 and potentially in other exotic compounds. In situ evaporation of Eu and As onto InAs nanowires results in the mutual exchange of Eu from the shell with In from the core. This solid-state exchange reaction converts wurtzite InAs nanowires into Zintl Eu3In2As4.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1796-1803"},"PeriodicalIF":38.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073301","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 : 2024-08-26DOI: 10.1038/s41565-024-01767-2
Andreas Aigner, Thomas Weber, Alwin Wester, Stefan A. Maier, Andreas Tittl
To control and enhance light–matter interactions at the nanoscale, two parameters are central: the spectral overlap between an optical cavity mode and the material’s spectral features (for example, excitonic or molecular absorption lines), and the quality factor of the cavity. Controlling both parameters simultaneously would enable the investigation of systems with complex spectral features, such as multicomponent molecular mixtures or heterogeneous solid-state materials. So far, it has been possible only to sample a limited set of data points within this two-dimensional parameter space. Here we introduce a nanophotonic approach that can simultaneously and continuously encode the spectral and quality-factor parameter space within a compact spatial area. We use a dual-gradient metasurface design composed of a two-dimensional array of smoothly varying subwavelength nanoresonators, each supporting a unique mode based on symmetry-protected bound states in the continuum. This results in 27,500 distinct modes and a mode density approaching the theoretical upper limit for metasurfaces. By applying our platform to surface-enhanced molecular spectroscopy, we find that the optimal quality factor for maximum sensitivity depends on the amount of analyte, enabling effective molecular detection regardless of analyte concentration within a single dual-gradient metasurface. Our design provides a method to analyse the complete spectral and coupling-strength parameter space of complex material systems for applications such as photocatalysis, chemical sensing and entangled photon generation. A dual-gradient metasurface is introduced that allows continuous control over light–matter coupling in the spectral and quality-factor parameter space. Used for molecular sensing, it achieves mode densities near the theoretical limit for metasurfaces.
{"title":"Continuous spectral and coupling-strength encoding with dual-gradient metasurfaces","authors":"Andreas Aigner, Thomas Weber, Alwin Wester, Stefan A. Maier, Andreas Tittl","doi":"10.1038/s41565-024-01767-2","DOIUrl":"10.1038/s41565-024-01767-2","url":null,"abstract":"To control and enhance light–matter interactions at the nanoscale, two parameters are central: the spectral overlap between an optical cavity mode and the material’s spectral features (for example, excitonic or molecular absorption lines), and the quality factor of the cavity. Controlling both parameters simultaneously would enable the investigation of systems with complex spectral features, such as multicomponent molecular mixtures or heterogeneous solid-state materials. So far, it has been possible only to sample a limited set of data points within this two-dimensional parameter space. Here we introduce a nanophotonic approach that can simultaneously and continuously encode the spectral and quality-factor parameter space within a compact spatial area. We use a dual-gradient metasurface design composed of a two-dimensional array of smoothly varying subwavelength nanoresonators, each supporting a unique mode based on symmetry-protected bound states in the continuum. This results in 27,500 distinct modes and a mode density approaching the theoretical upper limit for metasurfaces. By applying our platform to surface-enhanced molecular spectroscopy, we find that the optimal quality factor for maximum sensitivity depends on the amount of analyte, enabling effective molecular detection regardless of analyte concentration within a single dual-gradient metasurface. Our design provides a method to analyse the complete spectral and coupling-strength parameter space of complex material systems for applications such as photocatalysis, chemical sensing and entangled photon generation. A dual-gradient metasurface is introduced that allows continuous control over light–matter coupling in the spectral and quality-factor parameter space. Used for molecular sensing, it achieves mode densities near the theoretical limit for metasurfaces.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1804-1812"},"PeriodicalIF":38.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01767-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073297","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 : 2024-08-26DOI: 10.1038/s41565-024-01768-1
Tram Thi Hong Le, Byoung Choul Kim
DNA origami tension sensors, created by integrating DNA origami sheets with molecular tension probes, enable the quantification of mechanical forces involved in T cell receptor interactions at intermembrane junctions.
DNA 折纸张力传感器是通过将 DNA 折纸片材与分子张力探针整合在一起而制作的，能够量化 T 细胞受体在膜间连接处相互作用时所产生的机械力。
{"title":"DNA origami force probes illuminate T cell receptor forces at the immune synapse","authors":"Tram Thi Hong Le, Byoung Choul Kim","doi":"10.1038/s41565-024-01768-1","DOIUrl":"10.1038/s41565-024-01768-1","url":null,"abstract":"DNA origami tension sensors, created by integrating DNA origami sheets with molecular tension probes, enable the quantification of mechanical forces involved in T cell receptor interactions at intermembrane junctions.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1583-1584"},"PeriodicalIF":38.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073298","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}
Biomolecule-based non-covalent glasses are biocompatible and biodegradable, and offer a sustainable alternative to conventional glass. Cyclic peptides (CPs) can serve as promising glass formers owing to their structural rigidity and resistance to enzymatic degradation. However, their potent crystallization tendency hinders their potential in glass construction. Here we engineered a series of CP glasses with tunable glass transition behaviours by modulating the conformational complexity of CP clusters. By incorporating multicomponent CPs, the formation of high-entropy CP glass is facilitated, which—in turn—inhibits the crystallization of individual CPs. The high-entropy CP glass demonstrates enhanced mechanical properties and enzyme tolerance compared with individual CP glass and a unique biorecycling capability that is unattainable by traditional glasses. These findings provide a promising paradigm for the design and development of stable non-covalent glasses based on naturally derived biomolecules, and advance their application in pharmaceutical formulations and smart functional materials. Biodegradable glasses are a sustainable alternative to traditional glass. Here high-entropy cyclic peptide glasses are engineered, with enhanced crystallization resistance, mechanical properties and enzyme tolerance.
{"title":"High-entropy non-covalent cyclic peptide glass","authors":"Chengqian Yuan, Wei Fan, Peng Zhou, Ruirui Xing, Shuai Cao, Xuehai Yan","doi":"10.1038/s41565-024-01766-3","DOIUrl":"10.1038/s41565-024-01766-3","url":null,"abstract":"Biomolecule-based non-covalent glasses are biocompatible and biodegradable, and offer a sustainable alternative to conventional glass. Cyclic peptides (CPs) can serve as promising glass formers owing to their structural rigidity and resistance to enzymatic degradation. However, their potent crystallization tendency hinders their potential in glass construction. Here we engineered a series of CP glasses with tunable glass transition behaviours by modulating the conformational complexity of CP clusters. By incorporating multicomponent CPs, the formation of high-entropy CP glass is facilitated, which—in turn—inhibits the crystallization of individual CPs. The high-entropy CP glass demonstrates enhanced mechanical properties and enzyme tolerance compared with individual CP glass and a unique biorecycling capability that is unattainable by traditional glasses. These findings provide a promising paradigm for the design and development of stable non-covalent glasses based on naturally derived biomolecules, and advance their application in pharmaceutical formulations and smart functional materials. Biodegradable glasses are a sustainable alternative to traditional glass. Here high-entropy cyclic peptide glasses are engineered, with enhanced crystallization resistance, mechanical properties and enzyme tolerance.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1840-1848"},"PeriodicalIF":38.1,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073299","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 : 2024-08-23DOI: 10.1038/s41565-024-01765-4
Sheng Zhao, Kewa Gao, Hesong Han, Michael Stenzel, Boyan Yin, Hengyue Song, Atip Lawanprasert, Josefine Eilsø Nielsen, Rohit Sharma, Opeyemi H. Arogundade, Sopida Pimcharoen, Yu-Ju Chen, Abhik Paul, Jan Tuma, Michael G. Collins, Yofiel Wyle, Matileen Grace Cranick, Benjamin W. Burgstone, Barbara S. Perez, Annelise E. Barron, Andrew M. Smith, Hye Young Lee, Aijun Wang, Niren Murthy
Lipid nanoparticle (LNP)–mRNA complexes are transforming medicine. However, the medical applications of LNPs are limited by their low endosomal disruption rates, high toxicity and long tissue persistence times. LNPs that rapidly hydrolyse in endosomes (RD-LNPs) could solve the problems limiting LNP-based therapeutics and dramatically expand their applications but have been challenging to synthesize. Here we present an acid-degradable linker termed ‘azido-acetal’ that hydrolyses in endosomes within minutes and enables the production of RD-LNPs. Acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids and cationic lipids were synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improved the performance of LNP–mRNA complexes in vitro and in vivo. Collectively, RD-LNPs delivered mRNA more efficiently to the liver, lung, spleen and brains of mice and to haematopoietic stem and progenitor cells in vitro than conventional LNPs. These experiments demonstrate that engineering LNP hydrolysis rates in vivo has great potential for expanding the medical applications of LNPs. A new acid-degradable linker termed ‘azido-acetal’ has been developed that rapidly hydrolyses at pH 6.0 but is stable at pH 7.4. Lipid nanoparticles made with this linker delivered mRNA in vivo and in vitro better than traditional lipid nanoparticles.
{"title":"Acid-degradable lipid nanoparticles enhance the delivery of mRNA","authors":"Sheng Zhao, Kewa Gao, Hesong Han, Michael Stenzel, Boyan Yin, Hengyue Song, Atip Lawanprasert, Josefine Eilsø Nielsen, Rohit Sharma, Opeyemi H. Arogundade, Sopida Pimcharoen, Yu-Ju Chen, Abhik Paul, Jan Tuma, Michael G. Collins, Yofiel Wyle, Matileen Grace Cranick, Benjamin W. Burgstone, Barbara S. Perez, Annelise E. Barron, Andrew M. Smith, Hye Young Lee, Aijun Wang, Niren Murthy","doi":"10.1038/s41565-024-01765-4","DOIUrl":"10.1038/s41565-024-01765-4","url":null,"abstract":"Lipid nanoparticle (LNP)–mRNA complexes are transforming medicine. However, the medical applications of LNPs are limited by their low endosomal disruption rates, high toxicity and long tissue persistence times. LNPs that rapidly hydrolyse in endosomes (RD-LNPs) could solve the problems limiting LNP-based therapeutics and dramatically expand their applications but have been challenging to synthesize. Here we present an acid-degradable linker termed ‘azido-acetal’ that hydrolyses in endosomes within minutes and enables the production of RD-LNPs. Acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids and cationic lipids were synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improved the performance of LNP–mRNA complexes in vitro and in vivo. Collectively, RD-LNPs delivered mRNA more efficiently to the liver, lung, spleen and brains of mice and to haematopoietic stem and progenitor cells in vitro than conventional LNPs. These experiments demonstrate that engineering LNP hydrolysis rates in vivo has great potential for expanding the medical applications of LNPs. A new acid-degradable linker termed ‘azido-acetal’ has been developed that rapidly hydrolyses at pH 6.0 but is stable at pH 7.4. Lipid nanoparticles made with this linker delivered mRNA in vivo and in vitro better than traditional lipid nanoparticles.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1702-1711"},"PeriodicalIF":38.1,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142042625","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 : 2024-08-23DOI: 10.1038/s41565-024-01763-6
J. Ryan Nolen, Adam C. Overvig, Michele Cotrufo, Andrea Alù
Thermal emission from a hot body is inherently challenging to control due to its incoherent nature. Recent advances have shown that patterned surfaces can transform thermal emission into partially coherent beams with tailored directionality and frequency selectivity. Here we experimentally demonstrate polarization-selective, unidirectional and narrowband thermal emission using single-layer metasurfaces. By implementing polarization gradients across the surface, we unveil a generalization of the photonic Rashba effect from circular polarizations to any pair of orthogonal polarizations and apply it to thermal emission. Leveraging pointwise specification of arbitrary elliptical polarization, we implement a thermal geometric phase and leverage it to prove previous theoretical predictions that asymmetric chiral emission is possible without violating reciprocity. This general platform can be extended to other frequency regimes in efforts to compactify metasurface optics technologies without the need for external coherent sources. A metasurface is used to generalize the Rashba effect from circular polarizations to any polarization state for thermal emission.
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Pub Date : 2024-08-22DOI: 10.1038/s41565-024-01771-6
Kevin N. Lin, Kevin Volkel, Cyrus Cao, Paul W. Hook, Rachel E. Polak, Andrew S. Clark, Adriana San Miguel, Winston Timp, James M. Tuck, Orlin D. Velev, Albert J. Keung
Any modern information system is expected to feature a set of primordial features and functions: a substrate stably carrying data; the ability to repeatedly write, read, erase, reload and compute on specific data from that substrate; and the overall ability to execute such functions in a seamless and programmable manner. For nascent molecular information technologies, proof-of-principle realization of this set of primordial capabilities would advance the vision for their continued development. Here we present a DNA-based store and compute engine that captures these primordial capabilities. This system comprises multiple image files encoded into DNA and adsorbed onto ~50-μm-diameter, highly porous, hierarchically branched, colloidal substrate particles comprised of naturally abundant cellulose acetate. Their surface areas are over 200 cm2 mg−1 with binding capacities of over 1012 DNA oligos mg−1, 10 TB mg−1 or 104 TB cm−3. This ‘dendricolloid’ stably holds DNA files better than bare DNA with an extrapolated ability to be repeatedly lyophilized and rehydrated over 170 times compared with 60 times, respectively. Accelerated ageing studies project half-lives of ~6,000 and 2 million years at 4 °C and −18 °C, respectively. The data can also be erased and replaced, and non-destructive file access is achieved through transcribing from distinct synthetic promoters. The resultant RNA molecules can be directly read via nanopore sequencing and can also be enzymatically computed to solve simplified 3 × 3 chess and sudoku problems. Our study establishes a feasible route for utilizing the high information density and parallel computational advantages of nucleic acids. Here, the authors present a data storage and computation engine comprised of DNA adsorbed to soft dendricolloids, demonstrating end-to-end capabilities from archival storage to non-destructive file access for reading, erasing, rewriting and computing.
任何现代信息系统都应具备一系列基本特征和功能：稳定承载数据的基底；对该基底的特定数据进行反复写入、读取、擦除、重新加载和计算的能力；以及以无缝和可编程方式执行这些功能的整体能力。对于新生的分子信息技术来说，实现这一系列原始能力的原理性证明将推动它们的持续发展。在这里，我们展示了一个基于 DNA 的存储和计算引擎，它捕捉到了这些原始能力。该系统由多个图像文件组成，这些图像文件被编码到 DNA 中，并吸附在直径约 50 微米、多孔、分层支化、胶体基质颗粒上，这些颗粒由天然丰富的醋酸纤维素组成。它们的表面积超过 200 cm2 mg-1，结合能力超过 1012 DNA 寡聚 mg-1、10 TB mg-1 或 104 TB cm-3。这种 "树枝状胶体 "比裸 DNA 更能稳定地保存 DNA 文件，其反复冻干和再水化的推断能力分别超过 170 次和 60 次。加速老化研究预测，在 4 °C 和 -18 °C 温度下，半衰期分别为 6000 年和 200 万年。数据还可以擦除和替换，并通过从不同的合成启动子转录实现非破坏性文件访问。由此产生的 RNA 分子可以通过纳米孔测序直接读取，也可以通过酶计算来解决简化的 3 × 3 国际象棋和数独问题。我们的研究为利用核酸的高信息密度和并行计算优势确立了一条可行的途径。
{"title":"A primordial DNA store and compute engine","authors":"Kevin N. Lin, Kevin Volkel, Cyrus Cao, Paul W. Hook, Rachel E. Polak, Andrew S. Clark, Adriana San Miguel, Winston Timp, James M. Tuck, Orlin D. Velev, Albert J. Keung","doi":"10.1038/s41565-024-01771-6","DOIUrl":"10.1038/s41565-024-01771-6","url":null,"abstract":"Any modern information system is expected to feature a set of primordial features and functions: a substrate stably carrying data; the ability to repeatedly write, read, erase, reload and compute on specific data from that substrate; and the overall ability to execute such functions in a seamless and programmable manner. For nascent molecular information technologies, proof-of-principle realization of this set of primordial capabilities would advance the vision for their continued development. Here we present a DNA-based store and compute engine that captures these primordial capabilities. This system comprises multiple image files encoded into DNA and adsorbed onto ~50-μm-diameter, highly porous, hierarchically branched, colloidal substrate particles comprised of naturally abundant cellulose acetate. Their surface areas are over 200 cm2 mg−1 with binding capacities of over 1012 DNA oligos mg−1, 10 TB mg−1 or 104 TB cm−3. This ‘dendricolloid’ stably holds DNA files better than bare DNA with an extrapolated ability to be repeatedly lyophilized and rehydrated over 170 times compared with 60 times, respectively. Accelerated ageing studies project half-lives of ~6,000 and 2 million years at 4 °C and −18 °C, respectively. The data can also be erased and replaced, and non-destructive file access is achieved through transcribing from distinct synthetic promoters. The resultant RNA molecules can be directly read via nanopore sequencing and can also be enzymatically computed to solve simplified 3 × 3 chess and sudoku problems. Our study establishes a feasible route for utilizing the high information density and parallel computational advantages of nucleic acids. Here, the authors present a data storage and computation engine comprised of DNA adsorbed to soft dendricolloids, demonstrating end-to-end capabilities from archival storage to non-destructive file access for reading, erasing, rewriting and computing.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 11","pages":"1654-1664"},"PeriodicalIF":38.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142022216","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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