Pub Date : 2024-10-11DOI: 10.1038/s41565-024-01798-9
Ye Ji Kim, Noah Kent, Emmanuel Vargas Paniagua, Nicolette Driscoll, Anthony Tabet, Florian Koehler, Elian Malkin, Ethan Frey, Marie Manthey, Atharva Sahasrabudhe, Taylor M. Cannon, Keisuke Nagao, David Mankus, Margaret Bisher, Giovanni de Nola, Abigail Lytton-Jean, Lorenzo Signorelli, Danijela Gregurec, Polina Anikeeva
Deep brain stimulation with implanted electrodes has transformed neuroscience studies and treatment of neurological and psychiatric conditions. Discovering less invasive alternatives to deep brain stimulation could expand its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials has been explored as a means for remote neuromodulation. Here we synthesize magnetoelectric nanodiscs (MENDs) with a core–double-shell Fe3O4–CoFe2O4–BaTiO3 architecture (250 nm diameter and 50 nm thickness) with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg mm−2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization that, combined with cable theory, supports our observations in vitro and informs magnetoelectric stimulation in vivo. Injected into the ventral tegmental area or the subthalamic nucleus of genetically intact mice at concentrations of 1 mg ml−1, MENDs enable remote control of reward or motor behaviours, respectively. These findings set the stage for mechanistic optimization of magnetoelectric neuromodulation towards applications in neuroscience research. In this study, the authors present magnetoelectric nanodiscs that enable minimally invasive, remote magnetic neuromodulation with subsecond precision to drive reward and motor behaviours in genetically intact mice.
{"title":"Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation","authors":"Ye Ji Kim, Noah Kent, Emmanuel Vargas Paniagua, Nicolette Driscoll, Anthony Tabet, Florian Koehler, Elian Malkin, Ethan Frey, Marie Manthey, Atharva Sahasrabudhe, Taylor M. Cannon, Keisuke Nagao, David Mankus, Margaret Bisher, Giovanni de Nola, Abigail Lytton-Jean, Lorenzo Signorelli, Danijela Gregurec, Polina Anikeeva","doi":"10.1038/s41565-024-01798-9","DOIUrl":"10.1038/s41565-024-01798-9","url":null,"abstract":"Deep brain stimulation with implanted electrodes has transformed neuroscience studies and treatment of neurological and psychiatric conditions. Discovering less invasive alternatives to deep brain stimulation could expand its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials has been explored as a means for remote neuromodulation. Here we synthesize magnetoelectric nanodiscs (MENDs) with a core–double-shell Fe3O4–CoFe2O4–BaTiO3 architecture (250 nm diameter and 50 nm thickness) with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg mm−2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization that, combined with cable theory, supports our observations in vitro and informs magnetoelectric stimulation in vivo. Injected into the ventral tegmental area or the subthalamic nucleus of genetically intact mice at concentrations of 1 mg ml−1, MENDs enable remote control of reward or motor behaviours, respectively. These findings set the stage for mechanistic optimization of magnetoelectric neuromodulation towards applications in neuroscience research. In this study, the authors present magnetoelectric nanodiscs that enable minimally invasive, remote magnetic neuromodulation with subsecond precision to drive reward and motor behaviours in genetically intact mice.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"121-131"},"PeriodicalIF":38.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01798-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404903","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 : 2024-10-09DOI: 10.1038/s41565-024-01772-5
Maria Fernanda Campa, Craig M. Brown, Peter Byrley, Jason Delborne, Nicholas Glavin, Craig Green, Mark Griep, Tina Kaarsberg, Igor Linkov, Jeffrey B. Miller, Joshua E. Porterfield, Birgit Schwenzer, Quinn Spadola, Branden Brough, James A. Warren
Climate change is one of humankind’s biggest challenges, leading to more frequent and intense climate extremes, including heatwaves, wildfires, hurricanes, ocean acidification, and increased extinction rates. Nanotechnology already plays an important role in decarbonizing critical processes. Still, despite the technical advances seen in the last decades, the International Energy Agency has identified many sectors that are not on track to achieve the global climate mitigation goals by 2030. Here, a multi-stakeholder group of nanoscientists from the public, private, and philanthropic sectors discuss four high-potential application spaces where nanotechnologies could accelerate progress: batteries and energy storage; catalysis; coatings, lubricants, membranes, and other interface technology; and capture of greenhouse gases. This Comment highlights opportunities and current gaps for those working to minimize the climate crisis and provides a framework for the nanotechnology community to answer the call to action on this global issue.
{"title":"Nanotechnology solutions for the climate crisis","authors":"Maria Fernanda Campa, Craig M. Brown, Peter Byrley, Jason Delborne, Nicholas Glavin, Craig Green, Mark Griep, Tina Kaarsberg, Igor Linkov, Jeffrey B. Miller, Joshua E. Porterfield, Birgit Schwenzer, Quinn Spadola, Branden Brough, James A. Warren","doi":"10.1038/s41565-024-01772-5","DOIUrl":"10.1038/s41565-024-01772-5","url":null,"abstract":"Climate change is one of humankind’s biggest challenges, leading to more frequent and intense climate extremes, including heatwaves, wildfires, hurricanes, ocean acidification, and increased extinction rates. Nanotechnology already plays an important role in decarbonizing critical processes. Still, despite the technical advances seen in the last decades, the International Energy Agency has identified many sectors that are not on track to achieve the global climate mitigation goals by 2030. Here, a multi-stakeholder group of nanoscientists from the public, private, and philanthropic sectors discuss four high-potential application spaces where nanotechnologies could accelerate progress: batteries and energy storage; catalysis; coatings, lubricants, membranes, and other interface technology; and capture of greenhouse gases. This Comment highlights opportunities and current gaps for those working to minimize the climate crisis and provides a framework for the nanotechnology community to answer the call to action on this global issue.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 10","pages":"1422-1426"},"PeriodicalIF":38.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41565-024-01772-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385131","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 : 2024-10-08DOI: 10.1038/s41565-024-01786-z
Tapas R. Nayak, Adrian Chrastina, Jose Valencia, Oscar Cordova-Robles, Robert Yedidsion, Tim Buss, Brittany Cederstrom, Jim Koziol, Michael D. Levin, Bogdan Olenyuk, Jan E. Schnitzer
Modern medicine seeks precision targeting, imaging and therapy to maximize efficacy and avoid toxicities. Nanoparticles (NPs) have tremendous yet unmet clinical potential to carry and deliver imaging and therapeutic agents systemically with tissue precision. But their size contributes to rapid scavenging by the reticuloendothelial system and poor penetration of key endothelial cell (EC) barriers, limiting target tissue uptake, safety and efficacy. Here we discover the ability of the EC caveolae pumping system to outpace scavenging and deliver NPs rapidly and specifically into the lungs. Gold and dendritic NPs are conjugated to antibodies targeting caveolae of the lung microvascular endothelium. SPECT-CT imaging and biodistribution analyses reveal that rat lungs extract most of the intravenous dose within minutes to achieve precision lung imaging and targeting with high lung concentrations exceeding peak blood levels. These results reveal how much ECs can both limit and promote tissue penetration of NPs and the power and size-dependent limitations of the caveolae pumping system. This study provides a new retargeting paradigm for NPs to avoid reticuloendothelial system uptake and achieve rapid precision nanodelivery for future diagnostic and therapeutic applications. Reducing scavenging of nanoparticles by the reticuloendothelial system and increasing their penetration through endothelial cell barriers would increase their clinical potential. Here the authors show that small nanoparticles targeting the caveolae of the lung microvascular endothelium are rapidly delivered to the lungs for precision imaging and targeting.
{"title":"Rapid precision targeting of nanoparticles to lung via caveolae pumping system in endothelium","authors":"Tapas R. Nayak, Adrian Chrastina, Jose Valencia, Oscar Cordova-Robles, Robert Yedidsion, Tim Buss, Brittany Cederstrom, Jim Koziol, Michael D. Levin, Bogdan Olenyuk, Jan E. Schnitzer","doi":"10.1038/s41565-024-01786-z","DOIUrl":"10.1038/s41565-024-01786-z","url":null,"abstract":"Modern medicine seeks precision targeting, imaging and therapy to maximize efficacy and avoid toxicities. Nanoparticles (NPs) have tremendous yet unmet clinical potential to carry and deliver imaging and therapeutic agents systemically with tissue precision. But their size contributes to rapid scavenging by the reticuloendothelial system and poor penetration of key endothelial cell (EC) barriers, limiting target tissue uptake, safety and efficacy. Here we discover the ability of the EC caveolae pumping system to outpace scavenging and deliver NPs rapidly and specifically into the lungs. Gold and dendritic NPs are conjugated to antibodies targeting caveolae of the lung microvascular endothelium. SPECT-CT imaging and biodistribution analyses reveal that rat lungs extract most of the intravenous dose within minutes to achieve precision lung imaging and targeting with high lung concentrations exceeding peak blood levels. These results reveal how much ECs can both limit and promote tissue penetration of NPs and the power and size-dependent limitations of the caveolae pumping system. This study provides a new retargeting paradigm for NPs to avoid reticuloendothelial system uptake and achieve rapid precision nanodelivery for future diagnostic and therapeutic applications. Reducing scavenging of nanoparticles by the reticuloendothelial system and increasing their penetration through endothelial cell barriers would increase their clinical potential. Here the authors show that small nanoparticles targeting the caveolae of the lung microvascular endothelium are rapidly delivered to the lungs for precision imaging and targeting.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"144-155"},"PeriodicalIF":38.1,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384302","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 : 2024-10-07DOI: 10.1038/s41565-024-01795-y
M. Kravtsov, A. L. Shilov, Y. Yang, T. Pryadilin, M. A. Kashchenko, O. Popova, M. Titova, D. Voropaev, Y. Wang, K. Shein, I. Gayduchenko, G. N. Goltsman, M. Lukianov, A. Kudriashov, T. Taniguchi, K. Watanabe, D. A. Svintsov, S. Adam, K. S. Novoselov, A. Principi, D. A. Bandurin
Light incident upon materials can induce changes in their electrical conductivity, a phenomenon referred to as photoresistance. In semiconductors, the photoresistance is negative, as light-induced promotion of electrons across the bandgap enhances the number of charge carriers participating in transport. In superconductors and normal metals, the photoresistance is positive because of the destruction of the superconducting state and enhanced momentum-relaxing scattering, respectively. Here we report a qualitative deviation from the standard behaviour in doped metallic graphene. We show that Dirac electrons exposed to continuous-wave terahertz (THz) radiation can be thermally decoupled from the lattice, which activates hydrodynamic electron transport. In this regime, the resistance of graphene constrictions experiences a decrease caused by the THz-driven superballistic flow of correlated electrons. We analyse the dependencies of the negative photoresistance on the carrier density, and the radiation power, and show that our superballistic devices operate as sensitive phonon-cooled bolometers and can thus offer, in principle, a picosecond-scale response time. Beyond their fundamental implications, our findings underscore the practicality of electron hydrodynamics in designing ultra-fast THz sensors and electron thermometers. Terahertz absorption reduces the viscosity of the hydrodynamic electron fluid in graphene and thereby enables easier flow of electrons. This results in a drop in resistance within graphene constrictions under terahertz radiation, facilitating fast and sensitive terahertz detection.
{"title":"Viscous terahertz photoconductivity of hydrodynamic electrons in graphene","authors":"M. Kravtsov, A. L. Shilov, Y. Yang, T. Pryadilin, M. A. Kashchenko, O. Popova, M. Titova, D. Voropaev, Y. Wang, K. Shein, I. Gayduchenko, G. N. Goltsman, M. Lukianov, A. Kudriashov, T. Taniguchi, K. Watanabe, D. A. Svintsov, S. Adam, K. S. Novoselov, A. Principi, D. A. Bandurin","doi":"10.1038/s41565-024-01795-y","DOIUrl":"10.1038/s41565-024-01795-y","url":null,"abstract":"Light incident upon materials can induce changes in their electrical conductivity, a phenomenon referred to as photoresistance. In semiconductors, the photoresistance is negative, as light-induced promotion of electrons across the bandgap enhances the number of charge carriers participating in transport. In superconductors and normal metals, the photoresistance is positive because of the destruction of the superconducting state and enhanced momentum-relaxing scattering, respectively. Here we report a qualitative deviation from the standard behaviour in doped metallic graphene. We show that Dirac electrons exposed to continuous-wave terahertz (THz) radiation can be thermally decoupled from the lattice, which activates hydrodynamic electron transport. In this regime, the resistance of graphene constrictions experiences a decrease caused by the THz-driven superballistic flow of correlated electrons. We analyse the dependencies of the negative photoresistance on the carrier density, and the radiation power, and show that our superballistic devices operate as sensitive phonon-cooled bolometers and can thus offer, in principle, a picosecond-scale response time. Beyond their fundamental implications, our findings underscore the practicality of electron hydrodynamics in designing ultra-fast THz sensors and electron thermometers. Terahertz absorption reduces the viscosity of the hydrodynamic electron fluid in graphene and thereby enables easier flow of electrons. This results in a drop in resistance within graphene constrictions under terahertz radiation, facilitating fast and sensitive terahertz detection.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"51-56"},"PeriodicalIF":38.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383634","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 : 2024-10-07DOI: 10.1038/s41565-024-01799-8
Donghwan Koo, Yunseong Choi, Ungsoo Kim, Jihyun Kim, Jihyung Seo, Eunbin Son, Hanul Min, Joohoon Kang, Hyesung Park
Mesoporous structured electron transport layers (ETLs) in perovskite solar cells (PSCs) have an increased surface contact with the perovskite layer, enabling effective charge separation and extraction, and high-efficiency devices. However, the most widely used ETL material in PSCs, TiO2, requires a sintering temperature of more than 500 °C and undergoes photocatalytic reaction under incident illumination that limits operational stability. Recent efforts have focused on finding alternative ETL materials, such as SnO2. Here we propose mesoporous MoS2 as an efficient and stable ETL material. The MoS2 interlayer increases the surface contact area with the adjacent perovskite layer, improving charge transfer dynamics between the two layers. In addition, the matching between the MoS2 and the perovskite lattices facilitates preferential growth of perovskite crystals with low residual strain, compared with TiO2. Using mesoporous structured MoS2 as ETL, we obtain PSCs with 25.7% (0.08 cm2, certified 25.4%) and 22.4% (1.00 cm2) efficiencies. Under continuous illumination, our cell remains stable for more than 2,000 h, demonstrating improved photostability with respect to TiO2. Mesoporous MoS2 is proposed as an efficient electron transport layer in perovskite solar cells, achieving efficiencies >25% with over 2,000 h of stable operation.
{"title":"Mesoporous structured MoS2 as an electron transport layer for efficient and stable perovskite solar cells","authors":"Donghwan Koo, Yunseong Choi, Ungsoo Kim, Jihyun Kim, Jihyung Seo, Eunbin Son, Hanul Min, Joohoon Kang, Hyesung Park","doi":"10.1038/s41565-024-01799-8","DOIUrl":"10.1038/s41565-024-01799-8","url":null,"abstract":"Mesoporous structured electron transport layers (ETLs) in perovskite solar cells (PSCs) have an increased surface contact with the perovskite layer, enabling effective charge separation and extraction, and high-efficiency devices. However, the most widely used ETL material in PSCs, TiO2, requires a sintering temperature of more than 500 °C and undergoes photocatalytic reaction under incident illumination that limits operational stability. Recent efforts have focused on finding alternative ETL materials, such as SnO2. Here we propose mesoporous MoS2 as an efficient and stable ETL material. The MoS2 interlayer increases the surface contact area with the adjacent perovskite layer, improving charge transfer dynamics between the two layers. In addition, the matching between the MoS2 and the perovskite lattices facilitates preferential growth of perovskite crystals with low residual strain, compared with TiO2. Using mesoporous structured MoS2 as ETL, we obtain PSCs with 25.7% (0.08 cm2, certified 25.4%) and 22.4% (1.00 cm2) efficiencies. Under continuous illumination, our cell remains stable for more than 2,000 h, demonstrating improved photostability with respect to TiO2. Mesoporous MoS2 is proposed as an efficient electron transport layer in perovskite solar cells, achieving efficiencies >25% with over 2,000 h of stable operation.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 1","pages":"75-82"},"PeriodicalIF":38.1,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383635","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 : 2024-10-03DOI: 10.1038/s41565-024-01753-8
Lang Rao, Yuan Yuan, Xi Shen, Guocan Yu, Xiaoyuan Chen
The inherent limits of traditional diagnoses and therapies have driven the development and application of emerging nanotechnologies for more effective and safer management of diseases, herein referred to as ‘nanotheranostics’. Although many important technological successes have been achieved in this field, widespread adoption of nanotheranostics as a new paradigm is hindered by specific obstacles, including time-consuming synthesis of nanoparticles, incomplete understanding of nano–bio interactions, and challenges regarding chemistry, manufacturing and the controls required for clinical translation and commercialization. As a key branch of artificial intelligence, machine learning (ML) provides a set of tools capable of performing time-consuming and result-perception tasks, thus offering unique opportunities for nanotheranostics. This Review summarizes the progress and challenges in this emerging field of ML-aided nanotheranostics, and discusses the opportunities in developing next-generation nanotheranostics with reliable datasets and advanced ML models to offer better clinical benefits to patients. This Review explores how machine learning approaches can drive progress in nanotheranostics.
{"title":"Designing nanotheranostics with machine learning","authors":"Lang Rao, Yuan Yuan, Xi Shen, Guocan Yu, Xiaoyuan Chen","doi":"10.1038/s41565-024-01753-8","DOIUrl":"10.1038/s41565-024-01753-8","url":null,"abstract":"The inherent limits of traditional diagnoses and therapies have driven the development and application of emerging nanotechnologies for more effective and safer management of diseases, herein referred to as ‘nanotheranostics’. Although many important technological successes have been achieved in this field, widespread adoption of nanotheranostics as a new paradigm is hindered by specific obstacles, including time-consuming synthesis of nanoparticles, incomplete understanding of nano–bio interactions, and challenges regarding chemistry, manufacturing and the controls required for clinical translation and commercialization. As a key branch of artificial intelligence, machine learning (ML) provides a set of tools capable of performing time-consuming and result-perception tasks, thus offering unique opportunities for nanotheranostics. This Review summarizes the progress and challenges in this emerging field of ML-aided nanotheranostics, and discusses the opportunities in developing next-generation nanotheranostics with reliable datasets and advanced ML models to offer better clinical benefits to patients. This Review explores how machine learning approaches can drive progress in nanotheranostics.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"19 12","pages":"1769-1781"},"PeriodicalIF":38.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369435","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 : 2024-10-01DOI: 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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：