Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint de...Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint delivery of nanovaccines(ADN)to elicit dual-niche immunological priming.ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes.We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α^(+)dendritic cells,but also induces the accumulation of nanovaccines in B-cell zones,amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen.Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice,ADN provides a simple yet versatile platform for advanced nanovaccination.展开更多
Metal structures with special shapes at the length scales of electromagnetic waves,particularly visible light(~10^(–7)m),hold great promise in the development of next-generation electronic/optical devices.However,dow...Metal structures with special shapes at the length scales of electromagnetic waves,particularly visible light(~10^(–7)m),hold great promise in the development of next-generation electronic/optical devices.However,downscaling the metal structure features to the sub-10 nm scale remains a challenge due to the resolution lim-itations inherent in conventional top-down microfabrication techniques.In recent years,DNA nanotechnology has garnered significant attention due to its capability to construct nanostructures with programmable shapes at the nanometer scale,which can serve as templates for the fabrication of metal nanostructures.Here,we review the development of DNA-templated metal nanostructures with unique shapes,focusing on their electronic and optical properties and applications.We discuss the advantages and limitations of these strategies and provide an outlook for this research area.展开更多
Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabricat...Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabrication and high driving voltages.Sensor integration in DMF systems is also quite rare.In this study,a programmable magnetic digital microfluidic(PMDMF)platform integrated with electrochemical detection system was proposed.It enables non-contact,flexible droplet manipulation without complex processes and high voltages,meeting the requirements of automated electrochemical detection.The platform includes a magnetic control system,a microfluidic chip,and an electrochemical detection system.The magnetic control system consists of a microcoil array circuit board,a N52 permanent magnet,and an Arduino control module.N52 magnets generate localized magnetic fields to drive droplet movement,while the Arduino module enables programmable control for precise manipulation.The maximum average velocity of the droplet is about 3.9 cm/s.The microfluidic chip was fabricated using 3D printing and the superhydrophobic surface of chip was fabricated by spray coating.The electrochemical detection system consists of the MoS_(2)@CeO_(2)/PVA working electrode,Ag/AgCl reference electrode,and carbon counter electrode.To evaluate the practical value of the integrated platform,glucose in sweat was automatically and accurately detected.The proposed platform has a wide linear detection range(0.01–0.25 mM),a lower LOD(6.5μM),a superior sensitivity(7833.54μA·mM^(−1)·cm^(−2)),and excellent recovery rate(88.1-113.5%).It has an extensive potential for future application in the fields of medical diagnostics and point-of-care testing.展开更多
DNA nanostructures,with their high structural programmability and excellent biocompatibility,have shown tremendous potential in biomedicine applications.This review provides an overview of the self-assembly principles...DNA nanostructures,with their high structural programmability and excellent biocompatibility,have shown tremendous potential in biomedicine applications.This review provides an overview of the self-assembly principles underlying DNA nanostructures,with a particular focus on the current techniques for intracellular tracking,highlighting their advantages and limitations.Building on this foundation,the intracellular behaviors and fates of DNA nanostructures are discussed,along with their potential applications in biomedicine.Finally,future research directions are proposed,offering insights and guidance for the continued development of DNA nanostructures in biomedical fields.展开更多
DNA hydrogels are three-dimensional polymer networks constructed using DNA as the structural building block.Due to the tight binding between hydrophilic groups on DNA chains and water molecules,they exhibit outstandin...DNA hydrogels are three-dimensional polymer networks constructed using DNA as the structural building block.Due to the tight binding between hydrophilic groups on DNA chains and water molecules,they exhibit outstanding plasticity and fluid thermodynamic properties,making them one of the best choices for mimicking natural biological tissues.By controlling the backbone building blocks,gelation conditions,and cross-linking methods of DNA hydrogels,hydrogels with different mechanical strengths can be obtained,thus expanding their applications in the field of biology.This review first introduces the relationship between the mechanical properties of DNA hydrogels and their structure,elucidates the approaches and strategies for mechanical property modulation,and focuses on the scheme of controllable design to modulate the mechanical properties of DNA hydrogels for applications in biosensing,cellular function regulation,and bone tissue engineering.Furthermore,this review outlines the future development directions and challenges faced in the mechanical property modulation of DNA hydrogels,providing useful information for the precise design of DNA hydrogels for biological research.展开更多
The functionalization of living cells,both internally and externally,transforming them into microma-chines with specified functions,holds significant po-tential in fields such as biosensing,biocomputing,and intelligen...The functionalization of living cells,both internally and externally,transforming them into microma-chines with specified functions,holds significant po-tential in fields such as biosensing,biocomputing,and intelligent theranostics.However,due to the complexity and dynamic nature of living cells,it remains challenging to allocate exogenous function-al materials to specific locations within the cell or on its surface and maintain their positions stable for a reasonable period.Here,we devise a DNA-pro-grammed cargo distributing system(DCD),capable of distributing functional modules to the cell mem-brane or within the cell as needed.This system includes an amphiphilic DNA structure for determin-ing the destination of the cargo and a DNA connector carried on it for recognizing the DNA-encoded cargo.We test three different morphologies of amphiphilic DNA structures and find that their efficiencies in cell surface retention and cell internalization significantly varied,enabling the distribution of nanoparticle cargos on the cell membrane and within the cell in distinct proportions.Their positions can remain sta-ble for at least 6 h.Moreover,this allocation method shows specificity,which minimizes the deployment of mismatched cargo.This method provides new tools for the modular construction of cellular micro-machines.展开更多
Idiopathic pulmonary fibrosis(IPF)is an irreversible and fatal lung disease characterized by persistent alveolar epithelial cell injury and extracellular matrix deposition.Early dual modulation of oxidative stress and...Idiopathic pulmonary fibrosis(IPF)is an irreversible and fatal lung disease characterized by persistent alveolar epithelial cell injury and extracellular matrix deposition.Early dual modulation of oxidative stress and inflammation may offer a promising therapeutic opportunity.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)offer therapeutic promise but face challenges in scalability and efficient lung delivery.Here,we developed a biomimetic extracellular vesicle-spherical nucleic acid(BEV-SNA)platform for IPF therapy.BEV-SNA were constructed by integrating mechanically extruded BEVs fromprimary MSCs with cholesterol-modified ssDNA through hydrophobic co-assembly.In stemness-maintained P0-P1 MSCs,the production of BEVs increased by 17.2-fold compared to natural EVs.Benefiting from a three-dimensionally dense and negatively charged DNA shell,BEV-SNA reduce airway adhesion,enabling deep pulmonary delivery and efficient cellular uptake.In IPF models,BEVSNA demonstrated multiphase therapeutic effects,including protection of alveolar epithelial cells from ROS,anti-inflammatory activity,and late-stage anti-fibrotic action,effectively halting fibrosis progression and achieving a 50%survival rate in mice.This study presents a novel therapeutic platform combining the natural biomimicry of EVs with the functional adaptability of SNAs,proposing an innovative strategy for pulmonary drug delivery and the treatment of respiratory diseases.展开更多
With the advancement of modern science and technology, large scientific facilities are increasingly oriented toward demand and application, and can be used for basic research as well as serving multiple disciplines. D...With the advancement of modern science and technology, large scientific facilities are increasingly oriented toward demand and application, and can be used for basic research as well as serving multiple disciplines. Developing large scientific facilities and related analytical technologies enhances understanding of large scientific facilities and popularizes their application in research across multiple disciplines. The combination of light or neutron sources from large scientific facilities and advanced analytical technologies can be achieved for materials structure information, dynamics study of chemical reactions, high dissociation of biomolecules, 3D visualization of energy materials or biological samples, etc. We first introduce the progress of domestic large scientific facilities of synchrotron radiation(SR) and free electron lasers(FELs) with different wavelengths and neutron sources.We further discuss the comparison between Chinese and typical foreign facilities in X-ray radiation from X-ray tubes, synchrotrons, X-ray FELs, and neutron sources based on physical parameters of light and neutron sources. In addition, we focus on the technological progress and perspectives combined with advanced X-ray radiation and neutron sources of large scientific facilities in China, especially in the nanoscience fields of energy catalysis and biological science. We hope that this roadmap will provide references on technology and methods to experimental users, as well as prospects for future development of technologies based on large research infrastructure facilities. Comprehensive studies and guidelines for basic research to practical application in various disciplines can be made with the assistance of large scientific facilities.展开更多
Airborne diseases including SARS,bird flu,and the ongoing Coronavirus Disease 2019(COVID-19)have stimulated the demand for developing novel bioassay methods competent for early-stage diagnosis and large-scale screenin...Airborne diseases including SARS,bird flu,and the ongoing Coronavirus Disease 2019(COVID-19)have stimulated the demand for developing novel bioassay methods competent for early-stage diagnosis and large-scale screening.Here,we briefly summarize the state-of-the-art methods for the detection of infectious pathogens and discuss key challenges.We highlight the trend for next-generation technologies benefiting from multidisciplinary advances in microfabrication,nanotechnology and synthetic biology,which allow sensitive,rapid yet inexpensive pathogen assays with portable intelligent device.展开更多
DNA nanostructures have emerged as promising carriers for drug delivery.However,challenges such as low stability,poor cellular uptake efficiency,and vulnerability to lysosomal degradation still hinder their therapeuti...DNA nanostructures have emerged as promising carriers for drug delivery.However,challenges such as low stability,poor cellular uptake efficiency,and vulnerability to lysosomal degradation still hinder their therapeutic potential.In this study,we demonstrate the coating of tetrahedral DNA frameworks(TDF)with the endosomolytic peptide L17E through electrostatic interactions to address these issues.Our findings highlight that L17E coating substantially enhances the stability of TDFs and improves their uptake efficiency into RAW264.7 cells through endocytosis and macropinocytosis.Moreover,L17E coating enables efficient endosomal release of TDFs.Finally,we employed L17E-coated TDF to deliver osteogenic growth peptide and demonstrated its potential applications in inhibiting periodontitis both in vitro and in vivo.This straightforward and cost-effective strategy holds promise for advancing the biomedical applications of DNA nanostructures.展开更多
基金supported by the National Key Research and Development Program of China(2021YFA0909400)the National Natural Science Foundation of China(22425505,32301099,and 21834007)+2 种基金the Shanghai Sailing Program(22YF1424200)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2022QN032)the Xiangfu Lab Research Project(XF012022E0100).
文摘Immunization has long played essential roles in preventing diseases.However,the desire for precision delivery of vaccines to boost a robust immune response remains largely unmet.Here,we describe the use of acupoint delivery of nanovaccines(ADN)to elicit dual-niche immunological priming.ADN can simultaneously stimulate mast cell-assisted maturation of dendritic cells at the acupoint and enable direct delivery of nanovaccines into the draining lymph nodes.We demonstrate that ADN not only provokes antigen presentation by lymph node-resident CD8α^(+)dendritic cells,but also induces the accumulation of nanovaccines in B-cell zones,amplifying antigen-specific cytotoxic T lymphocyte responses and immunoglobulin G antibody expression in draining lymph nodes.ADN also generates systemic immune responses by causing immune memory and preventing T-cell anergy in the spleen.Further supported by evoking effective antitumor responses and high-level antiviral antibodies in mice,ADN provides a simple yet versatile platform for advanced nanovaccination.
基金support from the National Key Research and Development Program of China(2023YFB3208200)the China Postdoctoral Science Foundation(2022M722711).
文摘Metal structures with special shapes at the length scales of electromagnetic waves,particularly visible light(~10^(–7)m),hold great promise in the development of next-generation electronic/optical devices.However,downscaling the metal structure features to the sub-10 nm scale remains a challenge due to the resolution lim-itations inherent in conventional top-down microfabrication techniques.In recent years,DNA nanotechnology has garnered significant attention due to its capability to construct nanostructures with programmable shapes at the nanometer scale,which can serve as templates for the fabrication of metal nanostructures.Here,we review the development of DNA-templated metal nanostructures with unique shapes,focusing on their electronic and optical properties and applications.We discuss the advantages and limitations of these strategies and provide an outlook for this research area.
基金supported by grants from the National Key Research and Development Program of China(No.2023YFB3208200)the equipment research and development projects of the Chinese Academy of Sciences(PTYQ2024YZ0010)+3 种基金the Science and Technology Commission of Shanghai Municipality Project(XTCX-KJ-2024-038)National Natural Science Foundation of China(62401555)Shanghai Science and Technology Development Funds(23J21900100)supported by the Postdoctoral Fellowship Program of CPSF under Grant Number GZC20232838.
文摘Digital microfluidic(DMF)technology is widely used in bioanalysis and chemical reactions due to its accuracy and flexibility in manipulating droplets.However,most DMF systems usually rely on complex electrode fabrication and high driving voltages.Sensor integration in DMF systems is also quite rare.In this study,a programmable magnetic digital microfluidic(PMDMF)platform integrated with electrochemical detection system was proposed.It enables non-contact,flexible droplet manipulation without complex processes and high voltages,meeting the requirements of automated electrochemical detection.The platform includes a magnetic control system,a microfluidic chip,and an electrochemical detection system.The magnetic control system consists of a microcoil array circuit board,a N52 permanent magnet,and an Arduino control module.N52 magnets generate localized magnetic fields to drive droplet movement,while the Arduino module enables programmable control for precise manipulation.The maximum average velocity of the droplet is about 3.9 cm/s.The microfluidic chip was fabricated using 3D printing and the superhydrophobic surface of chip was fabricated by spray coating.The electrochemical detection system consists of the MoS_(2)@CeO_(2)/PVA working electrode,Ag/AgCl reference electrode,and carbon counter electrode.To evaluate the practical value of the integrated platform,glucose in sweat was automatically and accurately detected.The proposed platform has a wide linear detection range(0.01–0.25 mM),a lower LOD(6.5μM),a superior sensitivity(7833.54μA·mM^(−1)·cm^(−2)),and excellent recovery rate(88.1-113.5%).It has an extensive potential for future application in the fields of medical diagnostics and point-of-care testing.
基金supported by the National Key R&D Program of China(2023YFB3208200)the National Natural Science Foundation of China(T2188102,22325406,22204100,32301185)+1 种基金the 2022 Shanghai"Science and Technology Innovation Action Plan"Fundamental Research Project(22JC1401203)Open Project of National Major Scientific and Technological Infrastructure for Translational Medicine(Shanghai,TMSK-2024-201).
文摘DNA nanostructures,with their high structural programmability and excellent biocompatibility,have shown tremendous potential in biomedicine applications.This review provides an overview of the self-assembly principles underlying DNA nanostructures,with a particular focus on the current techniques for intracellular tracking,highlighting their advantages and limitations.Building on this foundation,the intracellular behaviors and fates of DNA nanostructures are discussed,along with their potential applications in biomedicine.Finally,future research directions are proposed,offering insights and guidance for the continued development of DNA nanostructures in biomedical fields.
基金supported by the National Key Research and Development Program of China(2023YFB3208204)the National Natural Science Foundation of China(12305400,12105352)+2 种基金the Natural Science Foundation of Shanghai,China(22ZR1470600)the Natural Science Foundation of Shandong Province(ZR2019MB068,ZR2022MB012,ZR2021QE167)the Xiangfu Lab Research Project(XF012022E0100).
文摘DNA hydrogels are three-dimensional polymer networks constructed using DNA as the structural building block.Due to the tight binding between hydrophilic groups on DNA chains and water molecules,they exhibit outstanding plasticity and fluid thermodynamic properties,making them one of the best choices for mimicking natural biological tissues.By controlling the backbone building blocks,gelation conditions,and cross-linking methods of DNA hydrogels,hydrogels with different mechanical strengths can be obtained,thus expanding their applications in the field of biology.This review first introduces the relationship between the mechanical properties of DNA hydrogels and their structure,elucidates the approaches and strategies for mechanical property modulation,and focuses on the scheme of controllable design to modulate the mechanical properties of DNA hydrogels for applications in biosensing,cellular function regulation,and bone tissue engineering.Furthermore,this review outlines the future development directions and challenges faced in the mechanical property modulation of DNA hydrogels,providing useful information for the precise design of DNA hydrogels for biological research.
基金supported by the National Key R&D Program of China(grant no.2020YFA0908900)the National Natural Science Foundation of China(grant nos.22105124,22325406,21934007,21991134,T2188102)+1 种基金2022 Shanghai“Science and Technology Innovation Action Plan”Fundamental Research Project(grant no.22JC1401203)the New Cornerstone Science Foundation,and the Open Research Fund of the National Facility for Translational Medicine(Shanghai,grant no.TMSK-2021-412).
文摘The functionalization of living cells,both internally and externally,transforming them into microma-chines with specified functions,holds significant po-tential in fields such as biosensing,biocomputing,and intelligent theranostics.However,due to the complexity and dynamic nature of living cells,it remains challenging to allocate exogenous function-al materials to specific locations within the cell or on its surface and maintain their positions stable for a reasonable period.Here,we devise a DNA-pro-grammed cargo distributing system(DCD),capable of distributing functional modules to the cell mem-brane or within the cell as needed.This system includes an amphiphilic DNA structure for determin-ing the destination of the cargo and a DNA connector carried on it for recognizing the DNA-encoded cargo.We test three different morphologies of amphiphilic DNA structures and find that their efficiencies in cell surface retention and cell internalization significantly varied,enabling the distribution of nanoparticle cargos on the cell membrane and within the cell in distinct proportions.Their positions can remain sta-ble for at least 6 h.Moreover,this allocation method shows specificity,which minimizes the deployment of mismatched cargo.This method provides new tools for the modular construction of cellular micro-machines.
基金supported by the National Key R&D Program of China(2020YFA0908900 to J.L.)the National Natural Science Foundation of China(Nos.U24A20377,82170074,22325406)+4 种基金the Zhejiang Provincial Nature Science Foundation of China(No.Y24H010013)the the Ningbo Science and Technological Innovation Yongjiang 2035 Major Project(No.2024Z183)the Ningbo Clinical Research Center for Respiratory Disease(No.2022L004)the Ningbo Natural Science Foundation(No.2022J241)the Ningbo Yongjiang Talent Introduction Programme(No.2023A-114-G).
文摘Idiopathic pulmonary fibrosis(IPF)is an irreversible and fatal lung disease characterized by persistent alveolar epithelial cell injury and extracellular matrix deposition.Early dual modulation of oxidative stress and inflammation may offer a promising therapeutic opportunity.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)offer therapeutic promise but face challenges in scalability and efficient lung delivery.Here,we developed a biomimetic extracellular vesicle-spherical nucleic acid(BEV-SNA)platform for IPF therapy.BEV-SNA were constructed by integrating mechanically extruded BEVs fromprimary MSCs with cholesterol-modified ssDNA through hydrophobic co-assembly.In stemness-maintained P0-P1 MSCs,the production of BEVs increased by 17.2-fold compared to natural EVs.Benefiting from a three-dimensionally dense and negatively charged DNA shell,BEV-SNA reduce airway adhesion,enabling deep pulmonary delivery and efficient cellular uptake.In IPF models,BEVSNA demonstrated multiphase therapeutic effects,including protection of alveolar epithelial cells from ROS,anti-inflammatory activity,and late-stage anti-fibrotic action,effectively halting fibrosis progression and achieving a 50%survival rate in mice.This study presents a novel therapeutic platform combining the natural biomimicry of EVs with the functional adaptability of SNAs,proposing an innovative strategy for pulmonary drug delivery and the treatment of respiratory diseases.
基金supported by the National Basic Research Program of China (2022YFA1603701, 2021YFA1200900)the institutionalized scientific research platform relies on Beijing Synchrotron Radiation Facility of Chinese Academy of Sciences,the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000)+2 种基金the National Natural Science Foundation of China (22027810, 82341044,22388101 and 22307028)the CAMS Innovation Fund for Medical Sciences(CIFMS 2019-I2M-5-018)the New Cornerstone Science Foundation。
文摘With the advancement of modern science and technology, large scientific facilities are increasingly oriented toward demand and application, and can be used for basic research as well as serving multiple disciplines. Developing large scientific facilities and related analytical technologies enhances understanding of large scientific facilities and popularizes their application in research across multiple disciplines. The combination of light or neutron sources from large scientific facilities and advanced analytical technologies can be achieved for materials structure information, dynamics study of chemical reactions, high dissociation of biomolecules, 3D visualization of energy materials or biological samples, etc. We first introduce the progress of domestic large scientific facilities of synchrotron radiation(SR) and free electron lasers(FELs) with different wavelengths and neutron sources.We further discuss the comparison between Chinese and typical foreign facilities in X-ray radiation from X-ray tubes, synchrotrons, X-ray FELs, and neutron sources based on physical parameters of light and neutron sources. In addition, we focus on the technological progress and perspectives combined with advanced X-ray radiation and neutron sources of large scientific facilities in China, especially in the nanoscience fields of energy catalysis and biological science. We hope that this roadmap will provide references on technology and methods to experimental users, as well as prospects for future development of technologies based on large research infrastructure facilities. Comprehensive studies and guidelines for basic research to practical application in various disciplines can be made with the assistance of large scientific facilities.
基金This work was financially supported by the National Natural Science Foundation of China(21991134,91953106)Science Foundation of the Shanghai Municipal Science and Technology Commission(19JC1410300,21dz2210100)。
文摘Airborne diseases including SARS,bird flu,and the ongoing Coronavirus Disease 2019(COVID-19)have stimulated the demand for developing novel bioassay methods competent for early-stage diagnosis and large-scale screening.Here,we briefly summarize the state-of-the-art methods for the detection of infectious pathogens and discuss key challenges.We highlight the trend for next-generation technologies benefiting from multidisciplinary advances in microfabrication,nanotechnology and synthetic biology,which allow sensitive,rapid yet inexpensive pathogen assays with portable intelligent device.
基金supported by the National Key R&D Program of China(2020YFA0908900)Universities Stable Funding Key Projects(WDZC20200821104802001)+2 种基金the State Key Laboratory of Chemical Oncogenomicsthe Institute of Biomedical Health Technology and Engineering of Shenzhen Bay LaboratoryGuangDong Basic and Applied Basic Research Foundation(2021A1515110819).
文摘DNA nanostructures have emerged as promising carriers for drug delivery.However,challenges such as low stability,poor cellular uptake efficiency,and vulnerability to lysosomal degradation still hinder their therapeutic potential.In this study,we demonstrate the coating of tetrahedral DNA frameworks(TDF)with the endosomolytic peptide L17E through electrostatic interactions to address these issues.Our findings highlight that L17E coating substantially enhances the stability of TDFs and improves their uptake efficiency into RAW264.7 cells through endocytosis and macropinocytosis.Moreover,L17E coating enables efficient endosomal release of TDFs.Finally,we employed L17E-coated TDF to deliver osteogenic growth peptide and demonstrated its potential applications in inhibiting periodontitis both in vitro and in vivo.This straightforward and cost-effective strategy holds promise for advancing the biomedical applications of DNA nanostructures.
