Midori Johnston, Schan Dissanayake-Perera, James J Collins, Molly M Stevens, Can Dincer
{"title":"Convergence of nanotechnology and CRISPR-based diagnostics.","authors":"Midori Johnston, Schan Dissanayake-Perera, James J Collins, Molly M Stevens, Can Dincer","doi":"10.1038/s41565-025-02018-8","DOIUrl":"https://doi.org/10.1038/s41565-025-02018-8","url":null,"abstract":"<p><p>In addition to its broad application in genome engineering and therapeutics, clustered regularly interspaced short palindromic repeats (CRISPR) technology provides field-deployable methods for the highly sensitive and selective detection of nucleic acids. From a diagnostic perspective, CRISPR-based assays hold clear clinical potential for identifying a range of both infectious and non-communicable diseases. In this Perspective we evaluate recent nanotechnologies and nanomaterials that have been engineered to interface with CRISPR systems on a nanoscale level to realize the full potential of this versatile diagnostic tool. We assess biomolecules such as enzymes and oligonucleotides, some of the more commonly used synthetic nanoparticles and detection platforms that integrate nanotechnologies in new and innovative ways. We discuss current trends and look ahead to future challenges and opportunities, including non-nucleic acid target detection, pre-amplification-free detection of nucleic acids, the development of wearable devices and integration with artificial intelligence workflows.</p>","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":" ","pages":""},"PeriodicalIF":34.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213080","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}
{"title":"Spatiotemporal-adaptive nanotherapeutics promote post-injury regeneration in ageing through metabolic modulation.","authors":"Kaiyu Liang,Lan Zhao,Shuheng Zhang,Luyu Zheng,Zheyuan Zhang,Shengyu Wang,Junxin Chen,Wenbin Xu,Weikai Wang,Hanshen Yang,Chenxin Song,Pengcheng Qiu,Chenchen Zhao,Weifeng Fang,Jinjin Zhu,Shunwu Fan,Zhaoming Liu,Ruikang Tang,Yueqi Zhao,Xiangqian Fang","doi":"10.1038/s41565-025-02017-9","DOIUrl":"https://doi.org/10.1038/s41565-025-02017-9","url":null,"abstract":"In the elderly population, dysregulated cellular behaviour during the healing process impacts tissue regeneration after injury. Early in the regeneration process, pro-inflammatory macrophages contribute to immune imbalance, while in later stages, senescent stem cells reduce regenerative capacity. Here we demonstrate that nicotinamide adenine dinucleotide (NAD+) can reprogramme both types of dysfunctional cell. We developed a spatiotemporal-adaptive nanotherapeutic system for the delivery of NAD+ into selected cells during different phases of tissue repair. By replenishing intracellular NAD+ pools, this system reshapes the multicellular regeneration niche, by metabolically rewiring pro-inflammatory macrophages towards a pro-repair phenotype during the early phase, and enhancing the differentiation capacity of senescent stem cells at later stages. This strategy effectively restored impaired bone regeneration in osteoporotic mice and accelerated skin wound healing. Our work presents a spatiotemporal-adaptive nanomedicine platform that bridges cell metabolism, nanomedicine and regeneration therapy.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"124 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203628","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}
Yingying Wu,Bin Li,Xiang Zhu,Zhengya Wang,Ruoting Yin,Zhenfa Zheng,Bowen Zhao,Honghui Shang,Qing-Song Deng,Yuan-Zhi Tan,Yao Zhang,Chuanxu Ma,Shijing Tan,Yi Luo,Jinlong Yang,J G Hou,Bing Wang
{"title":"Polaron superlattices in n-doped single conjugated polymers.","authors":"Yingying Wu,Bin Li,Xiang Zhu,Zhengya Wang,Ruoting Yin,Zhenfa Zheng,Bowen Zhao,Honghui Shang,Qing-Song Deng,Yuan-Zhi Tan,Yao Zhang,Chuanxu Ma,Shijing Tan,Yi Luo,Jinlong Yang,J G Hou,Bing Wang","doi":"10.1038/s41565-025-02019-7","DOIUrl":"https://doi.org/10.1038/s41565-025-02019-7","url":null,"abstract":"The presence of multiple polarons, particularly at high doping levels, involves complex many-body interactions that substantially influence the electronic and transport properties of various materials. Determining the spatial distributions of coupled electronic and vibrational states is essential to understanding interacting polarons at a microscopic level but remains a challenge. Here we report the crystallization of electron polarons into quasi-one-dimensional polaron superlattices in highly n-doped single ethynylene-bonded polypentacenes. We employ integrated scanning tunnelling microscopy, atomic force microscopy and tip-enhanced Raman spectroscopy combined with first-principles density functional theory to correlate electronic, vibrational and structural information. The observed polaron superlattices exhibit different periodicities that depend on the doping levels. Their real-space polaron wavefunctions are determined by the intertwined electronic and vibrational periodic modulations associated with the periodic lattice distortions as resolved by atomic force microscopy. We can then identify the multiband charge-density-wave attributes of interacting polarons in these superlattices. Our findings provide microscopic insights in interacting polarons, which is important for the understanding of polaronic charge transport mechanisms in organic semiconductors.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"37 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134307","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}
{"title":"Meso-macroporous hydrogel for direct litre-scale isolation of extracellular vesicles.","authors":"Junbeom Kim,Minjin Kang,Geonhee Han,Sujin Hyung,Mina Kim,Minjeong Jang,Han Kyul Lee,Yunhee Seo,Ki Cheol Gil,Changheon Kim,Sojin Song,Seonghyeok Jeong,Seongchan Kim,Min Soo Kim,Ji Sung Shim,Sung Gu Kang,Young Chan Lee,Seok Chung,Il-Joo Cho,Tae Soup Shim,Kwang Hoon Song,Jouha Min,Hyejeong Seong,Kyungeun Lee,Jeeyun Lee,Cheolju Lee,Hong Nam Kim,Hyojin Lee,Sun Hwa Kim,Ji Yoon Kang,Ki Wan Bong,Nakwon Choi","doi":"10.1038/s41565-025-02011-1","DOIUrl":"https://doi.org/10.1038/s41565-025-02011-1","url":null,"abstract":"Extracellular vesicles are cell-originated lipid bilayer membrane vesicles that play vital roles in cell-to-cell communications. While extracellular vesicles hold substantial biomedical potential, conventional methodologies for isolating extracellular vesicles require elaborate preprocessing and, therefore, remain labour intensive and limited by throughput. To overcome these challenges, we present a facile fabrication route for generating a meso-macroporous hydrogel matrix with pores of ~400 nm for customizable extracellular vesicle isolation. By combining surface charge-selective capture of extracellular vesicles within the hydrogel matrix and their recovery by high ionic strength, we report direct extracellular vesicle isolation with a throughput range from microlitre to litre scales, without preprocessing, for various biofluids, including whole blood, plasma, ascites, saliva, urine, bovine milk and cell culture media. Furthermore, we demonstrate that the meso-macroporous hydrogel also serves as a solid-phase matrix for preserving extracellular vesicles for on-demand downstream analyses, making it applicable for therapeutics, cosmeceuticals and disease diagnostics.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"87 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134574","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}
Neeraj Soni,Zohar Rosenstock,Navneet C Verma,Krishnan Siddharth,Noam Talor,Jingqian Liu,Barak Marom,Anatoly B Kolomeisky,Aleksei Aksimentiev,Amit Meller
{"title":"Full-length protein classification via cysteine fingerprinting in solid-state nanopores.","authors":"Neeraj Soni,Zohar Rosenstock,Navneet C Verma,Krishnan Siddharth,Noam Talor,Jingqian Liu,Barak Marom,Anatoly B Kolomeisky,Aleksei Aksimentiev,Amit Meller","doi":"10.1038/s41565-025-02016-w","DOIUrl":"https://doi.org/10.1038/s41565-025-02016-w","url":null,"abstract":"Recent advances in single-molecule technologies are transforming the field of protein analysis. Solid-state nanopores provide an effective method to linearize and thread full-length proteins in a single file. However, slowing their rapid translocation remains a challenge for accurate, time-resolved ion-current-based fingerprinting. In this work, we present a click-chemistry-based strategy for covalently attaching short oligonucleotides to cysteine residues on denatured proteins across a broad range of molecular weights. The negatively charged oligonucleotides increase the capture rate by a factor of ten compared with native proteins and induce a distinct 'stick-slip' motion that slows protein passage through the nanopore by more than 20-fold. These oligonucleotide tags also produce characteristic, time-resolved ion current pulses that serve as unique protein-specific signatures. To uncover the physical mechanism responsible for the protein translocation dynamics, we model our system using all-atom molecular dynamics and finite element simulations. By leveraging a supervised machine learning classifier, we demonstrate that a small number of translocation events is sufficient to identify individual proteins, achieving near-perfect classification accuracy. To demonstrate the robustness of the method, we successfully distinguish between VEGF-A isoforms (VEGF-165 and VEGF-121), which are relevant to cancer diagnostics, within a mixed protein sample. Our nanopore-based fingerprinting technique eliminates the need for affinity reagents, such as protein-specific antibodies, or motor proteins, offering a rapid, direct and cost-effective approach for single-molecule protein identification and classification.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"95 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134308","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}
{"title":"Breaking symmetry in time to protect light.","authors":"Mikael C Rechtsman,Nathan Goldman","doi":"10.1038/s41565-025-02012-0","DOIUrl":"https://doi.org/10.1038/s41565-025-02012-0","url":null,"abstract":"","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"18 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134309","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}
{"title":"Setting a direction for molecular recognition.","authors":"Thomas E Ouldridge,Rakesh Mukherjee","doi":"10.1038/s41565-025-01997-y","DOIUrl":"https://doi.org/10.1038/s41565-025-01997-y","url":null,"abstract":"","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"86 1","pages":""},"PeriodicalIF":38.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089816","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}