{"title":"The benefits and risks of PEGylation in nanomedicine","authors":"","doi":"10.1038/s41565-025-01951-y","DOIUrl":"10.1038/s41565-025-01951-y","url":null,"abstract":"Polyethylene glycol (PEG) is a commonly used coating agent in nanomedicine, but there are growing concerns about its immunogenicity. Two Comment articles discuss the issue and possible alternatives to PEG.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 5","pages":"575-575"},"PeriodicalIF":34.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41565-025-01951-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087895","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}
Yali Wu, Wenjuan Chen, Jingjing Deng, Xinghui Cao, Zimo Yang, Jiangbin Chen, Qi Tan, E. Zhou, Minglei Li, Jiatong Liu, Mengfei Guo, Yang Jin
{"title":"Tumour-derived microparticles obtained through microwave irradiation induce immunogenic cell death in lung adenocarcinoma","authors":"Yali Wu, Wenjuan Chen, Jingjing Deng, Xinghui Cao, Zimo Yang, Jiangbin Chen, Qi Tan, E. Zhou, Minglei Li, Jiatong Liu, Mengfei Guo, Yang Jin","doi":"10.1038/s41565-025-01922-3","DOIUrl":"10.1038/s41565-025-01922-3","url":null,"abstract":"Tumour-derived microparticles (TMPs), extracellular vesicles traditionally obtained upon ultraviolet (UV) radiation of tumour cells, hold promise in tumour immunotherapies and vaccines and have demonstrated potential as drug delivery systems for tumour treatment. However, concerns remain regarding the limited efficacy and safety of UV-derived TMPs. Here we introduce a microwave (MW)-assisted method for preparing TMPs, termed MW-TMPs. Brief exposure of tumour cells to short-wavelength MW radiation promotes the release of TMPs showing superior in vivo antitumour activity and safety compared with UV-TMPs. MW-TMPs induce immunogenic cell death and reprogramme suppressive tumour immune microenvironments in different lung tumour models, enabling dual targeting of tumour cells by natural killer and T cells. We show that they can efficiently deliver methotrexate to tumours, synergistically boosting the efficacy of PD-L1 blockade. This MW-TMP development strategy is simpler, more efficient and safer than traditional UV-TMP methods. Microwave-assisted tumour-derived microparticles enhance antitumour activity, safety and drug delivery, outperforming traditional ultraviolet-derived methods.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 8","pages":"1119-1130"},"PeriodicalIF":34.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41565-025-01922-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087898","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}
{"title":"Engineering pyroptotic vesicles as personalized cancer vaccines","authors":"Zhaoting Li, Yixin Wang, Fanyi Mo, Tyler Wolter, Rachel Hong, Allie Barrett, Nathaniel Richmond, Fengyuan Liu, Yu Chen, Xicheng Yang, Lauren Dempsey, Quanyin Hu","doi":"10.1038/s41565-025-01931-2","DOIUrl":"10.1038/s41565-025-01931-2","url":null,"abstract":"Tumour vaccines are designed to stimulate the host’s immune system against existing tumours or tumour recurrence. However, individual differences, tumour heterogeneity and side effects hinder the applications of current tumour vaccines and require the development of personalized cancer vaccines. To overcome these challenges, we engineered pyroptotic vesicles—extracellular vesicles formed during tumour cell pyroptosis—as a tumour vaccine platform. The extracted pyroptotic vesicles possess abundant tumour antigens and potent immune-stimulating ability and, loaded into a biocompatible hydrogel, they can be implanted into post-surgical tumour cavities to prevent tumour recurrence. The pyroptotic-vesicle-based vaccine outperforms both exosome- and apoptotic-body-based vaccines in inhibiting tumour recurrence and metastasis in different post-surgical mouse models. Mechanistic studies reveal that the pyroptotic-vesicle-based vaccine could stimulate robust antigen-specific dendritic cell and T cell immune responses against both artificial OVA antigens and cancer neoantigens. In sum, our vaccine platform can be tailored to stimulate robust antitumour immune responses for treating individual cancer patients. Engineered pyroptotic vesicles formed during tumour cell pyroptosis and engineered as personalized tumour vaccines can activate a robust antitumour immune response for post-surgical tumour recurrence inhibition.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 8","pages":"1108-1118"},"PeriodicalIF":34.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066081","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}
Songyue Chen, Xiujun Fan, Zhaoqi Duan, Yang Luo, Jun Chen
{"title":"A magnetically programmable mesoporous nanoreactor","authors":"Songyue Chen, Xiujun Fan, Zhaoqi Duan, Yang Luo, Jun Chen","doi":"10.1038/s41565-025-01910-7","DOIUrl":"10.1038/s41565-025-01910-7","url":null,"abstract":"Engineering magnetic nanoparticles at the single-particle level advances nanoreactor design, enabling enhanced active sensing, targeted therapy, and catalytic activity, with broad implications for nano energy and nanomedicine applications.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 7","pages":"861-862"},"PeriodicalIF":34.9,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066187","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}
Bram Bussin, Marshall G. G. MacDuff, Wayne Ngo, Jamie L. Y. Wu, Zachary P. Lin, Adrian Granda Farias, Benjamin Stordy, Zahra Sepahi, Sara Ahmed, Jason Moffat, Warren C. W. Chan
{"title":"Discovering nanoparticle corona ligands for liver macrophage capture","authors":"Bram Bussin, Marshall G. G. MacDuff, Wayne Ngo, Jamie L. Y. Wu, Zachary P. Lin, Adrian Granda Farias, Benjamin Stordy, Zahra Sepahi, Sara Ahmed, Jason Moffat, Warren C. W. Chan","doi":"10.1038/s41565-025-01903-6","DOIUrl":"10.1038/s41565-025-01903-6","url":null,"abstract":"Liver macrophages capture circulating nanoparticles and reduce their delivery to target organs. Serum proteins adsorb to the nanoparticle surface after administration. However, the adsorbed serum proteins and their cognate cell receptors for removing nanoparticles from the bloodstream have not been linked. Here we use a multi-omics strategy to identify the adsorbed serum proteins binding to specific liver macrophage receptors. We discovered six absorbed serum proteins that bind to two liver macrophage receptors. Nanoparticle physicochemical properties can affect the degree of the six serum proteins adsorbing to the surface, the probability of binding to cell receptors and whether the liver removes the nanoparticle from circulation. Identifying the six adsorbed proteins allowed us to engineer decoy nanoparticles that prime the liver to take up fewer therapeutic nanoparticles, enabling more nanoparticles for targeting extrahepatic tissues. Elucidating the molecular interactions governing the nanoparticle journey in vivo will enable us to control nanoparticle delivery to diseased tissues. Liver macrophages are a major obstacle to extrahepatic drug delivery. This study identifies the receptor–ligand interactions that they use to capture circulating nanoparticles and leverages this understanding to engineer nanoparticles that escape macrophage uptake.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 7","pages":"914-925"},"PeriodicalIF":34.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979743","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":"Analysis of multi-drug cancer nanomedicine","authors":"Karina Benderski, Twan Lammers, Alexandros Marios Sofias","doi":"10.1038/s41565-025-01932-1","DOIUrl":"10.1038/s41565-025-01932-1","url":null,"abstract":"Multi-drug nanomedicine is gaining momentum for co-delivering more than one drug to the same site at the same time. Our analysis of 273 pre-clinical tumour growth inhibition studies shows that multi-drug nanotherapy outperforms single-drug therapy, multi-drug combination therapy, and single-drug nanotherapy by 43, 29 and 30%, respectively. Combination nanotherapy also results in the best overall survival rates, with 56% of studies demonstrating complete or partial survival, versus 20–37% for control regimens. Within the multi-drug nanomedicine groups, we analysed the effect of (co-)administration schedule and strategy, passive versus active targeting, nanocarrier material and the type of therapeutic agent. Most importantly, it was found that co-encapsulating two different drugs in the same nanoformulation reduces tumour growth by a further 19% compared with the combination of two individually encapsulated nanomedicines. We finally show that the benefit of multi-drug nanotherapy is consistently observed across different cancer types, in sensitive and resistant tumours, and in xenograft and allograft models. Altogether, this meta-analysis substantiates the value of multi-drug nanomedicine as a potent strategy to improve cancer therapy. Multi-drug nanotherapy consistently outperforms single-drug therapy, multi-drug combination therapy, and single-drug nanotherapy across different experimental settings, therapy strategies and cancer types.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 8","pages":"1163-1172"},"PeriodicalIF":34.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41565-025-01932-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979744","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}
Yakun Yi, Peng Song, Ziyi Li, Jinzhou Ju, Guixiang Sun, Qianyuan Ren, Ke Zhou, Lei Liu, Hai-Chen Wu
{"title":"Nanopore-based enzyme-linked immunosorbent assay for cancer biomarker detection","authors":"Yakun Yi, Peng Song, Ziyi Li, Jinzhou Ju, Guixiang Sun, Qianyuan Ren, Ke Zhou, Lei Liu, Hai-Chen Wu","doi":"10.1038/s41565-025-01918-z","DOIUrl":"10.1038/s41565-025-01918-z","url":null,"abstract":"Enzyme-linked immunosorbent assay (ELISA) has been widely used in cancer diagnostics due to its specificity, sensitivity and high throughput. However, conventional ELISA is semiquantitative and has an insufficiently low detection limit for applications requiring ultrahigh sensitivity. In this study, we developed an α-hemolysin-nanopore-based ELISA for detecting cancer biomarkers. After forming the immuno-sandwich complex, peptide probes carrying enzymatic cleavage sites are introduced, where they interact with enzymes conjugated to the detection antibodies within the complex. These probes generate distinct current signatures when translocated through the nanopore after enzymatic cleavage, enabling precise biomarker quantification. This approach offers a low detection limit of up to 0.03 fg ml–1 and the simultaneous detection of six biomarkers, including antigen and antibody biomarkers in blood samples. Overall, the nanopore-based ELISA demonstrates high sensitivity and multiplexing capability, making it suitable for next-generation diagnostic and point-of-care testing applications. A nanopore-based enzyme-linked immunosorbent assay is developed for the single-molecule sensing of distinct current signatures from peptide probes generated on translocation through α-hemolysin after enzymatic cleavage, enabling the multiplexed detection of biomarkers in blood samples.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 8","pages":"1079-1086"},"PeriodicalIF":34.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945953","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}
Cyrielle Fougeroux, Sven Hendrik Hagen, Louise Goksøyr, Kara-Lee Aves, Anna Kathrine Okholm, Candice Morin, Abhijeet Girish Lokras, Saahil Sandeep Baghel, Camilla Foged, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Matthijs M. Jore, Elena Ethel Vidal-Calvo, Tobias Gustavsson, Ali Salanti, Thor Grundtvig Theander, Morten Agertoug Nielsen, Willem Adriaan de Jongh, Adam Frederik Sander Bertelsen
{"title":"A modular mRNA vaccine platform encoding antigen-presenting capsid virus-like particles enhances the immunogenicity of the malaria antigen Pfs25","authors":"Cyrielle Fougeroux, Sven Hendrik Hagen, Louise Goksøyr, Kara-Lee Aves, Anna Kathrine Okholm, Candice Morin, Abhijeet Girish Lokras, Saahil Sandeep Baghel, Camilla Foged, Marga van de Vegte-Bolmer, Geert-Jan van Gemert, Matthijs M. Jore, Elena Ethel Vidal-Calvo, Tobias Gustavsson, Ali Salanti, Thor Grundtvig Theander, Morten Agertoug Nielsen, Willem Adriaan de Jongh, Adam Frederik Sander Bertelsen","doi":"10.1038/s41565-025-01889-1","DOIUrl":"10.1038/s41565-025-01889-1","url":null,"abstract":"The COVID-19 pandemic has emphasized the potential of mRNA vaccines in fighting pandemics, owing to their rapid development, strong immunogenicity and adaptability. However, a drawback is their dose-limiting reactogenicity and inability to generate durable humoral immunity. Here we introduce a modular nucleotide vaccine platform combining the advantages of genetic and capsid virus-like-particle-based vaccines. This platform allows for the display of various antigens on different capsid virus-like particles, improving the magnitude, quality and longevity of the vaccine-induced immune responses. We applied this technology to enhance the immunogenicity of the Pfs25 antigen. Immunization with lipid-nanoparticle-formulated mRNA encoding Pfs25 capsid virus-like particles resulted in higher and potentially more durable anti-Pfs25 antibody responses, along with enhanced functional activity, compared with an mRNA vaccine encoding soluble Pfs25. By improving both humoral and cellular immune responses, this approach may reduce the dose and number of administrations required for effective protection. As a result, it can improve the feasibility of both DNA- and mRNA-based vaccines targeting pandemic and endemic infectious diseases. Genetic vaccines can be quickly formulated and tested but require multiple administrations to generate a durable antibody response, as in the case of protein subunit vaccines. Here SpyTag/SpyCatcher technology is used to develop a genetic vaccine encoding antigen-displaying capsid virus-like particles to enhance the immune response against the Pfs25 malaria antigen.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 6","pages":"845-855"},"PeriodicalIF":34.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945955","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":"Better the devil you know than the devil you don’t — PEG challenges in nanomedicine","authors":"Marina A. Dobrovolskaia","doi":"10.1038/s41565-025-01925-0","DOIUrl":"10.1038/s41565-025-01925-0","url":null,"abstract":"Mass vaccination using polyethylene glycol (PEG)-containing nanoparticles during the COVID-19 pandemic has resulted in cases of adverse reactions, bringing to the fore the issue of PEG immunogenicity and reinforcing the view that this polymer should be substituted with other stealth-inducing molecules. Before considering alternatives, however, it is crucial to carry out more detailed analyses of the anti-PEG antibodies, to standardize the procedures for their detection and to better contextualize their generation within different nanoformulations, routes of administration, indication, safety and efficacy. The resulting studies could guide both the future use of PEGylated nanomedicines and the synthesis of the next generation of PEG or its alternatives.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 5","pages":"580-583"},"PeriodicalIF":34.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939967","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":"Balancing stealth and targeting to improve nanomedicine efficacy","authors":"Yi Ju, Stephen John Kent","doi":"10.1038/s41565-025-01926-z","DOIUrl":"10.1038/s41565-025-01926-z","url":null,"abstract":"Developing nanomedicines that avoid fast blood clearance while retaining targeting specificity in vivo is inherently challenging. Leveraging the individual biomolecular corona, optimizing the nature of targeting ligands and exploring alternative stealth formulations might be the key to engineering tailored nanomedicine approaches.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"20 5","pages":"576-579"},"PeriodicalIF":34.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939968","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}