Pub Date : 2025-12-30DOI: 10.1038/s41565-025-02062-4
Application of Zn metal batteries is limited by high water activity in their electrolytes. Now, an aqueous–hydrotrope hybrid electrolyte is proposed that minimizes the water activity by confining water molecules in a hydrophilic–hydrophobic solvation sheath. This approach increases the electrochemical stability window and operating temperature range.
{"title":"Aqueous–hydrotrope hybrid electrolytes with minimized water activity for Zn metal batteries","authors":"","doi":"10.1038/s41565-025-02062-4","DOIUrl":"10.1038/s41565-025-02062-4","url":null,"abstract":"Application of Zn metal batteries is limited by high water activity in their electrolytes. Now, an aqueous–hydrotrope hybrid electrolyte is proposed that minimizes the water activity by confining water molecules in a hydrophilic–hydrophobic solvation sheath. This approach increases the electrochemical stability window and operating temperature range.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"21-22"},"PeriodicalIF":34.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863517","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 : 2025-12-30DOI: 10.1038/s41565-025-02074-0
Guoliang Liu
A tandem catalytic strategy is developed to convert polystyrene waste into a spectrum of aromatic intermediates and subsequently into a single dominant product, toluene. This tandem design enhances product selectivity and minimizes downstream separation costs.
{"title":"Catalytic conversion of polystyrene waste into toluene","authors":"Guoliang Liu","doi":"10.1038/s41565-025-02074-0","DOIUrl":"10.1038/s41565-025-02074-0","url":null,"abstract":"A tandem catalytic strategy is developed to convert polystyrene waste into a spectrum of aromatic intermediates and subsequently into a single dominant product, toluene. This tandem design enhances product selectivity and minimizes downstream separation costs.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"17-18"},"PeriodicalIF":34.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863609","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 : 2025-12-30DOI: 10.1038/s41565-025-02072-2
The multielectron CO2 reduction reaction in acid with molecular cobalt phthalocyanine catalysts is challenged by weak CO binding and competing CO2 and hydrogen adsorption. Now, a cationic, hydrophobic and aerophilic layer is shown to regulate the microenvironment around the cobalt catalytic centres, enabling 62% methanol Faradaic efficiency in strong acid.
{"title":"Microenvironment engineering for electroreduction of CO2 to methanol in strong acids","authors":"","doi":"10.1038/s41565-025-02072-2","DOIUrl":"10.1038/s41565-025-02072-2","url":null,"abstract":"The multielectron CO2 reduction reaction in acid with molecular cobalt phthalocyanine catalysts is challenged by weak CO binding and competing CO2 and hydrogen adsorption. Now, a cationic, hydrophobic and aerophilic layer is shown to regulate the microenvironment around the cobalt catalytic centres, enabling 62% methanol Faradaic efficiency in strong acid.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"19-20"},"PeriodicalIF":34.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863842","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 : 2025-12-30DOI: 10.1038/s41565-025-02053-5
Avigail Baruch Leshem, Dor Gaash, Ayala Lampel
Designed biomolecular condensates are emerging condensed-phase assemblies, initially conceived to mimic cellular biomolecular condensates for use in biology-inspired applications such as delivery and storage of biomolecules. In recent years, rational design approaches informed by supramolecular chemistry and biomolecular nanotechnology, including the use of peptide and DNA nanotechnology for building-block minimalization and site-specific interactions, have evolved rapidly, going beyond the molecular basis of cellular condensates in terms of both composition and functionality. Thus, synthetic condensates are designed from diverse molecular building blocks, including single- or multicomponent polypeptides, peptides, RNA, DNA or biopolymers; moreover, their applications are continuously evolving to encompass new nanotechnology-relevant functions including biosensing and bioadhesion, where condensates offer advantages such as responsiveness, programmability and molecular compartmentalization. In this Review, we show the main concepts behind the molecular design of synthetic condensates, from biological mimicry to purely synthetic approaches. We discuss the mechanisms that allow control and regulation of condensate properties and the remaining challenges in analysing these properties. Finally, we discuss the applications of synthetic condensates thus far, the potential in leveraging condensates as platforms for nanotechnological applications, and the remaining hurdles towards realizing this promise. We also provide an overview of the patent landscape, highlighting trends in commercial development across areas such as delivery systems, microreactors and sensing technologies. This Review presents a nanotechnology-enabled approach to the molecular design of biomolecular condensates from synthetic phase-separating building blocks, with applications in drug delivery, catalysis, cell-free protein factories, sensors and 3D bioprinting.
{"title":"Design and applications of synthetic biomolecular condensates","authors":"Avigail Baruch Leshem, Dor Gaash, Ayala Lampel","doi":"10.1038/s41565-025-02053-5","DOIUrl":"10.1038/s41565-025-02053-5","url":null,"abstract":"Designed biomolecular condensates are emerging condensed-phase assemblies, initially conceived to mimic cellular biomolecular condensates for use in biology-inspired applications such as delivery and storage of biomolecules. In recent years, rational design approaches informed by supramolecular chemistry and biomolecular nanotechnology, including the use of peptide and DNA nanotechnology for building-block minimalization and site-specific interactions, have evolved rapidly, going beyond the molecular basis of cellular condensates in terms of both composition and functionality. Thus, synthetic condensates are designed from diverse molecular building blocks, including single- or multicomponent polypeptides, peptides, RNA, DNA or biopolymers; moreover, their applications are continuously evolving to encompass new nanotechnology-relevant functions including biosensing and bioadhesion, where condensates offer advantages such as responsiveness, programmability and molecular compartmentalization. In this Review, we show the main concepts behind the molecular design of synthetic condensates, from biological mimicry to purely synthetic approaches. We discuss the mechanisms that allow control and regulation of condensate properties and the remaining challenges in analysing these properties. Finally, we discuss the applications of synthetic condensates thus far, the potential in leveraging condensates as platforms for nanotechnological applications, and the remaining hurdles towards realizing this promise. We also provide an overview of the patent landscape, highlighting trends in commercial development across areas such as delivery systems, microreactors and sensing technologies. This Review presents a nanotechnology-enabled approach to the molecular design of biomolecular condensates from synthetic phase-separating building blocks, with applications in drug delivery, catalysis, cell-free protein factories, sensors and 3D bioprinting.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"39-52"},"PeriodicalIF":34.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863797","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 : 2025-12-29DOI: 10.1038/s41565-025-02093-x
Friedrich Striggow, Pallavi Jha, Ripla Arora, Mariana Medina-Sánchez
Technological developments in reproductive medicine, driven by the convergence of micro-robotics and nanosensors, along with decision-making aided by artificial intelligence, are enabling precise manipulation, gamete selection, embryo assessment and personalized treatment. These disruptive advances could lead to fully automated in vitro fertilization workflows. However, clinical implementation will need to address various technical, biological and ethical challenges to ensure safer and more effective fertility solutions.
{"title":"Navigating the future of assisted reproductive technology with micro-robotics, nanobiosensors and artificial intelligence","authors":"Friedrich Striggow, Pallavi Jha, Ripla Arora, Mariana Medina-Sánchez","doi":"10.1038/s41565-025-02093-x","DOIUrl":"10.1038/s41565-025-02093-x","url":null,"abstract":"Technological developments in reproductive medicine, driven by the convergence of micro-robotics and nanosensors, along with decision-making aided by artificial intelligence, are enabling precise manipulation, gamete selection, embryo assessment and personalized treatment. These disruptive advances could lead to fully automated in vitro fertilization workflows. However, clinical implementation will need to address various technical, biological and ethical challenges to ensure safer and more effective fertility solutions.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"2-5"},"PeriodicalIF":34.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857280","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 : 2025-12-29DOI: 10.1038/s41565-025-02083-z
Gabriel De Leon, Li Zhang, Nabil A. Siddiqui, Nada Naguib, Feng Chen, Reethi Padmanabhan, Tuo Zhang, Sebastien Monette, Fabio Socciarelli, Rachel Lee, Miles Pourbaghi, Thomas P. Quinn, Michael Overholtzer, Taha Merghoub, Ulrich Wiesner, Jedd D. Wolchok, Michelle S. Bradbury
Despite the considerable success of clinically approved immune-based therapies for treating advanced melanoma, a significant fraction of patients are not responsive owing to mechanisms engaged by the tumour to evade the immune system. Here we report the surprising finding that a clinically validated and tunable self-therapeutic ultrasmall silica nanoparticle prolongs survival in a highly resistant melanoma model in combination with interleukin-6 and PD-L1 inhibition through activation of the stimulator of interferon genes/interleukin-6/PD-L1 axis and reprogramming of the tumour microenvironment towards a pro-inflammatory phenotype. In a murine model, induction of significant cytotoxic and antitumour inflammatory responses leads to differential activation of immune cell populations in a CD8-dependent manner via type I/II interferon pathways after systemic particle injection. Importantly, these immunostimulatory responses accompany significant reductions in cell populations and receptors driving suppressive activities. Mechanistic insights highlight the potential clinical utility of this platform to maximize antitumour immunity and efficacy by subverting suppressive components in the tumour microenvironment. An ultrasmall particle adjuvant therapy reprogrammes the tumour microenvironment of a resistant melanoma to a pro-inflammatory state, enhances antitumour immunity and synergizes with immune checkpoint inhibitors to prolong survival in murine models.
{"title":"An ultrasmall core–shell silica nanoparticle improves antitumour immunity and survival by remodelling suppressive melanoma microenvironments","authors":"Gabriel De Leon, Li Zhang, Nabil A. Siddiqui, Nada Naguib, Feng Chen, Reethi Padmanabhan, Tuo Zhang, Sebastien Monette, Fabio Socciarelli, Rachel Lee, Miles Pourbaghi, Thomas P. Quinn, Michael Overholtzer, Taha Merghoub, Ulrich Wiesner, Jedd D. Wolchok, Michelle S. Bradbury","doi":"10.1038/s41565-025-02083-z","DOIUrl":"10.1038/s41565-025-02083-z","url":null,"abstract":"Despite the considerable success of clinically approved immune-based therapies for treating advanced melanoma, a significant fraction of patients are not responsive owing to mechanisms engaged by the tumour to evade the immune system. Here we report the surprising finding that a clinically validated and tunable self-therapeutic ultrasmall silica nanoparticle prolongs survival in a highly resistant melanoma model in combination with interleukin-6 and PD-L1 inhibition through activation of the stimulator of interferon genes/interleukin-6/PD-L1 axis and reprogramming of the tumour microenvironment towards a pro-inflammatory phenotype. In a murine model, induction of significant cytotoxic and antitumour inflammatory responses leads to differential activation of immune cell populations in a CD8-dependent manner via type I/II interferon pathways after systemic particle injection. Importantly, these immunostimulatory responses accompany significant reductions in cell populations and receptors driving suppressive activities. Mechanistic insights highlight the potential clinical utility of this platform to maximize antitumour immunity and efficacy by subverting suppressive components in the tumour microenvironment. An ultrasmall particle adjuvant therapy reprogrammes the tumour microenvironment of a resistant melanoma to a pro-inflammatory state, enhances antitumour immunity and synergizes with immune checkpoint inhibitors to prolong survival in murine models.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 2","pages":"311-322"},"PeriodicalIF":34.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41565-025-02083-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857287","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 : 2025-12-29DOI: 10.1038/s41565-025-02082-0
Xiao Chen, Dongyang Zhou, Jian Wang, Han Liu, Hao Zhang, Zhen Geng, Guangchao Wang, Hao Shen, Yuanwei Zhang, Zuhao Li, Dongliang Wang, Xiaoxiang Ren, Xiuhui Wang, Ke Xu, Chongru He, Long Bai, Yan Wei, Xiaoyuan Chen, Jiacan Su
Osteoarthritis (OA) affects a large population worldwide, causing chronic pain, functional decline, and increased personal and societal medical costs. A major challenge in developing disease-modifying OA drugs (DMOADs) is the inefficient delivery to diseased chondrocytes. Here we synthesize a viral glycoprotein-mimicking peptide (CMP) containing a type II collagen-adhesive motif and a matrix metalloproteinase-13-activated cell-penetrating peptide sequence. The CMP peptide was conjugated to small-sized micelles loaded with the model drug IOX4, enabling the micelles to adhere to cartilage and chondrocyte surfaces through collagen binding and achieve proteinase-induced selective uptake by diseased chondrocytes. In an OA mouse model, our micelles demonstrated prolonged joint retention and exhibited a higher uptake by diseased chondrocytes compared with unmodified micelles and normal chondrocytes, respectively. In both OA mice and a clinically relevant OA sheep model, our system maintained metabolic homeostasis in cartilage, attenuating OA pathological changes and improving symptoms without causing additional toxicity. These findings suggest that our nanoformulation is a promising DMOAD candidate and provides an efficient delivery strategy for other potential DMOADs targeting intracellular sites of diseased chondrocytes. A virus-mimicking micelle selectively delivers drugs to diseased chondrocytes in osteoarthritis, significantly alleviating disease progression in mouse and sheep models.
{"title":"Viral glycoprotein-mimicking peptide-functionalized micelles promote drug delivery to diseased chondrocytes for osteoarthritis alleviation","authors":"Xiao Chen, Dongyang Zhou, Jian Wang, Han Liu, Hao Zhang, Zhen Geng, Guangchao Wang, Hao Shen, Yuanwei Zhang, Zuhao Li, Dongliang Wang, Xiaoxiang Ren, Xiuhui Wang, Ke Xu, Chongru He, Long Bai, Yan Wei, Xiaoyuan Chen, Jiacan Su","doi":"10.1038/s41565-025-02082-0","DOIUrl":"10.1038/s41565-025-02082-0","url":null,"abstract":"Osteoarthritis (OA) affects a large population worldwide, causing chronic pain, functional decline, and increased personal and societal medical costs. A major challenge in developing disease-modifying OA drugs (DMOADs) is the inefficient delivery to diseased chondrocytes. Here we synthesize a viral glycoprotein-mimicking peptide (CMP) containing a type II collagen-adhesive motif and a matrix metalloproteinase-13-activated cell-penetrating peptide sequence. The CMP peptide was conjugated to small-sized micelles loaded with the model drug IOX4, enabling the micelles to adhere to cartilage and chondrocyte surfaces through collagen binding and achieve proteinase-induced selective uptake by diseased chondrocytes. In an OA mouse model, our micelles demonstrated prolonged joint retention and exhibited a higher uptake by diseased chondrocytes compared with unmodified micelles and normal chondrocytes, respectively. In both OA mice and a clinically relevant OA sheep model, our system maintained metabolic homeostasis in cartilage, attenuating OA pathological changes and improving symptoms without causing additional toxicity. These findings suggest that our nanoformulation is a promising DMOAD candidate and provides an efficient delivery strategy for other potential DMOADs targeting intracellular sites of diseased chondrocytes. A virus-mimicking micelle selectively delivers drugs to diseased chondrocytes in osteoarthritis, significantly alleviating disease progression in mouse and sheep models.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 2","pages":"300-310"},"PeriodicalIF":34.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857335","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 : 2025-12-26DOI: 10.1038/s41565-025-02068-y
Florian Dirnberger, Sophia Terres, Zakhar A. Iakovlev, Kseniia Mosina, Zdenek Sofer, Akashdeep Kamra, Mikhail M. Glazov, Alexey Chernikov
Optical quasiparticles called magnetic excitons recently emerged in magnetic van der Waals materials. Akin to the highly effective strategies developed for electrons, the strong interactions of these excitons with the spin degree of freedom may provide innovative solutions for long-standing challenges in optics, such as steering the flow of energy and information. Here we demonstrate the transport of excitons by spin excitations in the van der Waals antiferromagnetic semiconductor CrSBr. Our observations reveal ultrafast, nearly isotropic exciton propagation, substantially enhanced at the Néel temperature, transient contraction and expansion of exciton clouds at low temperatures and superdiffusive behaviour in bilayer samples. These signatures largely defy description by commonly known exciton transport mechanisms. Instead, we attribute them to magnon currents induced by laser excitation. We propose that the drag forces exerted by these currents can effectively imprint characteristic properties of spin excitations onto the motion of excitons. The universal nature of the underlying magnon–exciton scattering promises the driving of excitons by magnons in other magnetic semiconductors and even in non-magnetic materials by proximity in heterostructures, merging the rich physics of magnetotransport with optics and photonics. Exciton propagation in CrSBr is strongly influenced by magnetic properties, particularly peaking at the Néel temperature. Its transport is not governed by classical diffusion but rather by an interaction with the spin degree of freedom, specifically through a magnon–exciton drag effect.
{"title":"Exciton transport driven by spin excitations in an antiferromagnet","authors":"Florian Dirnberger, Sophia Terres, Zakhar A. Iakovlev, Kseniia Mosina, Zdenek Sofer, Akashdeep Kamra, Mikhail M. Glazov, Alexey Chernikov","doi":"10.1038/s41565-025-02068-y","DOIUrl":"10.1038/s41565-025-02068-y","url":null,"abstract":"Optical quasiparticles called magnetic excitons recently emerged in magnetic van der Waals materials. Akin to the highly effective strategies developed for electrons, the strong interactions of these excitons with the spin degree of freedom may provide innovative solutions for long-standing challenges in optics, such as steering the flow of energy and information. Here we demonstrate the transport of excitons by spin excitations in the van der Waals antiferromagnetic semiconductor CrSBr. Our observations reveal ultrafast, nearly isotropic exciton propagation, substantially enhanced at the Néel temperature, transient contraction and expansion of exciton clouds at low temperatures and superdiffusive behaviour in bilayer samples. These signatures largely defy description by commonly known exciton transport mechanisms. Instead, we attribute them to magnon currents induced by laser excitation. We propose that the drag forces exerted by these currents can effectively imprint characteristic properties of spin excitations onto the motion of excitons. The universal nature of the underlying magnon–exciton scattering promises the driving of excitons by magnons in other magnetic semiconductors and even in non-magnetic materials by proximity in heterostructures, merging the rich physics of magnetotransport with optics and photonics. Exciton propagation in CrSBr is strongly influenced by magnetic properties, particularly peaking at the Néel temperature. Its transport is not governed by classical diffusion but rather by an interaction with the spin degree of freedom, specifically through a magnon–exciton drag effect.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"65-70"},"PeriodicalIF":34.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41565-025-02068-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843888","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}
Glioblastoma stem cells (GSCs), which exhibit resistance to multiple treatments, are a prominent driver of postoperative glioblastoma (GBM) relapse. Reducing the GSC population holds promise in GBM therapy but remains challenging due to the difficulty in coordinating the complex cytokine signalling programs and extracellular matrix characteristics that induce GSC expansion. Here we develop a biohybrid chiral hydrogel that allows intracavity implantation after GBM surgical debulking to comprehensively regulate GSC stemness, enhancing postoperative therapy. The hydrogel encapsulates GSC-membrane-coated nanoparticles that serve as potent decoys to broadly neutralize GSC-targeted pro-stemness and chemotaxis cytokines, allowing functional blocking and hydrogel infiltration of GSCs. Moreover, we showed that the D-chiral biohybrid hydrogel, in contrast to its L- and DL-chiral counterparts, further diminished the GSC stemness phenotype via D-chiral-geometry-regulated mechanotransduction pathways. In three orthotopic intracranial GBM models, the multi-pronged inhibition of GSC stemness enhanced gold-nanocluster-based hydrogel-scaffold-sensitized radioimmunotherapy, enabling the suppression of GBM relapse post-resection. This integrated regulation of biochemical and biophysical cues shows the potential for treating cancer-stem-cell-enriched malignancies. A biohybrid chiral hydrogel combining cell-membrane-coated nanoparticles with a D-chiral matrix reduces tumour stemness via biochemical and biophysical regulation, boosting radioimmunotherapy and preventing postoperative glioblastoma recurrence.
{"title":"A biohybrid chiral hydrogel enhances preclinical postoperative glioblastoma therapy by multi-pronged inhibition of tumour stemness","authors":"Tingting Cui, Sixue Chen, Siqin Liu, Xuegang Niu, Jun Wang, Rujiang Ao, Huilan Cai, Hongwei Huang, Meili Yu, Shanshan Peng, Xiaoyuan Chen, Lisen Lin","doi":"10.1038/s41565-025-02064-2","DOIUrl":"10.1038/s41565-025-02064-2","url":null,"abstract":"Glioblastoma stem cells (GSCs), which exhibit resistance to multiple treatments, are a prominent driver of postoperative glioblastoma (GBM) relapse. Reducing the GSC population holds promise in GBM therapy but remains challenging due to the difficulty in coordinating the complex cytokine signalling programs and extracellular matrix characteristics that induce GSC expansion. Here we develop a biohybrid chiral hydrogel that allows intracavity implantation after GBM surgical debulking to comprehensively regulate GSC stemness, enhancing postoperative therapy. The hydrogel encapsulates GSC-membrane-coated nanoparticles that serve as potent decoys to broadly neutralize GSC-targeted pro-stemness and chemotaxis cytokines, allowing functional blocking and hydrogel infiltration of GSCs. Moreover, we showed that the D-chiral biohybrid hydrogel, in contrast to its L- and DL-chiral counterparts, further diminished the GSC stemness phenotype via D-chiral-geometry-regulated mechanotransduction pathways. In three orthotopic intracranial GBM models, the multi-pronged inhibition of GSC stemness enhanced gold-nanocluster-based hydrogel-scaffold-sensitized radioimmunotherapy, enabling the suppression of GBM relapse post-resection. This integrated regulation of biochemical and biophysical cues shows the potential for treating cancer-stem-cell-enriched malignancies. A biohybrid chiral hydrogel combining cell-membrane-coated nanoparticles with a D-chiral matrix reduces tumour stemness via biochemical and biophysical regulation, boosting radioimmunotherapy and preventing postoperative glioblastoma recurrence.","PeriodicalId":18915,"journal":{"name":"Nature nanotechnology","volume":"21 1","pages":"140-155"},"PeriodicalIF":34.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843849","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：