Biomaterials最新文献

{"title":"Nanoparticles with reprogramming of mitochondrial respiratory chain complex and epigenetic modifications functions for osteoporosis treatment","authors":"Yiping Liu ,&nbsp;Liangjing Xin ,&nbsp;Si Wang,&nbsp;Junlong Tan,&nbsp;Xingyu Zhu,&nbsp;Xu Chen,&nbsp;Jinlin Song,&nbsp;Tao Chen,&nbsp;Qiming Zhai","doi":"10.1016/j.biomaterials.2025.123468","DOIUrl":"10.1016/j.biomaterials.2025.123468","url":null,"abstract":"<div><div>Current therapies primarily focusing on osteoporosis often fail to address the root relationship between metabolic reprogramming and epigenetic modification alterations. Developing an efficient therapeutic approach with dual-pronged functionality for the treatment of osteoporosis represents a noteworthy challenge. Herein, samples from humans and rats with osteoporosis presented in this study underscore the correlation between mitochondrial metabolism, epigenetic modifications, and osteoporotic bone loss. Inspired by this, we focus on designing a nano-therapy that serves as a strategy, targeting both the maintenance of metabolic homeostasis and the modulation of epigenetic modifications, thereby achieving a dual-functional effect in the treatment of osteoporosis. Accordingly, 4-octyl itaconate (OI), which exhibits immunometabolic activity and regulates epigenetic modifications, was encapsulated within mesoporous silica (MSN) and further modified with a cerium ion-coordinated tannic acid (Ce-TA) supramolecular network on its surface for boosting antioxidant properties. In brief, MSN-OI@Ce-TA (MOCT NPs) exhibit synergistically enhanced antioxidant capabilities in pro-inflammatory macrophages and alleviates osteoporotic bone loss by restoring mitochondrial respiratory chain complex function, remodeling DNA and histone modifications, and thereby restoring osteoimmune homeostasis. Overall, these findings highlight the compelling dual treatment mechanisms of MOCT NPs, providing a theoretical basis for the management of osteoporosis.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123468"},"PeriodicalIF":12.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon-based nanozymes in cancer therapy: Current trends and future prospects","authors":"lin Zhan ,&nbsp;Huan Zhou ,&nbsp;Jin Lu ,&nbsp;Xuelian Yin","doi":"10.1016/j.biomaterials.2025.123465","DOIUrl":"10.1016/j.biomaterials.2025.123465","url":null,"abstract":"<div><div>Cancer has become a major global health challenge, and current treatment modalities, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, all have inherent limitations. In recent years, nanotechnology, particularly carbon-based nanozymes, has emerged as a promising approach in cancer therapy. Carbon-based nanozymes, as a novel class of catalysts, offer excellent biocompatibility, low toxicity, and good stability. They can catalyze reactions that generate reactive oxygen species (ROS), which directly kill cancer cells or enhance the bioavailability of therapeutic agents, thereby improving treatment efficacy. Compared to conventional nanozymes, carbon-based nanozymes are easier to synthesize, more versatile, and exhibit greater durability, making them highly promising for cancer therapy. This review aims to provide a comprehensive overview of the classifications, catalytic mechanisms, and applications of carbon-based nanozymes in cancer therapy, with a focus on catalytic and multimodal treatment strategies. It highlights the unique advantages of carbon-based nanozymes and discusses the current state of research in this field. By synthesizing the available literature, this review offers valuable insights for researchers and encourages further exploration of carbon-based nanozymes in cancer treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123465"},"PeriodicalIF":12.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomaterial-based therapeutic strategies for inflammatory bowel disease","authors":"Wei Sun ,&nbsp;Zhibo Li ,&nbsp;Xiaohao Zhang ,&nbsp;Qiang Luo ,&nbsp;Lijuan Wei ,&nbsp;Chunsheng Xiao","doi":"10.1016/j.biomaterials.2025.123462","DOIUrl":"10.1016/j.biomaterials.2025.123462","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a chronic, challenging condition characterized by epithelial barrier disruption, immune dysregulation, and alterations in gut microbiota, leading to symptoms such as abdominal pain, diarrhea, and weight loss, affecting millions of patients worldwide. The etiology and pathogenesis of IBD are multifactorial, involving a combination of genetic factors, environmental influences, microbial dysbiosis, and other elements. Current treatments for IBD include aminosalicylates, antibiotics, corticosteroids, and immunosuppressants, all aimed at reducing inflammation and achieving clinical remission. However, the frequent and prolonged use of these medications results in significant adverse effects, including joint pain, diabetes, and osteoporosis. Therefore, targeting drug delivery to affected areas, extending the duration of drug action, and minimizing systemic exposure are crucial for effective IBD management. Emerging strategies that target excess reactive oxygen species, modulate local inflammation, and restore gut microbiota homeostasis show promise for improving IBD treatment. Biomaterials have demonstrated considerable potential in precisely delivering therapeutic agents selectively to inflamed tissues, thereby minimizing off-target effects and improving efficacy. This review highlights recent advancements in biomaterials for IBD treatment and explores future directions and challenges in their clinical application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123462"},"PeriodicalIF":12.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pH-responsive guanidino-based covalent organic framework nanodrugs for enhanced neuroprotection against subarachnoid hemorrhage by targeting NLRP3 inflammasome","authors":"Li Yang ,&nbsp;Si Zhang ,&nbsp;Qinghua Luo ,&nbsp;Hongxing Shu ,&nbsp;Wentao Xu ,&nbsp;Xinyi Zhu ,&nbsp;Ping Hu ,&nbsp;Yanze Wu ,&nbsp;Lei Shu ,&nbsp;Junzhe Liu ,&nbsp;Min Luo ,&nbsp;Wei Tu ,&nbsp;Haocheng Liu ,&nbsp;Shigang Lv ,&nbsp;Li Wang ,&nbsp;Xingen Zhu ,&nbsp;Wenping Zhu ,&nbsp;Tengfeng Yan","doi":"10.1016/j.biomaterials.2025.123467","DOIUrl":"10.1016/j.biomaterials.2025.123467","url":null,"abstract":"<div><div>Subarachnoid hemorrhage (SAH) represents a severe subtype of stroke, distinguished by its substantial mortality and morbidity rates. It initiates a series of harmful physiological responses, such as increased intracranial pressure, cerebral edema, and neuroinflammation. Pyroptosis, a form of cell death dependent on caspase-1, plays a crucial role in the inflammatory processes following SAH. Recent research indicated that the inhibition of the NLRP3 inflammasome is regarded as a promising therapeutic strategy for mitigating inflammatory responses. Bindarit, a β-blocker with anti-inflammatory properties, has demonstrated potential in mitigating NLRP3-mediated pyroptosis. Nevertheless, its clinical application is limited by its short half-life and inadequate penetration of the blood-brain barrier (BBB). To address these limitations, a novel pH-responsive erythrocyte membrane-biomimetic guanidino-based covalent organic framework (COF) nanocarrier, designated as B@COF_DT-R, has been developed to encapsulate bindarit. This nanocarrier is specifically engineered to enhance drug delivery across the BBB and target the NLRP3/Caspase-1/GSDMD axis, thereby inhibiting neuronal pyroptosis in vitro and vivo. The development of B@COF_DT-R constitutes a substantial advancement in the treatment of SAH. Through the enhancement of drug delivery mechanisms and the targeted modulation of critical inflammatory pathways, this nanocarrier holds the potential to significantly improve therapeutic outcomes for patients suffering from SAH.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123467"},"PeriodicalIF":12.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient cancer immunogenetherapy by tumor cell lysate modified mRNA formulation","authors":"Jieping Wu ,&nbsp;Xizi Fu ,&nbsp;Xiaohua Chen ,&nbsp;Ming Shuai ,&nbsp;Mohan Liu ,&nbsp;Jingmei Li ,&nbsp;Yan Gao ,&nbsp;Jin Zhang ,&nbsp;Yi Zhun Zhu ,&nbsp;Na Zhou ,&nbsp;Ke Men ,&nbsp;Xingmei Duan","doi":"10.1016/j.biomaterials.2025.123466","DOIUrl":"10.1016/j.biomaterials.2025.123466","url":null,"abstract":"<div><div>mRNA-based gene therapy has an important role in cancer therapy. Intensive attention has been paid to investigate mRNA-delivery systems with high efficiency of delivery, but few studies have explored the immunotherapeutic capacity of the delivery vector. A tumor cell lysate represents an ideal resource for constructing advanced mRNA-delivery systems with immunostimulatory potential. However, the limited room of mRNA vectors and the complex composition of the cancer cell lysate are obstacles to their combined function. In this study, we present a novel tumor cell lysate-based mRNA delivery system, TLSV/IL-17A (tumor cell lysate vehicles carrying interleukin (IL)-17A-coded mRNA). TLSV demonstrates high mRNA delivery efficiency in both dendritic cells (DCs) and tumor cells. It triggers a robust anti-cancer immune response by specifically activating plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells. By loading IL-17A mRNA, the TLSV/IL-17A effectively inhibits multiple colon cancer models. Our results demonstrate the therapeutic potential of TLSV system in tumor immunogenetherapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123466"},"PeriodicalIF":12.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biomaterial-based platform of pancreatic cancer reveals kallikrein-related peptidase 6 (KLK6) as a mediator of neutrophil recruitment and immunosuppression","authors":"Verena J. Kast ,&nbsp;Sandra Hauser ,&nbsp;Ali Nadernezhad ,&nbsp;Dagmar Pette ,&nbsp;Manfred F. Maitz ,&nbsp;Andreas Petzold ,&nbsp;Andreas Dahl ,&nbsp;Michael Seifert ,&nbsp;Katja Eubler ,&nbsp;Artur Mayerhofer ,&nbsp;Jens Pietzsch ,&nbsp;Franziska Baenke ,&nbsp;Daniel E. Stange ,&nbsp;Carsten Werner ,&nbsp;Daniela Loessner","doi":"10.1016/j.biomaterials.2025.123456","DOIUrl":"10.1016/j.biomaterials.2025.123456","url":null,"abstract":"<div><div>In pancreatic cancer, response to treatment is impaired by the tumor microenvironment (TME), forming a desmoplastic barrier. However, experimental 3D models that adequately model the pancreatic TME are still missing. Here, we employ a matrix metalloproteinase (MMP)-degradable star-shaped poly(ethylene glycol) (star-PEG)-heparin hydrogel matrix to replicate pathophysiological features of the pancreatic environment and investigate the role of the tumor-associated protease kallikrein-related peptidase 6 (KLK6) in 3D. Coupled with CRISPR/Cas9, we found that KLK6 promotes cancer growth. RNA sequencing revealed that KLK6 impairs genes associated with antigen presentation and neutrophil recruitment, all major immune suppressors in pancreatic cancer. In patients, KLK6 expression correlated with neutrophil-recruiting chemokines. Neutrophil recruitment was recapitulated <em>in vitro,</em> which was lower in the absence of KLK6. Treatment of neutrophils with cell-conditioned KLK6 knockout medium reduced the immunosuppressive phenotype, indicated by decreased <em>arginase 1</em> (<em>Arg1</em>) expression. KLK6 also impacted genes associated with immune checkpoint inhibition and decreased cell responses to anti-PD-1 checkpoint blockade <em>in vitro</em>. Our study identified KLK6 as a drug target as it regulates neutrophil recruitment, immunosuppression, and cell responses to anti-PD-1 therapy in a biomaterial-based disease model.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123456"},"PeriodicalIF":12.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo brown adipogenic reprogramming induced by a small molecule cocktail","authors":"Shrute Kannappan ,&nbsp;Yuna Kim ,&nbsp;Debojyoti De ,&nbsp;Rehna Paula Ginting ,&nbsp;Hyeon-Gung Yang ,&nbsp;Kyungmin Kim ,&nbsp;Varun Bansal ,&nbsp;Su Myung Jung ,&nbsp;Jee-Yin Ahn ,&nbsp;Sung Hee Um ,&nbsp;Min-Woo Lee ,&nbsp;Jung Heon Lee ,&nbsp;Kyeong Kyu Kim","doi":"10.1016/j.biomaterials.2025.123463","DOIUrl":"10.1016/j.biomaterials.2025.123463","url":null,"abstract":"<div><div>Research on the browning of adipocytes has been increasing in recent years owing to the prevalence of lifestyle diseases such as obesity and diabetes. Accumulation of brown fat enhances energy expenditure and could be a strategy to fight obesity. While approaches to induce browning in animals for therapeutic purposes have been tested, clinically applicable options are limited. Here, we propose chemically induced <em>in vivo</em> brown adipogenic reprogramming for the therapeutic application of brown adipocytes. By phenotypic screening, we identified a novel combination of two small molecules, SB431542 (SB) and NKH477 (NK), a TGFβ inhibitor and a cAMP activator, respectively, that could reprogram mouse embryonic fibroblasts (MEFs) to adipocyte-like cells with brown/beige adipocyte properties. We demonstrated that the expression of both <em>Pparγ</em> and <em>Cebpβ</em> via TGFβ inhibition and cAMP activation is essential for the increased activation of UCP1 due to the synergistic effects of SB and NK combination (SBNK) on adipogenesis. We further demonstrated the potential clinical application of this <em>in vivo</em> brown adipogenic reprogramming by showing that high-fat diet (HFD)--fed mice treated intraperitoneally with the SBNK exhibited enhanced browning capacity and were protected from HFD-induced impairment of glucose metabolism. Finally, microneedle patches embedded with SBNK-loaded nanoparticles were applied to the mice's skin around subcutaneous white adipose tissue to test the efficacy of local delivery, which also showed a browning effect. Taken together, a novel combination of small molecules that synergistically induced browning with far-reaching translatable therapeutic potentials was developed in this study.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123463"},"PeriodicalIF":12.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-specific ferroptosis targeting tumors while sparing immune cells","authors":"Yuanlin Wang ,&nbsp;Yaqian Han ,&nbsp;Jingshi Li ,&nbsp;Zhaotong Wang ,&nbsp;Kai Li ,&nbsp;Tiancheng Bai ,&nbsp;Lei Wang ,&nbsp;Ye Sun ,&nbsp;Chunying Chen ,&nbsp;Miao Yu","doi":"10.1016/j.biomaterials.2025.123457","DOIUrl":"10.1016/j.biomaterials.2025.123457","url":null,"abstract":"<div><div>Ferroptosis serves as a pivotal mechanism in diverse clinical chemotherapeutics and physiological processes, profoundly impacting tumor metabolism and the tumor microenvironment. Recently, the immunosuppression induced by ferroptosis has raised major concerns regarding tumor recurrence upon ferroptosis-based antitumor therapies. However, due to the lack of cell specificity, the antitumor and immunosuppressive effects in ferroptosis are inherently intertwined. Herein, we address the conflicting challenges between immunosuppression and antitumor efficacy in ferroptosis-based therapy by enabling cell-specific ferroptosis, thereby targeting tumors while sparing immune cells. By employing a specially designed nanoagent, <em>i.e.</em>, ferrous selenide half-shell-covered gold, we induce notable upregulation of glutathione peroxidase 4 (GPX4) and downregulation of prostaglandin E2, leading to an increase in CD⁴⁺ and CD⁸⁺ T cell populations and intense antitumor immune responses. Despite the elevated level of GPX4, significant tumor cell ferroptosis is achieved, which is further promoted by the agent's photothermal and photocatalytic effects. Consequently, long-term immunological memory is established, yielding a long-lasting and recurrence-free antitumor efficacy spanning at least 200 days post-treatment. This work unlocks an avenue to balance immunosuppression reversal with tumor inhibition in ferroptosis-based therapies, providing promising prospects for antitumor therapies facing immunological hurdles in the tumor microenvironment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"323 ","pages":"Article 123457"},"PeriodicalIF":12.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered macroporous gelatin scaffolds enhance lymph node fibroblastic reticular cell identity and enable diabetogenic T cell immunomodulation","authors":"Leonor N. Teles ,&nbsp;Logan A. Beatty ,&nbsp;Ana V. Hernandez ,&nbsp;Marvin A. Mendoza Jr. ,&nbsp;Zachary M. Wilkes ,&nbsp;Vivien P. Dominick ,&nbsp;Michelle T. Argy Telias ,&nbsp;Benjamin Miller ,&nbsp;Chun-Yuh Huang ,&nbsp;Camillo Bechi Genzano ,&nbsp;Fotios M. Andreopoulos ,&nbsp;Edward A. Dauer ,&nbsp;Remi J. Creusot ,&nbsp;Alice A. Tomei","doi":"10.1016/j.biomaterials.2025.123460","DOIUrl":"10.1016/j.biomaterials.2025.123460","url":null,"abstract":"<div><div>Current treatments for autoimmune diseases like Type 1 Diabetes (T1D) carry significant risks because they lack tissue specificity. A promising strategy is to achieve persistent presentation of relevant antigens (Ags) in non-inflamed sites by tolerogenic Ag-presenting cells (APCs) like fibroblastic reticular cells (FRCs). FRCs build lymph node (LN) reticula and act as immunomodulatory non-professional APCs. However, their therapeutic potential for Ag-specific immunomodulation for T1D remains unexplored. We engineered 3D FRC-based reticula using freeze-dried macroporous gelatin scaffolds with customizable pore diameters (small: &lt;50 μm, medium: &lt;200 μm, large: &lt;300 μm) to evaluate FRC phenotype and FRC-T cell interactions, leveraging FRCs’ ability to build dynamic LN reticula that expand and contract during inflammation. Our scaffolds promoted FRC viability, reticular formation, FRC phenotypic marker expression, and extracellular matrix secretion compared to 2D culture. GFP-Luciferase fusion (GLF)-expressing FRCs subcutaneously implanted in our scaffolds survived for at least 21 days regardless of pore size. Implantation in the vascularized fat pad led to graft rejection by day 14 in pre-diabetic NOD mice but not in immunodeficient NODscid. Our scaffolds outperformed clinically-used biologic gels, demonstrated the limitations of the NOD mouse model in longitudinal imaging of GLF⁺ cell survival, and validated our scaffold-based FRC delivery approach for future therapeutic applications. Co-culture of T cells in scaffolds with FRCs presenting T1D Ags enabled Ag-specific T cell engagement with reduced cytotoxic and increased anergic and regulatory phenotypes. Our results validate the use of macroporous gelatin scaffolds to enhance FRC phenotypic markers, <em>in vivo</em> survival, and diabetogenic cell immunomodulation <em>in vitro</em>.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123460"},"PeriodicalIF":12.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The minimalist epigenetic nano-adjuvant gMSN reprograms dendritic cells to enhance the mucosal immune response of oral vaccines","authors":"Wen Guo ,&nbsp;Zhiqi Wang ,&nbsp;Rubing Xue ,&nbsp;Xinyue Zhang ,&nbsp;Qinfu Zhao ,&nbsp;Yikun Gao ,&nbsp;Siling Wang ,&nbsp;Yuling Mao","doi":"10.1016/j.biomaterials.2025.123459","DOIUrl":"10.1016/j.biomaterials.2025.123459","url":null,"abstract":"<div><div>Weak response is the bottleneck for subunit prophylactic vaccines to trigger efficient immunization. The emergence of highly effective adjuvants will revolutionize. Considering that genomic epigenetic reprogramming plays an important role in the immune response, we herein present an minimalist epigenetic nano-adjuvant gMSN constructed of β-glucan-modified functional mesoporous silica (MSN), which we term as OVA/gMSN after loaded with the model antigen ovalbumin (OVA). Oral administration of OVA/gMSN ensures that enough antigen reach dendritic cells (DCs) in intestinal mucosal lymphoid follicles via intestinal M cells while relying on gMSN to exhibit good adjuvant properties to trigger an effective systemic co-mucosal immune response. gMSN upregulates genes associated with aerobic glycolysis, promoting metabolic reprogramming in DCs and enhancing the expression of genes related to DC activation, cross-presentation, maturation, and migration. Simultaneously, it increases the accumulation of key epigenetic markers H3K27ac, H3K4me1, and H3K4me3. ATAC-seq results reveal enhanced chromatin accessibility of key immune genes, such as Il2rα1, Il18r1, and Cd83, in gMSN-treated DCs. This integrative molecular mechanism demonstrates that gMSN induces epigenomic remodeling in DCs after oral administration, showcasing the potential of combining epigenetic adjuvants and nanotechnology in oral vaccine design, and providing new directions and a theoretical basis for vaccine adjuvant development.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123459"},"PeriodicalIF":12.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}