Chufan Wang, Wei Feng, Jian Li, Jiaping Wang, Li Liu, Shang-hui Ye, Yuhao Zhang, Jiaxin Fu, Haiping Zheng, E. Chen, Jun Yang, Wenjun Shan, Lei Ren
{"title":"利用生物矿化病毒样颗粒的增强型纳米疫苗通过鼻到脑传递途径对胶质母细胞瘤进行有效免疫治疗","authors":"Chufan Wang, Wei Feng, Jian Li, Jiaping Wang, Li Liu, Shang-hui Ye, Yuhao Zhang, Jiaxin Fu, Haiping Zheng, E. Chen, Jun Yang, Wenjun Shan, Lei Ren","doi":"10.1021/acsnano.5c06051","DOIUrl":null,"url":null,"abstract":"Glioma, a primary malignant tumor of the central nervous system, remains a formidable challenge despite advancements in treatment. Immunotherapies hold promise, but their efficacy is hindered by the blood–brain barrier (BBB) and immunosuppressive tumor microenvironment (TME). The nose-to-brain transport pathway offers a potential solution for bypassing the BBB and avoiding systemic absorption issues. In this study, we developed a calcium phosphate (CaP)-covered nanovaccine (NV) based on hepatitis B core antigen derived virus-like particles (HBc VLPs), optimized for mucosal delivery applications. After biomineralization, this NVs exhibited enhanced mucosal adhesion and significantly higher accumulation in glioma tissue. Furthermore, by leveraging the immunogenicity of HBc VLPs and displaying a glioma-associated antigen EphA2<sub>671–679</sub> on its surface, this NVs served as both immunogen and adjuvant. They promoted significant antiglioma therapeutic efficacy and elicited robust, durable tumor suppression by increasing effective T cell infiltration, reducing regulatory T cells and M2-type tumor-associated macrophages. This innovative NV construction strategy highlights the potential of CaP-coated VLPs for enhancing nose-to-brain delivery and immunological enhancement, offering a promising avenue for the development of effective immunotherapies for glioma.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"2 1","pages":""},"PeriodicalIF":16.0000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhanced Nano-Vaccine Utilizing Biomineralized Virus-like Particles for Efficient Glioblastoma Immunotherapy via the Nose-To-Brain Delivery Pathway\",\"authors\":\"Chufan Wang, Wei Feng, Jian Li, Jiaping Wang, Li Liu, Shang-hui Ye, Yuhao Zhang, Jiaxin Fu, Haiping Zheng, E. Chen, Jun Yang, Wenjun Shan, Lei Ren\",\"doi\":\"10.1021/acsnano.5c06051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Glioma, a primary malignant tumor of the central nervous system, remains a formidable challenge despite advancements in treatment. Immunotherapies hold promise, but their efficacy is hindered by the blood–brain barrier (BBB) and immunosuppressive tumor microenvironment (TME). The nose-to-brain transport pathway offers a potential solution for bypassing the BBB and avoiding systemic absorption issues. In this study, we developed a calcium phosphate (CaP)-covered nanovaccine (NV) based on hepatitis B core antigen derived virus-like particles (HBc VLPs), optimized for mucosal delivery applications. After biomineralization, this NVs exhibited enhanced mucosal adhesion and significantly higher accumulation in glioma tissue. Furthermore, by leveraging the immunogenicity of HBc VLPs and displaying a glioma-associated antigen EphA2<sub>671–679</sub> on its surface, this NVs served as both immunogen and adjuvant. They promoted significant antiglioma therapeutic efficacy and elicited robust, durable tumor suppression by increasing effective T cell infiltration, reducing regulatory T cells and M2-type tumor-associated macrophages. This innovative NV construction strategy highlights the potential of CaP-coated VLPs for enhancing nose-to-brain delivery and immunological enhancement, offering a promising avenue for the development of effective immunotherapies for glioma.\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"2 1\",\"pages\":\"\"},\"PeriodicalIF\":16.0000,\"publicationDate\":\"2025-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://doi.org/10.1021/acsnano.5c06051\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acsnano.5c06051","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Enhanced Nano-Vaccine Utilizing Biomineralized Virus-like Particles for Efficient Glioblastoma Immunotherapy via the Nose-To-Brain Delivery Pathway
Glioma, a primary malignant tumor of the central nervous system, remains a formidable challenge despite advancements in treatment. Immunotherapies hold promise, but their efficacy is hindered by the blood–brain barrier (BBB) and immunosuppressive tumor microenvironment (TME). The nose-to-brain transport pathway offers a potential solution for bypassing the BBB and avoiding systemic absorption issues. In this study, we developed a calcium phosphate (CaP)-covered nanovaccine (NV) based on hepatitis B core antigen derived virus-like particles (HBc VLPs), optimized for mucosal delivery applications. After biomineralization, this NVs exhibited enhanced mucosal adhesion and significantly higher accumulation in glioma tissue. Furthermore, by leveraging the immunogenicity of HBc VLPs and displaying a glioma-associated antigen EphA2671–679 on its surface, this NVs served as both immunogen and adjuvant. They promoted significant antiglioma therapeutic efficacy and elicited robust, durable tumor suppression by increasing effective T cell infiltration, reducing regulatory T cells and M2-type tumor-associated macrophages. This innovative NV construction strategy highlights the potential of CaP-coated VLPs for enhancing nose-to-brain delivery and immunological enhancement, offering a promising avenue for the development of effective immunotherapies for glioma.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.