Cara S Smith, Timmy Fyrner, Nicholas A Sather, Mark T McClendon, Oscar A Carballo-Molina, Charles D James, Tadanori Tomita, Guifa Xi, Samuel I Stupp
{"title":"再生糖肽支架增强BMP-4活性治疗小儿胶质瘤。","authors":"Cara S Smith, Timmy Fyrner, Nicholas A Sather, Mark T McClendon, Oscar A Carballo-Molina, Charles D James, Tadanori Tomita, Guifa Xi, Samuel I Stupp","doi":"10.1007/s40883-025-00543-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>Pediatric high-grade gliomas (pHGGs) are among the most devastating cancers in children. These tumors have remained largely incurable, despite the many approaches that have been applied for their treatment. Here we use scaffolds of glycopeptide nanostructures designed for regenerative therapies to bind and present bone morphogenetic protein (BMP-4) in vivo to differentiate glioma cells and render them more susceptible to traditional chemotherapeutics. Interestingly, we discovered that the presentation of BMP-4 on these glycopeptide structures alone, without the use of a traditional chemotherapy, resulted in reduced tumor growth and enhanced survival in an orthotopic xenograft pediatric high-grade glioma tumor mouse model. Thus, this strategy has the potential to serve as a future chemotherapy-free platform for treating pHGGs which may have significantly reduced comorbidities.</p><p><strong>Lay summary: </strong>Pediatric glioblastoma (pGBM) is an aggressive brain cancer with poor survival rates despite surgery, radiation, and chemotherapy. The growth factor BMP-4 shows promise as a treatment, but its short half-life limits its potential as a future pGBM therapeutic. We developed nanostructures made from sugar-inspired molecules known as glycopeptide amphiphile molecules (gPA) that can bind, stabilize, and enhance the activity of BMP-4. When presented on gPA, BMP-4 directed pGBM cells to become less stem cell-like which slowed tumor growth in a mouse model. This approach highlights a potential strategy to improve BMP-4 delivery to advance therapeutic options for children with pGBM.</p><p><strong>Future work: </strong>Development of chemically scalable glycosylated supramolecular structures, such as the one described here, can be used to bind and present BMP-4 as well as other proteins for future drug delivery applications in the nervous system and beyond. Future research should also investigate how these therapies can be co-administered with chemotherapeutics.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40883-025-00543-5.</p>","PeriodicalId":20936,"journal":{"name":"Regenerative Engineering and Translational Medicine","volume":"11 4","pages":"1121-1131"},"PeriodicalIF":3.1000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12852313/pdf/","citationCount":"0","resultStr":"{\"title\":\"Regenerative Glycopeptide Scaffolds Enhance BMP-4 Activity To Treat Pediatric Glioma.\",\"authors\":\"Cara S Smith, Timmy Fyrner, Nicholas A Sather, Mark T McClendon, Oscar A Carballo-Molina, Charles D James, Tadanori Tomita, Guifa Xi, Samuel I Stupp\",\"doi\":\"10.1007/s40883-025-00543-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Abstract: </strong>Pediatric high-grade gliomas (pHGGs) are among the most devastating cancers in children. These tumors have remained largely incurable, despite the many approaches that have been applied for their treatment. Here we use scaffolds of glycopeptide nanostructures designed for regenerative therapies to bind and present bone morphogenetic protein (BMP-4) in vivo to differentiate glioma cells and render them more susceptible to traditional chemotherapeutics. Interestingly, we discovered that the presentation of BMP-4 on these glycopeptide structures alone, without the use of a traditional chemotherapy, resulted in reduced tumor growth and enhanced survival in an orthotopic xenograft pediatric high-grade glioma tumor mouse model. Thus, this strategy has the potential to serve as a future chemotherapy-free platform for treating pHGGs which may have significantly reduced comorbidities.</p><p><strong>Lay summary: </strong>Pediatric glioblastoma (pGBM) is an aggressive brain cancer with poor survival rates despite surgery, radiation, and chemotherapy. The growth factor BMP-4 shows promise as a treatment, but its short half-life limits its potential as a future pGBM therapeutic. We developed nanostructures made from sugar-inspired molecules known as glycopeptide amphiphile molecules (gPA) that can bind, stabilize, and enhance the activity of BMP-4. When presented on gPA, BMP-4 directed pGBM cells to become less stem cell-like which slowed tumor growth in a mouse model. This approach highlights a potential strategy to improve BMP-4 delivery to advance therapeutic options for children with pGBM.</p><p><strong>Future work: </strong>Development of chemically scalable glycosylated supramolecular structures, such as the one described here, can be used to bind and present BMP-4 as well as other proteins for future drug delivery applications in the nervous system and beyond. Future research should also investigate how these therapies can be co-administered with chemotherapeutics.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40883-025-00543-5.</p>\",\"PeriodicalId\":20936,\"journal\":{\"name\":\"Regenerative Engineering and Translational Medicine\",\"volume\":\"11 4\",\"pages\":\"1121-1131\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12852313/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Regenerative Engineering and Translational Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s40883-025-00543-5\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/12/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative Engineering and Translational Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s40883-025-00543-5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/12/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
Regenerative Glycopeptide Scaffolds Enhance BMP-4 Activity To Treat Pediatric Glioma.
Abstract: Pediatric high-grade gliomas (pHGGs) are among the most devastating cancers in children. These tumors have remained largely incurable, despite the many approaches that have been applied for their treatment. Here we use scaffolds of glycopeptide nanostructures designed for regenerative therapies to bind and present bone morphogenetic protein (BMP-4) in vivo to differentiate glioma cells and render them more susceptible to traditional chemotherapeutics. Interestingly, we discovered that the presentation of BMP-4 on these glycopeptide structures alone, without the use of a traditional chemotherapy, resulted in reduced tumor growth and enhanced survival in an orthotopic xenograft pediatric high-grade glioma tumor mouse model. Thus, this strategy has the potential to serve as a future chemotherapy-free platform for treating pHGGs which may have significantly reduced comorbidities.
Lay summary: Pediatric glioblastoma (pGBM) is an aggressive brain cancer with poor survival rates despite surgery, radiation, and chemotherapy. The growth factor BMP-4 shows promise as a treatment, but its short half-life limits its potential as a future pGBM therapeutic. We developed nanostructures made from sugar-inspired molecules known as glycopeptide amphiphile molecules (gPA) that can bind, stabilize, and enhance the activity of BMP-4. When presented on gPA, BMP-4 directed pGBM cells to become less stem cell-like which slowed tumor growth in a mouse model. This approach highlights a potential strategy to improve BMP-4 delivery to advance therapeutic options for children with pGBM.
Future work: Development of chemically scalable glycosylated supramolecular structures, such as the one described here, can be used to bind and present BMP-4 as well as other proteins for future drug delivery applications in the nervous system and beyond. Future research should also investigate how these therapies can be co-administered with chemotherapeutics.
Graphical abstract:
Supplementary information: The online version contains supplementary material available at 10.1007/s40883-025-00543-5.
期刊介绍：
Regenerative Engineering is an international journal covering convergence of the disciplines of tissue engineering, advanced materials science, stem cell research, the physical sciences, and areas of developmental biology. This convergence brings exciting opportunities to translate bench-top research into bedside methods, allowing the possibility of moving beyond maintaining or repairing tissues to regenerating them. The journal encourages both top-down engineering approaches and bottom-up strategies integrating materials science with stem cell research and developmental biology. Convergence papers on instructive biomaterials, stimuli-responsive biomaterials, micro- and nano-patterning for regenerative engineering, elastomeric biomaterials, hydrogels for tissue engineering, and rapid prototyping and bioprinting approaches are particularly welcome.
The journal provides a premier, single-blind peer-reviewed forum for the publication of original papers, authoritative reviews, rapid communications, news and views, and opinion papers addressing the most important issues and efforts toward successfully regenerating complex human tissues and organs. All research articles feature a lay abstract highlighting the relevance and future impact for patients, government and other health officials, and members of the general public. Bridging the gap between the lab and the clinic, the journal also serves as a dedicated platform for showcasing translational research that brings basic scientific research and discoveries into clinical methods and therapies, contributing to the improvement of human health care.
Topics covered in Regenerative Engineering and Translational Medicine include:
Advanced materials science for regenerative and biomedical applicationsStem cells for tissue regenerationDrug delivery for tissue regenerationNanomaterials and nanobiotechnology for tissue regenerationStudies combining tissue engineering/regeneration with developmental biologyConvergence research in pre-clinical and clinical phases
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
