克服小儿中枢神经系统肿瘤的血脑屏障(BBB):免疫治疗和纳米药物驱动的策略。

IF 3.5 4区 医学 Q2 ONCOLOGY
Ali M Alaseem, Jihad Awadallah Alrehaili
{"title":"克服小儿中枢神经系统肿瘤的血脑屏障(BBB):免疫治疗和纳米药物驱动的策略。","authors":"Ali M Alaseem, Jihad Awadallah Alrehaili","doi":"10.1007/s12032-025-02984-y","DOIUrl":null,"url":null,"abstract":"<p><p>Pediatric central nervous system (CNS) tumors rank second among the fatal childhood malignancies, primarily due to the significant challenge posed by the blood-brain barrier (BBB), which limits the therapeutic delivery and contributes to poor clinical outcomes. This challenge is exacerbated by the distinct developmental traits of pediatric BBB, the immunosuppressive tumor microenvironment (TME), and the inherent diversity of different tumor types such as medulloblastoma and diffuse intrinsic pontine glioma (DIPG). Recent advances at the crossroad of immunotherapy and nanomedicine are paving the way for transformative strategies to penetrate the BBB and modify the immunogenic landscape within pediatric CNS tumors. Various nanoparticle-based approaches such as liposomes and polymeric nanoparticles to exosomes have been engineered with surface ligands like transferrin and lactoferrin to improve the BBB targeting in pediatric CNS tumors. Moreover, stimuli-responsive nanocarriers, such as pH- and enzyme-sensitive paradigms, are being implemented to enhance controlled drug release in the acidic and protease-rich TME. Additional, synergistic therapies that combine chemotherapeutics, immune checkpoint inhibitors, oncolytic viruses, and cancer vaccines are being adapted for pediatric patients, with enhanced drug delivery aided by nanocarrier formulations have led to significant tumor regression and prolonged survival in animal models. Additionally, tailored treatments utilizing genetic and pharmacokinetic biomarkers, along with innovative BBB-on-chip platforms, enable precise targeting and real-time monitoring of drug permeability across the barrier. In this review, we have emphasized that how a deeper understanding of pediatric BBB biology, targeted modulation of the barrier, and innovative nanotechnology-immunotherapy combinations is providing newer treatment modalities and less toxic therapies for children with CNS tumors.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"42 10","pages":"431"},"PeriodicalIF":3.5000,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Overcoming the blood-brain barrier (BBB) in pediatric CNS tumors: immunotherapy and nanomedicine-driven strategies.\",\"authors\":\"Ali M Alaseem, Jihad Awadallah Alrehaili\",\"doi\":\"10.1007/s12032-025-02984-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Pediatric central nervous system (CNS) tumors rank second among the fatal childhood malignancies, primarily due to the significant challenge posed by the blood-brain barrier (BBB), which limits the therapeutic delivery and contributes to poor clinical outcomes. This challenge is exacerbated by the distinct developmental traits of pediatric BBB, the immunosuppressive tumor microenvironment (TME), and the inherent diversity of different tumor types such as medulloblastoma and diffuse intrinsic pontine glioma (DIPG). Recent advances at the crossroad of immunotherapy and nanomedicine are paving the way for transformative strategies to penetrate the BBB and modify the immunogenic landscape within pediatric CNS tumors. Various nanoparticle-based approaches such as liposomes and polymeric nanoparticles to exosomes have been engineered with surface ligands like transferrin and lactoferrin to improve the BBB targeting in pediatric CNS tumors. Moreover, stimuli-responsive nanocarriers, such as pH- and enzyme-sensitive paradigms, are being implemented to enhance controlled drug release in the acidic and protease-rich TME. Additional, synergistic therapies that combine chemotherapeutics, immune checkpoint inhibitors, oncolytic viruses, and cancer vaccines are being adapted for pediatric patients, with enhanced drug delivery aided by nanocarrier formulations have led to significant tumor regression and prolonged survival in animal models. Additionally, tailored treatments utilizing genetic and pharmacokinetic biomarkers, along with innovative BBB-on-chip platforms, enable precise targeting and real-time monitoring of drug permeability across the barrier. In this review, we have emphasized that how a deeper understanding of pediatric BBB biology, targeted modulation of the barrier, and innovative nanotechnology-immunotherapy combinations is providing newer treatment modalities and less toxic therapies for children with CNS tumors.</p>\",\"PeriodicalId\":18433,\"journal\":{\"name\":\"Medical Oncology\",\"volume\":\"42 10\",\"pages\":\"431\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-08-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12032-025-02984-y\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12032-025-02984-y","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

小儿中枢神经系统(CNS)肿瘤在致死性儿童恶性肿瘤中排名第二,主要是由于血脑屏障(BBB)带来的重大挑战,这限制了治疗的传递并导致临床结果不佳。儿童血脑屏障的不同发育特征、免疫抑制肿瘤微环境(TME)以及不同肿瘤类型(如髓母细胞瘤和弥漫性固有脑桥胶质瘤(DIPG))的固有多样性加剧了这一挑战。在免疫治疗和纳米医学交叉路口的最新进展正在为穿透血脑屏障和改变儿童中枢神经系统肿瘤的免疫原性景观的变革性策略铺平道路。各种基于纳米颗粒的方法,如脂质体和聚合物纳米颗粒外泌体,已经与表面配体如转铁蛋白和乳铁蛋白一起设计,以改善儿童中枢神经系统肿瘤的血脑屏障靶向。此外,刺激反应型纳米载体,如pH敏感型和酶敏感型,正被用于增强酸性和富含蛋白酶的TME中的受控药物释放。​此外,利用遗传和药代动力学生物标志物的定制治疗,以及创新的bbb芯片平台,可以精确靶向和实时监测药物穿过屏障的渗透性。在这篇综述中,我们强调了如何更深入地了解儿童血脑屏障生物学,靶向调节屏障,以及创新的纳米技术-免疫治疗组合为儿童中枢神经系统肿瘤提供新的治疗方式和更低毒性的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Overcoming the blood-brain barrier (BBB) in pediatric CNS tumors: immunotherapy and nanomedicine-driven strategies.

Pediatric central nervous system (CNS) tumors rank second among the fatal childhood malignancies, primarily due to the significant challenge posed by the blood-brain barrier (BBB), which limits the therapeutic delivery and contributes to poor clinical outcomes. This challenge is exacerbated by the distinct developmental traits of pediatric BBB, the immunosuppressive tumor microenvironment (TME), and the inherent diversity of different tumor types such as medulloblastoma and diffuse intrinsic pontine glioma (DIPG). Recent advances at the crossroad of immunotherapy and nanomedicine are paving the way for transformative strategies to penetrate the BBB and modify the immunogenic landscape within pediatric CNS tumors. Various nanoparticle-based approaches such as liposomes and polymeric nanoparticles to exosomes have been engineered with surface ligands like transferrin and lactoferrin to improve the BBB targeting in pediatric CNS tumors. Moreover, stimuli-responsive nanocarriers, such as pH- and enzyme-sensitive paradigms, are being implemented to enhance controlled drug release in the acidic and protease-rich TME. Additional, synergistic therapies that combine chemotherapeutics, immune checkpoint inhibitors, oncolytic viruses, and cancer vaccines are being adapted for pediatric patients, with enhanced drug delivery aided by nanocarrier formulations have led to significant tumor regression and prolonged survival in animal models. Additionally, tailored treatments utilizing genetic and pharmacokinetic biomarkers, along with innovative BBB-on-chip platforms, enable precise targeting and real-time monitoring of drug permeability across the barrier. In this review, we have emphasized that how a deeper understanding of pediatric BBB biology, targeted modulation of the barrier, and innovative nanotechnology-immunotherapy combinations is providing newer treatment modalities and less toxic therapies for children with CNS tumors.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信