放射免疫疗法
胶质母细胞瘤
材料科学
癌症研究
向性
纳米技术
辐照
医学
病毒学
免疫学
单克隆抗体
病毒
物理
核物理学
抗体
作者
Zheng Wang,Fangman Chen,Yi Cao,Fan Zhang,Lina Sun,Chao Yang,Xiaochun Xie,Ziping Wu,Madi Sun,Fanshu Ma,Dan Shao,Kam W. Leong,Renjun Pei
标识
DOI:10.1002/adma.202314197
摘要
Abstract Combining radiotherapy with immune checkpoint blockade therapy offers a promising approach to treat glioblastoma multiforme (GBM), yet challenges such as limited effectiveness and immune‐related adverse events (irAEs) persist. These issues are largely due to the failure in targeting immunomodulators directly to the tumor microenvironment. To address this, a biomimetic nanoplatform that combines a genetically modified mesenchymal stem cell (MSC) membrane with a bioactive nanoparticle core for chemokine‐directed radioimmunotherapy of GBM is developed. The CC chemokine receptor 2 (CCR2)‐overexpressing MSC membrane acts as a tactical tentacle to achieve radiation‐induced tropism toward the abundant chemokine (CC motif) ligand 2 (CCL2) in irradiated gliomas. The nanoparticle core, comprising diselenide‐bridged mesoporous silica nanoparticles (MSNs) and PD‐L1 antibodies (αPD‐L1), enables X‐ray‐responsive drug release and radiosensitization. In two murine models with orthotopic GBM tumors, this nanoplatform reinvigorated immunogenic cell death, and augmented the efficacy and specificity of GBM radioimmunotherapy, with reduced occurrence of irAEs. This study suggests a promising radiation‐induced tropism strategy for targeted drug delivery, and presents a potent nanoplatform that enhances the efficacy and safety of radio‐immunotherapy.
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