肿瘤细胞治疗研究
英文原题：An Engineered Nanoplatform with Tropism Toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy.
An Engineered Nanoplatform with Tropism Toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy.
本研究提出了一种有前景的、用于靶向药物递送的辐射诱导趋向性策略，并展示了一个可增强放射免疫治疗疗效与安全性的强效纳米平台。
放疗联合免疫检查点阻断疗法为治疗多形性胶质母细胞瘤（GBM）提供了有前景的方法，但疗效有限及免疫相关不良事件（irAE）等问题仍然存在，主要原因是免疫调节剂无法直接靶向肿瘤微环境。为解决这一问题，研究开发了一种仿生纳米平台，将基因修饰的间充质干细胞（MSC）膜与生物活性纳米颗粒核心结合，用于趋化因子定向的 GBM 放射免疫治疗。过表达 CC 趋化因子受体 2（CCR2）的 MSC 膜充当“战术触角”，使纳米平台产生放射诱导的趋向性，靶向受照射胶质瘤中丰富的 CC 基序趋化因子配体 2（CCL2）。纳米颗粒核心由二硒键桥联的介孔二氧化硅纳米颗粒（MSN）和 PD-L1 抗体组成，可响应 X 射线释放药物并增强放射敏感性。在两种原位 GBM 小鼠模型中，该纳米平台增强免疫原性细胞死亡，提高 GBM 放射免疫治疗的疗效和特异性，同时减少 irAE。研究提出一种有前景的放射诱导趋向性靶向递送策略，并展示可增强放射免疫疗法疗效和安全性的纳米平台。
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 ( PD-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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