肿瘤细胞治疗研究
英文原题：Engineered Macrophage-Membrane-Coated Nanoparticles with Enhanced PD-1 Expression Induce Immunomodulation for a Synergistic and Targeted Antiglioblastoma Activity.
胶质母细胞瘤（GBM）是恶性胶质瘤中最常见的亚型，以侵袭性浸润、高度恶性和预后不良为特征。
胶质母细胞瘤（GBM）是恶性胶质瘤中最常见的亚型，其特征为侵袭性浸润、高度恶性和预后不良。传统疗法抗GBM效果令人沮丧，原因除了血脑屏障（BBB）这一巨大障碍外，还在于免疫抑制微环境。联合免疫检查点阻断（ICB）已成为GBM治疗的重要组成部分。在此，我们报道一种工程化巨噬细胞膜包被的纳米平台，其程序性细胞死亡-1（PD-1）表达增强（PD-1-MM@PLGA/RAPA）。利用体外和体内GBM模型，我们证明PD-1-MM@PLGA/RAPA能够响应肿瘤微环境（TME）的招募，高效穿越BBB，纳米颗粒在肿瘤部位聚集。此外，我们还显示，由于CD8+细胞毒性T淋巴细胞（CTL）浸润增强，免疫应答得到提升。总之，我们提供了一种新的纳米平台，用于增强ICB联合传统化疗治疗GBM及许多其他癌症。
Glioblastoma (GBM), the most common subtype of malignant gliomas, is characterized by aggressive infiltration, high malignancy, and poor prognosis. The frustrating anti-GBM outcome of conventional therapeutics is due to the immunosuppressive milieu, in addition to the formidable obstacle of the blood-brain barrier (BBB). Combination therapy with an immune checkpoint blockade (ICB) has emerged as a critical component in the treatment of GBM. Here, we report an engineered macrophage-membrane-coated nanoplatform with enhanced programmed cell death-1 (PD-1) expression (PD-1-MM@PLGA/RAPA). Using both in vitro and in vivo GBM models, we demonstrate that PD-1-MM@PLGA/RAPA can efficiently traverse across the BBB in response to the tumor microenvironment (TME) recruitment with nanoparticles accumulating at the tumor site. Furthermore, we show a boosted immune response as a result of enhancing CD8 + cytotoxic T-lymphocyte (CTL) infiltration. Together we provide a new nanoplatform for enhancing ICB in combination with conventional chemotherapy for GBM and many other cancers.
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