Cui Hao, Zhao Yu-Yue, Wu Qiong, You Yan, Lan Zhou, Zou Ke-Long, Cheng Guo-Wang, Chen Hao, Han Yan-Hua, Chen Yan, Qi Xiang-Dong, Meng Xian-Wei, Ma Li-Min, Yu Guang-Tao
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, China.
Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Bioact Mater. 2023 Dec 8;33:532-544. doi: 10.1016/j.bioactmat.2023.11.010. eCollection 2024 Mar.
The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.
由于低响应率和全身性免疫相关不良事件,癌症免疫疗法的临床应用并不理想。微波热疗可作为一种协同免疫疗法来增强抗肿瘤效果。在此,我们设计了一种基于钆的金属有机框架(Gd-MOF)纳米系统用于磁共振成像(MRI)引导的热疗和协同免疫疗法,该系统在药物负载和肿瘤组织渗透方面具有高性能。程序性死亡受体1(PD-1)抑制剂(aPD-1)最初被负载于多孔Gd-MOF(Gd/M)纳米系统中。然后,相变材料(PCM)和癌细胞膜在Gd/MP表面进一步依次修饰,以获得Gd-MOF@aPD-1@CM(Gd/MPC)。当进入肿瘤微环境(TME)时,Gd/MPC通过微波热响应诱导肿瘤细胞发生免疫原性死亡,改善肿瘤抑制性免疫微环境,并通过释放aPD-1进一步增强T细胞的抗肿瘤能力。同时,Gd/MPC可用于增强磁共振成像。转录组学数据显示,癌细胞中丝裂原和应激激活蛋白激酶2(MSK2)的下调导致原癌基因c-fos和原癌基因c-jun的下调,并最终导致治疗后癌细胞凋亡。总体而言,Gd/MPC纳米系统不仅解决了系统副作用问题,还通过PCM实现了药物的控释,为癌症联合免疫疗法的发展提供了一个有前景的诊疗纳米平台。
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