In Situ Attached Photothermal Immunomodulation-Enhanced Nanozyme for the Inhibition of Postoperative Malignant Glioma Recurrence.
In Situ Attached Photothermal Immunomodulation-Enhanced Nanozyme for the Inhibition of Postoperative Malignant Glioma Recurrence.
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DOI：
10.1021/acsnano.3c03696
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发表时间：
2023-07
期刊：
影响因子：
17.1
通讯作者：
Dekang Nie;Yue-Juan Ling;Wenxin Lv;Qianqian Liu;Song Deng;J. Shi;Jun-ling Yang;Y. Yang;Siguang Ouyang;Yue Huang;Yi Wang;Rongqin Huang;Wei Shi
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文献类型：
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作者：
Dekang Nie;Yue-Juan Ling;Wenxin Lv;Qianqian Liu;Song Deng;J. Shi;Jun-ling Yang;Y. Yang;Siguang Ouyang;Yue Huang;Yi Wang;Rongqin Huang;Wei Shi
胶质母细胞瘤(GBM)是最具挑战性的恶性脑肿瘤之一。在此，我们描述了一种纳米酶止血基质策略，并在肿瘤腔内原位应用，同时作为光热剂，诱导GBM手术切除后的免疫原性细胞死亡，以增强抗肿瘤免疫并延缓肿瘤复发。止血基质系统(Surgiflo@PCN)包含Surgiflo，这是一种多空间结构，可用于穿透不同形状的肿瘤腔，以防止术后肿瘤腔出血。此外，在近红外(808 Nm)激光照射下，多孔钯-铜纳米簇(PCN)具有可调节的类酶活性(氧化酶、过氧化物酶和过氧化氢酶)，负责形成活性氧物种(ROS)。当Surgiflo@PCN进入切除的肿瘤腔后，首先通过ROS和光热疗法(PTT)直接杀伤胶质瘤细胞。第二个作用是PCN增强的氧化应激和PTT诱导免疫原性细胞死亡，从而逆转免疫抑制的肿瘤微环境，增强抗肿瘤免疫应答。这根除了残留的胶质瘤细胞，防止了复发。集体研究结果表明，Surgiflo@PCN通过ROS和PTT直接杀死胶质瘤细胞，增强抗胶质瘤免疫，间接杀死胶质瘤细胞。“一石二鸟”策略可能成为治疗GBM患者的有效光热免疫疗法。
Glioblastoma (GBM) is one of the most challenging malignant brain tumors to treat. Herein, we describe a nanoenzyme hemostatic matrix strategy with the tumor cavity in situ application that simultaneously serves as photothermal agent and induces immunogenic cell death after GBM surgical resection to enhance the antitumor immunity and delay tumor recurrence. The hemostatic matrix system (Surgiflo@PCN) contains Surgiflo, a multispace structure that can be used to penetrate different shapes of tumor cavities to prevent postoperative tumor cavity hemorrhage. As well, porous palladium-copper nanoclusters (PCNs) have adjustable enzyme-like activities (oxidase, peroxidase, and catalase) responsible for formation of reactive oxygen species (ROS) under near-infrared (808 nm) laser irradiation. When the Surgiflo@PCN entered the resected tumor cavity, the first action was the direct killing of glioma cells via ROS and photothermal therapy (PTT). The second action was the induction of immunogenic cell death by PCN-enhanced oxidative stress and PTT, which reversed the immunosuppressive tumor microenvironment and enhanced the antitumor immune response. This eradicated residual glioma cells and prevented recurrence. The collective findings demonstrate that Surgiflo@PCN kills glioma cells directly through ROS and PTT and enhances antiglioma immunity and kills glioma cells indirectly. The "one-stone, two-birds" strategy could become an effective photothermal immunotherapy in GBM patients.