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【IF 14.7】超声触发和糖基化抑制增强的肿瘤压力催化免疫疗法

分类:引用文献   发布时间 2024/10/23   阅读: 547
杂志名称:Nature Communications
影响因子:14.7
文章题目:Ultrasound-triggered and glycosylation inhibition-enhanced tumor piezocatalytic immunotherapy
DOI: https://doi.org/10.1038/s41467-024-53392-1
第一作者:Yinying Pu,Bangguo Zhou,Jinhong Bing,Liang Wang,Mingqi Chen,Yucui Shen,Shuang Gao,Min Zhou,Wencheng Wu,Jianlin Shi
作者单位:
中国科学院上海陶瓷研究所
中国电子科技大学四川省人民医院四川省医学科学院
浙江大学医学院附属第一医院
同济大学上海第四人民医院

引用YOBIBIO产品:
Phosphate buffer solution (PBS)
Dulbecco’s modified eagle medium (DMEM)
calcein, 4, 6-diamidino-2-phenylindole (DAPI)
propidium iodide (PI)
fluorescein isothiocyanate (FITC)
Superior FBS (U11-020A)
cell counting Kit-8 (CCK-8)

文章摘要:
Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system to attack tumor cells. However, a high level of N-glycosylation can protect tumor cells, compromising the anticancer immunity of nanocatalytic immunotherapy. Here, we show a 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold for enhanced cancer piezocatalytic immunotherapy. After the implantation in the tumor, DBG generates both reactive oxygen species (ROS) and piezoelectric signals when excited with ultrasound irradiation, significantly promoting the activation of anticancer immunity. Meanwhile, 2-DG released from ROS-sensitive DBG disrupts the N-glycans synthesis, further overcoming the immunosuppressive microenvironment of tumors. The synergy effects of ultrasound-triggered and glycosylation inhibition enhanced tumor piezocatalytic immunotherapy are demonstrated on four mouse cancer models. A “hot” tumor-immunity niche is produced to inhibit tumor progress and lung metastasis and elicit strong immune memory effects. This work provides a promising piezocatalytic immunotherapy for malignant solid tumors featuring both low immunogenicity and high levels of N-glycosylation.

纳米催化免疫疗法因其快速激活免疫系统以攻击肿瘤细胞而具有极好的未来癌症治疗潜力。然而,高水平的 N-糖基化可以保护肿瘤细胞,损害纳米催化免疫疗法的抗癌免疫力。在这里,我们展示了一种用于增强癌症压迫免疫治疗的 2-脱氧葡萄糖 (2-DG) 和铁氧体铋共负载凝胶 (DBG) 支架。植入肿瘤后,DBG 在超声照射下激发时产生活性氧 (ROS) 和压电信号,显着促进抗癌免疫的激活。同时,ROS 敏感的 DBG 释放的 2-DG 破坏了 N-糖的合成,进一步克服了肿瘤的免疫抑制微环境。超声触发和糖基化抑制增强的肿瘤压电催化免疫疗法的协同作用已在四种小鼠癌症模型上得到证明。产生“热”肿瘤免疫生态位以抑制肿瘤进展和肺转移,并引发强烈的免疫记忆效应。这项工作为具有低免疫原性和高水平 N-糖基化的恶性实体瘤提供了一种有前途的压电催化免疫疗法。