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用于增强乳腺癌光热免疫治疗的 GSH 耗竭脂质体佐剂。

GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer.

机构信息

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China.

出版信息

Sci Adv. 2020 Sep 2;6(36). doi: 10.1126/sciadv.abc4373. Print 2020 Sep.

Abstract

The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. In tumor cells, the ROS boosted the ABTS· production to activate photothermal-induced ICD. In DCs, it relieved the immunosuppression, promoting DC maturation (57%) and antigen presenting. As a result of the ML assistant, the therapeutic systems improved the infiltration of CD8 T cells to 53% in tumor tissues, eliciting strong abscopal effect and antimetastasis effect. The MLs were believed to be a superior candidate of adjuvants for enhancing immune response and cancer therapeutic efficacy.

摘要

肿瘤微环境的高氧化还原水平抑制了氧化处理和免疫反应。在这里,我们创新性地开发了马来酰亚胺脂质体 (ML) 佐剂,通过谷胱甘肽 (GSH) 的耗竭来促进免疫原性细胞死亡 (ICD) 的诱导和树突状细胞 (DCs) 的成熟,从而增强乳腺癌的光热免疫治疗。ML 可有效耗尽细胞内 GSH,并上调肿瘤细胞和 DCs 中的活性氧 (ROS)。在肿瘤细胞中,ROS 促进 ABTS·的产生,从而激活光热诱导的 ICD。在 DCs 中,它缓解了免疫抑制,促进了 DC 的成熟 (57%) 和抗原呈递。由于 ML 的辅助作用,治疗系统将肿瘤组织中 CD8 T 细胞的浸润提高到 53%,引发强烈的远隔效应和抗转移效应。ML 被认为是增强免疫反应和癌症治疗效果的优秀佐剂候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2119/7467696/44f4deb9bace/abc4373-F1.jpg

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