Lysosome-Anchoring Activation Design of Type I Photosensitizer Evokes Pyroptosis and Antitumor Immunity,ACS Materials Letters

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Lysosome-Anchoring Activation Design of Type I Photosensitizer Evokes Pyroptosis and Antitumor Immunity
ACS Materials Letters ( IF 9.6 ) Pub Date : 2024-04-05 , DOI: 10.1021/acsmaterialslett.4c00135
Guo Li ₁ , Liuwei Gu ₁ , Chaojie Yang ₁ , Xiaojie Kong ₁ , Yuling Qin ₁ , Li Wu ₁

Affiliation

Pyroptosis, an inflammatory form of programmed cell death, has attracted growing attention as a promising pathway for cancer immunotherapy. However, few molecular design strategies with near-infrared (NIR) photoactivated pyroptosis inducers have been developed. Herein, a lysosome-targeted NIR type I photoinduced superoxide radical (O₂^–•) generator (ENBS) that can evoke pyroptosis and antitumor immunity was presented here for the first time. In this work, ENBS not only selectively accumulates in lysosomes and disrupts the integrity of lysosomes but also induces gasdermin D (GSDMD) mediated pyroptosis. As a result, it finally promotes the maturation of dendritic cells (DCs), achieving T-cell-mediated immune activation in vivo. To the best of our knowledge, this is the first example of an NIR photoactivated superoxide radical pyroptosis generator-based immunotherapy system through the caspase-1/GSDMD pathway, anticipated to provide valuable guidelines for pyroptosis-mediated cancer immunotherapy.

中文翻译：

I 型光敏剂的溶酶体锚定激活设计可引起细胞焦亡和抗肿瘤免疫

细胞焦亡是一种程序性细胞死亡的炎症形式，作为癌症免疫治疗的一种有前景的途径而受到越来越多的关注。然而，目前已经开发出很少的近红外（NIR）光激活焦亡诱导剂的分子设计策略。在此，首次提出了一种可引起细胞焦亡和抗肿瘤免疫的溶酶体靶向近红外I型光诱导超氧自由基（O ₂^–• ）发生器（ENBS）。在这项工作中，ENBS不仅选择性地在溶酶体中积累并破坏溶酶体的完整性，而且还诱导gasdermin D (GSDMD)介导的细胞焦亡。最终促进树突状细胞（DC）的成熟，实现体内T细胞介导的免疫激活。据我们所知，这是通过 caspase-1/GSDMD 途径基于近红外光激活超氧化物自由基焦亡发生器的免疫治疗系统的第一个例子，预计将为焦亡介导的癌症免疫治疗提供有价值的指导。

更新日期：2024-04-05

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