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A Mitochondria-Targeted NIR-II AIEgen Induced Pyroptosis for Enhanced Tumor Immunotherapy
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-06-07 , DOI: 10.1002/adhm.202301693 Kaiwu Yu 1 , Binglin Ye 2 , Huang Yang 3 , Xinxin Xu 1 , Zhengwei Mao 2, 3 , Qinghua Zhang 1 , Mei Tian 4 , Haoke Zhang 3 , Hong Zhang 4 , Qinggang He 1
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-06-07 , DOI: 10.1002/adhm.202301693 Kaiwu Yu 1 , Binglin Ye 2 , Huang Yang 3 , Xinxin Xu 1 , Zhengwei Mao 2, 3 , Qinghua Zhang 1 , Mei Tian 4 , Haoke Zhang 3 , Hong Zhang 4 , Qinggang He 1
Affiliation
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Cancer immunotherapy is a favorable strategy for facilitating anti-tumor immunity, but it shows limited benefits in clinical practice owing to the immunosuppressive tumor microenvironment. Pyroptosis shows great immunostimulatory effect on tumor, whereas the lack of pyroptotic inducer with imaging property has restricted its progress in tumor theranostics. Herein, a mitochondria-targeted aggregation-induced emission (AIE) luminogen (TPA-2TIN) with NIR-II emission is designed for highly efficient induction of tumor cell pyroptosis. The fabricated TPA-2TIN nanoparticles can be efficiently taken up by tumor cells and selectively accumulated in tumor for a long term observed by NIR-II fluorescence imaging. More importantly, the TPA-2TIN nanoparticles can effectively stimulate immune responses both in vitro and in vivo mediated by the mitochondrial dysfunctions and the subsequent activation of the pyroptotic pathway. Ultimately, the reversal of the immunosuppressive tumor microenvironment significantly enhances the immune checkpoint therapy. This study paves a new avenue for adjuvant immunotherapy of cancer.
中文翻译：
用于增强肿瘤免疫治疗的线粒体靶向 NIR-II AIEgen 诱导细胞焦亡
癌症免疫治疗是促进抗肿瘤免疫的有利策略，但由于免疫抑制的肿瘤微环境，其在临床实践中显示出的益处有限。焦亡对肿瘤具有巨大的免疫刺激作用，但缺乏具有成像特性的焦亡诱导剂限制了其在肿瘤治疗诊断方面的进展。在此，设计了一种具有 NIR-II 发射功能的线粒体靶向聚集诱导发射 (AIE) 发光剂 (TPA-2TIN)，用于高效诱导肿瘤细胞焦亡。制备的 TPA-2TIN 纳米粒子可以被肿瘤细胞有效摄取，并选择性地积累在肿瘤中，并可通过 NIR-II 荧光成像长期观察到。更重要的是，TPA-2TIN纳米颗粒可以有效地刺激由线粒体功能障碍和随后的焦亡途径激活介导的体外和体内免疫反应。最终，免疫抑制肿瘤微环境的逆转显着增强了免疫检查点治疗。这项研究为癌症辅助免疫治疗开辟了一条新途径。
更新日期：2023-06-07
中文翻译：
用于增强肿瘤免疫治疗的线粒体靶向 NIR-II AIEgen 诱导细胞焦亡
癌症免疫治疗是促进抗肿瘤免疫的有利策略，但由于免疫抑制的肿瘤微环境，其在临床实践中显示出的益处有限。焦亡对肿瘤具有巨大的免疫刺激作用，但缺乏具有成像特性的焦亡诱导剂限制了其在肿瘤治疗诊断方面的进展。在此，设计了一种具有 NIR-II 发射功能的线粒体靶向聚集诱导发射 (AIE) 发光剂 (TPA-2TIN)，用于高效诱导肿瘤细胞焦亡。制备的 TPA-2TIN 纳米粒子可以被肿瘤细胞有效摄取，并选择性地积累在肿瘤中，并可通过 NIR-II 荧光成像长期观察到。更重要的是，TPA-2TIN纳米颗粒可以有效地刺激由线粒体功能障碍和随后的焦亡途径激活介导的体外和体内免疫反应。最终，免疫抑制肿瘤微环境的逆转显着增强了免疫检查点治疗。这项研究为癌症辅助免疫治疗开辟了一条新途径。
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