Nanodrug Inducing Autophagy Inhibition and Mitochondria Dysfunction for Potentiating Tumor Photo-Immunotherapy.
Nanodrug Inducing Autophagy Inhibition and Mitochondria Dysfunction for Potentiating Tumor Photo-Immunotherapy.
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DOI：
10.1002/smll.202300280
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发表时间：
2023-04
期刊：
影响因子：
13.3
通讯作者：
Hong Xiao;Xiaoxia Li;Bo Li;Shuguang Yang;Jingya Qin;Shisong Han;Jie Ren;X. Shuai
中科院分区：
文献类型：
--
作者：
Hong Xiao;Xiaoxia Li;Bo Li;Shuguang Yang;Jingya Qin;Shisong Han;Jie Ren;X. Shuai
肿瘤免疫原性差和免疫抑制性肿瘤微环境（TME）阻碍了抗癌免疫治疗。在此，开发了一种脂质体纳米药物，共封装盐酸多西环素（Doxy）和二氢卟酚e6（Ce6），可同时诱导自噬抑制和线粒体功能障碍，从而增强肿瘤光免疫治疗。在近红外激光照射下，Ce6 产生细胞毒性活性氧 (ROS)，并引发强大的光动力疗法 (PDT) 诱导的免疫原性细胞死亡 (ICD)，以实现免疫抑制性 TME 重塑。此外，Doxy诱导线粒体功能障碍，增加ROS的产生并增强PDT，以发挥更有效的杀伤作用和更强大的ICD。同时，Doxy通过有效的自噬抑制增加肿瘤细胞表面MHC-I的表达，从而导致更有效的抗原呈递和CTL识别，从而增加肿瘤的免疫原性。这些纳米药物通过结合 Ce6 介导的 PDT 和 Doxy 诱导的自噬抑制和线粒体功能障碍，引发显着的抗肿瘤治疗。所开发的纳米药物代表了改善癌症免疫治疗的高效策略。
Anticancer immunotherapy is hampered by the poor tumor immunogenicity and immunosuppressive tumor microenvironment (TME). Herein, a liposome nanodrug co-encapsulating doxycycline hydrochloride (Doxy) and chlorin e6 (Ce6) to simultaneously induce autophagy inhibition and mitochondria dysfunction for potentiating tumor photo-immunotherapy is developed. Under near infrared laser irradiation, Ce6 generates cytotoxic reactive oxygen species (ROS) and elicits robust photodynamic therapy (PDT)-induced immunogenic cell death (ICD) for immunosuppressive TME remodeling. In addition, Doxy induced mitochondria dysfunction, which increases ROS generation and enhances PDT to exert more potent killing effect and more powerful ICD. Meanwhile, Doxy increases MHC-I expression on tumor cells surface by efficient autophagy inhibition, leading to more efficient antigen presentation and CTLs recognition to increase tumor immunogenicity. The nanodrugs elicit remarkable antitumor therapy by combining Ce6-mediated PDT and Doxy-induced autophagy inhibition and mitochondria dysfunction. The developed nanodrugs represent a highly efficient strategy for improving cancer immunotherapy.