Lu Pei, Liu Xianjun, Chu Xia, Wang Fenglin, Jiang Jian-Hui
State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University Changsha 410082 P. R. China
Chem Sci. 2023 Feb 8;14(10):2562-2571. doi: 10.1039/d2sc07044h. eCollection 2023 Mar 8.
Pyroptotic immunogenic cell death presents an emerging targeting pathway for cancer immunotherapy. We report a novel membrane-tethered activation design of a photosensitizer (PS) that boosts systemic anti-tumor immunity to primary and distant tumors pyroptosis induction. The membrane-tethered PS is designed by installing a new phenylbenzopyrylium PS with zwitterionic lipid anchors and a target-cleavable caging moiety. This design affords excellent membrane tethering and enzymatic activation of the PS, exerting specific phototoxicity to cancer cells and inducing effective pyroptosis. Our design demonstrates prolonged circulation, long-lasting fluorogenic imaging and persistent photodynamic therapy of immunogenic 'cold' tumors , eliciting potent immunity toward local and abscopal tumors promoted maturation of dendritic cells and recruitment of cytotoxic T lymphocytes. This design affords a promising approach for enhancing systemic antitumor immunity for cancer immunotherapy.
焦亡性免疫原性细胞死亡为癌症免疫治疗提供了一种新兴的靶向途径。我们报告了一种新型的光敏剂（PS）膜 tethered 激活设计，该设计可增强对原发性和远处肿瘤的全身抗肿瘤免疫，诱导焦亡。膜 tethered PS 是通过安装带有两性离子脂质锚和可靶向切割的笼蔽部分的新型苯基苯并吡喃鎓 PS 来设计的。这种设计赋予了 PS 出色的膜 tethering 和酶促激活能力，对癌细胞发挥特异性光毒性并诱导有效的焦亡。我们的设计展示了免疫原性“冷”肿瘤的延长循环、持久的荧光成像和持续的光动力治疗，引发对局部和远隔肿瘤的强效免疫，促进树突状细胞成熟并募集细胞毒性 T 淋巴细胞。这种设计为增强癌症免疫治疗的全身抗肿瘤免疫提供了一种有前景的方法。
