State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, PR China.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, PR China; State Key Laboratory of Fine Chemicals, Shenzhen Research Institute, Dalian University of Technology, Nanshan District, Shenzhen, 518057, PR China.
Biomaterials. 2021 Nov;278:121167. doi: 10.1016/j.biomaterials.2021.121167. Epub 2021 Sep 30.
Immune checkpoint blockade (ICB) therapy currently considered as to be effective way to cure cancer in clinic. However, the insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment always result in diminished efficacy of immunotherapy. Herein, we report the synthesis of an organic photo-immune activator NBS-1MT, the combination of photosensitizer and Indoleamine 2,3-dioxygenase (IDO) inhibitor effectively stimulates lysosomes oxidative stress the releases inflammatory cytokines. This process triggers pyroptosis for the considerable immunogenic cell death (ICD) while reversing suppressive tumor microenvironment. The photo-immune drug shows outstanding potential to activate caspase-1and then remove gasdermin-D (GSDMD), which could stimulate pyroptosis and also inhibit the tumor growth successfully in both primary and distant tumor. Furthermore, pyroptosis activated by photodynamic therapy (PDT) promotes the immune related factors release, and enhance the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) with the induction of ICD of tumor cells and the cascaded synergize with IDO inhibitor, so the general antitumor immune response could be strengthened effectively. Our research confirms that the use of NBS-1MT is a promising strategy to boost the immune response and eventually to inhibit tumor growth.
免疫检查点阻断（ICB）疗法目前被认为是临床治疗癌症的有效方法。然而，肿瘤的免疫原性不足和免疫抑制性肿瘤微环境总是导致免疫治疗效果减弱。在此，我们报告了一种有机光免疫激活剂 NBS-1MT 的合成，该激活剂将光敏剂和吲哚胺 2,3-双加氧酶（IDO）抑制剂结合在一起，有效地刺激溶酶体氧化应激并释放炎症细胞因子。这一过程引发细胞焦亡，导致大量免疫原性细胞死亡（ICD），同时逆转抑制性肿瘤微环境。该光免疫药物在原发性和远处肿瘤中均能成功激活 caspase-1 并去除天冬氨酸特异性半胱氨酸蛋白酶-1（GSDMD），从而刺激细胞焦亡，并抑制肿瘤生长。此外，光动力疗法（PDT）激活的细胞焦亡促进免疫相关因子的释放，并增强细胞毒性 T 淋巴细胞（CTLs）在肿瘤内的浸润，诱导肿瘤细胞 ICD，并与 IDO 抑制剂级联协同作用，从而有效增强抗肿瘤免疫反应。我们的研究证实，使用 NBS-1MT 是一种有前途的策略，可以增强免疫反应，最终抑制肿瘤生长。
