中山大学化学学院毛宗万研究团队发现，碳酸酐酶IX(CAIX)锚定的铼(I)光敏剂可促进焦亡来增强肿瘤免疫。相关论文于2021年11月29日在线发表在《德国应用化学》杂志上。

研究人员设计了一种碳酸酐酶IX（CAIX）锚定的铼（I）光敏剂，命名为CA-Re，不仅可以在缺氧（纳摩尔级光毒性）下高效地进行I型和II型光动力治疗（PDT），还可以唤起gasdermin D（GSDMD）介导的细胞焦亡，从而有效刺激肿瘤免疫原性。同时，CA-Re可以同时破坏并自我报告膜完整性的丧失。因此，这促进了树突状细胞（DC）的成熟和抗原呈递能力，并充分激活了T细胞在体内的依赖性适应性免疫反应，最终在消灭原发肿瘤的同时也消灭了远处的肿瘤。

CA-Re是第一个基于金属复合物的焦亡诱导剂，这项工作为癌症金属免疫治疗提供了一个新颖的角度。

据悉，理想的癌症治疗不仅要消灭原发肿瘤，还要改善肿瘤微环境的免疫原性，从而达到满意的抗肿瘤免疫效果。

附：英文原文

Title: A Carbonic Anhydrase IX (CAIX)-Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti-Tumor Immunity

Author: Xuxian Su, Wen-Jin Wang, Qian Cao, Hang Zhang, Bin Liu, Yuyi Ling, Xiaotong Zhou, Zong-Wan Mao

Issue&Volume: 2021-11-29

Abstract: An ideal cancer treatment should not only destroy primary tumors, but also improve the immunogenicity of tumor microenvironment to achieve satisfactory anti-tumor immune effect.  Herein, we designed a carbonic anhydrase IX (CAIX)-anchored rhenium(I) photosensitizer, named as  CA-Re, not only performing type-I and type-II photodynamic therapy (PDT) with high efficiency under hypoxia (nanomolar-level phototoxicity), but also evoking gasdermin D (GSDMD) mediated pyroptotic cell death to effectively stimulate tumor immunogenicity. Meanwhile,  CA-Re could disrupt and self-report the loss of membrane integrity simultaneously. As a result, this promoted the maturation and antigen-presenting ability of dendritic cells (DCs), and fully activated T cells dependent adaptive immune response in vivo, eventually eliminating distant tumors at the same time as destroying primary tumors. To the best of our knowledge,  CA-Re  is the first metal complex-based pyroptosis inducer, and this work provides a tantalizing angle for cancer metalloimmunotherapy.

DOI: 10.1002/anie.202115800

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202115800