School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510006, P. R. China.
Angew Chem Int Ed Engl. 2022 Mar 1;61(10):e202116669. doi: 10.1002/anie.202116669. Epub 2022 Jan 20.
Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano-regulator (SPN ) with cascading activation for combinational photodynamic cancer immunotherapy. SPN comprises an immunoregulator (M-Trp: 1-methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker-cleavable linker. Under near-infrared photoirradiation, SPN produces singlet oxygen to induce immunogenic apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M-Trp for indoleamine 2,3-dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPN -mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis.
联合光免疫疗法有望抑制肿瘤；然而，仅在肿瘤中激活其免疫药物作用的智能光疗剂却很少被开发出来。在此，我们报道了一种具有级联激活作用的用于联合光动力癌症免疫治疗的半导体聚合物（SP）纳米调节剂（SPN）。SPN 由一个免疫调节剂（M-Trp：1-甲基色氨酸）通过凋亡生物标志物可切割的连接子连接到 SP 主链的侧链上。在近红外光照射下，SPN 产生单线态氧诱导免疫原性细胞凋亡。同时，上调一种凋亡生物标志物，触发 M-Trp 的特异性切割以抑制吲哚胺 2,3-双加氧酶（IDO）活性、减少调节性 T 细胞和浸润细胞毒性 T 淋巴细胞。SPN 介导的联合光动力免疫疗法因此重新编程肿瘤免疫微环境，有效抑制肿瘤，并抑制肺转移。
