癌症研究
先天免疫系统
黑色素瘤
干扰素基因刺激剂
刺
癌症免疫疗法
免疫疗法
免疫系统
免疫原性细胞死亡
活性氧
光动力疗法
化学
药理学
医学
生物
免疫学
细胞生物学
有机化学
工程类
航空航天工程
作者
Hui Tao,Jia Tan,Hanchen Zhang,Hong Ren,Zhongli Cai,Hanhan Liu,Baohong Wen,Jiaqi Du,Gaoyang Li,Shijie Chen,Haihua Xiao,Zhihong Deng
标识
DOI:10.1002/advs.202302895
摘要
The cGAS-STING pathway, as a vital innate immune signaling pathway, has attracted considerable attention in tumor immunotherapy research. However, STING agonists are generally incapable of targeting tumors, thus limiting their clinical applications. Here, a photodynamic polymer (P1) is designed to electrostatically couple with 56MESS-a cationic platinum (II) agent-to form NPPDT -56MESS. The accumulation of NPPDT -56MESS in the tumors increases the efficacy and decreases the systemic toxicity of the drugs. Moreover, NPPDT -56MESS generates reactive oxygen species (ROS) under the excitation with an 808 nm laser, which then results in the disintegration of NPPDT -56MESS. Indeed, the ROS and 56MESS act synergistically to damage DNA and mitochondria, leading to a surge of cytoplasmic double-stranded DNA (dsDNA). This way, the cGAS-STING pathway is activated to induce anti-tumor immune responses and ultimately enhance anti-cancer activity. Additionally, the administration of NPPDT -56MESS to mice induces an immune memory effect, thus improving the survival rate of mice. Collectively, these findings indicate that NPPDT -56MESS functions as a chemotherapeutic agent and cGAS-STING pathway agonist, representing a combination chemotherapy and immunotherapy strategy that provides novel modalities for the treatment of uveal melanoma.
科研通智能强力驱动
Strongly Powered by AbleSci AI