Tian Hao, Li Wenxi, Wang Guohao, Tian Ye, Yan Jie, Yu Xinying, Yan Ziliang, Feng Yuzhao, Dai Yunlu
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
MoE Frontiers Science Center for Precision Oncology, University of Macau, Macau SAR, 999078, China.
Angew Chem Int Ed Engl. 2024 Dec 9;63(50):e202411498. doi: 10.1002/anie.202411498. Epub 2024 Oct 16.
New generation of nanomaterials with organelle-level precision provide significant promise for targeted attacks on mitochondria, exhibiting remarkable therapeutic potency. Here, we report a novel amphiphilic phenolic polymer (PF) for the mitochondria-targeted photodynamic therapy (PDT), which can trigger excessive mitochondrial DNA (mtDNA) damage by the synergistic action of oxidative stress and furan-mediated DNA cross-linking. Moreover, the phenolic units on PF enable further self-assembly with Mn via metal-phenolic coordination to form metal-phenolic nanomaterial (PFM). We focus on the synergistic activation of the cGAS-STING pathway by Mn and tumor-derived mtDNA in tumor-associated macrophages (TAMs), and subsequently repolarizing M2-like TAMs to M1 phenotype. We highlight that PFM facilitates the cGAS-STING-dependent immunity at the organelle level for potent antitumor efficacy.
具有细胞器水平精度的新一代纳米材料为靶向攻击线粒体带来了巨大希望，展现出显著的治疗潜力。在此，我们报告了一种用于线粒体靶向光动力疗法（PDT）的新型两亲性酚醛聚合物（PF），它可通过氧化应激和呋喃介导的DNA交联的协同作用引发过量线粒体DNA（mtDNA）损伤。此外，PF上的酚单元能够通过金属-酚配位与锰进一步自组装形成金属-酚纳米材料（PFM）。我们着重研究了锰与肿瘤相关巨噬细胞（TAM）中肿瘤来源的mtDNA对cGAS-STING通路的协同激活作用，随后将M2型TAM重极化至M1表型。我们强调，PFM在细胞器水平促进了依赖cGAS-STING的免疫反应，从而实现强大的抗肿瘤功效。
