PDF(Pubmed)
Abstract：
Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single-atom manganese (Mn)-N/C nanozyme is constructed. Mn-N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing analysis reveals that Mn-N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn-N/C collectively activates the cGAS-STING pathway, subsequently stimulating type I IFN induction. A highly efficient single-atom nanozyme, Mn-N/C, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with the anti-PD-L1 blockade, is proposed.
摘要：
肿瘤微环境（TME）诱导的纳米催化疗法是一种有前途的癌症治疗策略。但低催化效率限制了其治疗效果。单原子催化剂（SAC）是一种新型的纳米酶，具有令人难以置信的催化效率。这里,构建了单原子锰（Mn）-N/C纳米酶。Mn-N/C通过类Fenton反应催化细胞H2O2转化为OH，并能够充分产生活性氧（ROS），它诱导肿瘤细胞的免疫原性细胞死亡（ICD）并显着促进CD8T抗肿瘤免疫。此外，RNA测序分析显示，Mn-N/C处理激活I型干扰素（IFN）信号，这对于Mn-N/C介导的抗肿瘤免疫应答至关重要。机械上,Mn-N/C触发的胞浆DNA和Mn2+的释放共同激活了cGAS-STING途径，随后刺激I型IFN诱导。一种高效的单原子纳米酶，Mn-N/C,与抗PD-L1阻断联合增强抗肿瘤免疫反应并表现出协同治疗效果，是提议的。
