Electronic S Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang 453007, China.
Henan Key Laboratory of Green Chemical Media and Reactions, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China.
Int J Mol Sci. 2023 Sep 11;24(18):13935. doi: 10.3390/ijms241813935.
Nanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME by producing reactive oxygen species (ROS), which lead to positive oxidative stress in tumor cells. Cyclic dinucleotide (2',3'-cGAMP), as a second messenger, exists in the TME and can regulate it to achieve antitumor activity. In this work, Co,N-doped carbon dots (CoNCDs) were used as a model nanozyme to evaluate the properties of the anti-tumor mechanism, and effective inhibition of S180 tumor was achieved. Based on CoNCDs' good biocompatibility and therapeutic effect on the tumor, we then introduced the cGAS-STING agonist, and the combination of the CoNCDs and STING agonist significantly inhibited tumor growth, and no significant systemic toxicity was observed. The combined system achieved the enhanced tumor synergistic immunotherapy through TME reprogramming via the peroxidase-like activity of the CoNCDs and cGAS-STING signaling pathway agonist synergistically. Our work provides not only a new effective way to reprogram TME in vivo, but also a promising synergic antitumor therapy strategy.
纳米酶和环鸟苷酸-腺苷酸合酶（cGAS）干扰素基因刺激物（STING）信号通路作为强大的细胞器，可以重塑肿瘤微环境（TME），提高癌症免疫治疗的疗效并克服耐药性。纳米酶通过产生活性氧物种（ROS）来操纵 TME，从而导致肿瘤细胞发生阳性氧化应激。环二核苷酸（2'，3'-cGAMP）作为第二信使存在于 TME 中，可以调节 TME 以实现抗肿瘤活性。在这项工作中，我们使用 Co，N 共掺杂碳点（CoNCDs）作为模型纳米酶来评估抗肿瘤机制的特性，并实现了对 S180 肿瘤的有效抑制。基于 CoNCDs 对肿瘤良好的生物相容性和治疗效果，我们随后引入了 cGAS-STING 激动剂，CoNCDs 和 STING 激动剂的组合显著抑制了肿瘤生长，并且没有观察到明显的全身毒性。该联合系统通过 CoNCDs 的过氧化物酶样活性和 cGAS-STING 信号通路激动剂的协同作用，通过重编程 TME 实现了增强的肿瘤协同免疫治疗。我们的工作不仅提供了一种新的有效方法来在体内重编程 TME，而且还提供了一种有前途的协同抗肿瘤治疗策略。
