Zhu Yanfei, Wang Nan, Zhang Hanjie, Ling Junhong, Omer A M, Yang Guocai, Ouyang Xiao-Kun, Mei Lin
School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, PR China; State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, PR China.
School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan 316022, PR China.
J Colloid Interface Sci. 2025 Dec;699(Pt 2):138301. doi: 10.1016/j.jcis.2025.138301. Epub 2025 Jun 28.
Overcoming the limitations of chemodynamic therapy (CDT), constrained by the transient nature and limited bioavailability of reactive oxygen species (ROS), this study proposes a synergistic strategy integrating CDT with immunotherapy. We engineered a multifunctional nanocarrier, HMSN-Met@HA-CuO₂, leveraging CuO to amplify intracellular ROS generation and induce cuproptosis. Concurrently, metformin (Met) releases nitric oxide (NO), which scavenges ROS to generate more stable reactive nitrogen species (RNS). These RNS elicit sustained and irreversible damage to lipids, proteins, and deoxyribonucleic acid (DNA), resulting in potent tumor cell cytotoxicity and activation of an antitumor immune response. This work demonstrates the potential of an autonomously driven conversion from oxygen radicals to nitrogen radicals, coupled with the enhanced combinatorial application of CDT and immunotherapy, significantly improving antitumor efficacy.
为克服受活性氧（ROS）的短暂性质和有限生物利用度限制的化学动力疗法（CDT）的局限性，本研究提出了一种将CDT与免疫疗法相结合的协同策略。我们设计了一种多功能纳米载体HMSN-Met@HA-CuO₂，利用CuO增强细胞内ROS生成并诱导铜死亡。同时，二甲双胍（Met）释放一氧化氮（NO），其清除ROS以生成更稳定的活性氮物种（RNS）。这些RNS对脂质、蛋白质和脱氧核糖核酸（DNA）造成持续且不可逆的损伤，导致强大的肿瘤细胞毒性并激活抗肿瘤免疫反应。这项工作证明了从氧自由基到氮自由基的自主驱动转化的潜力，以及CDT和免疫疗法增强的联合应用，显著提高了抗肿瘤疗效。
