High Entropy 2D Layered Double Hydroxide Nanosheet Toward Cascaded Nanozyme-Initiated Chemodynamic and Immune Synergistic Therapy

作者：Chen Wang, Fengying Yuan, Zichao Yan, Tianqi Zhang, Chenchen Fu, Ya Li, Guidong Dai, Hyeong Seok Kim, Shuwei Xia, Liang Yu, Snehasish Debnath, Wen Xiu Ren, Jian Shu, Meng Qiu, Jong Seung Kim · 发表于：Journal of the American Chemical Society · 年份：2024 · DOI：10.1021/jacs.4c04523 · 被引用次数：90 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Extracellular vesicles in disease

High-entropy nanomaterials (HEMs) are a hot topic in the fields of energy and catalysis. However, in terms of promising biomedical applications, potential therapeutic studies involving HEMs are unprecedented. Herein, we demonstrated high entropy two-dimensional layered double hydroxide ( HE-LDH ) nanoplatforms with versatile physicochemical advantages that reprogram the tumor microenvironment (TME) and provide antitumor treatment via cascaded nanoenzyme-initiated chemodynamic and immune synergistic therapy. In response to the TME, the multifunctional HE-LDHs sequentially release metal ions, such as Co 2+, Fe 3+, and Cu 2+, exhibiting exquisite superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPX) activities. The multiple enzymatic activities convert specific tumor metabolites into a continuous supply of cytotoxic reactive oxygen species (ROS) to relieve hypoxia under a TME. Thus, HE-LDHs facilitate robust nanozyme-initiated chemodynamic therapy (NCDT), achieving high therapeutic efficacy without obvious side effects. In addition, the release of Zn 2+ from the HE-LDH matrix triggers the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling pathway, boosting the innate immunotherapeutic efficacy. The intratumoral applications of the nanocomposite in tumor-bearing mice models indicate that HE-LDH -mediated NCDT and immune synergistic therapy effectively upregulated the expression of relevant antitumor cytokines and induced cytotoxi...