A metal ions-mediated natural small molecules carrier-free injectable hydrogel achieving laser-mediated photo-Fenton-like anticancer therapy by synergy apoptosis/cuproptosis/anti-inflammation

作者：Wenmin Pi, Linying Wu, Jihui Lu, Xiaoyu Lin, Xuemei Huang, Zhijia Wang, Zhihua Yuan, Hailing Qiu, Jianglan Zhang, Haimin Lei, Penglong Wang · 发表于：Bioactive Materials · 年份：2023 · DOI：10.1016/j.bioactmat.2023.06.018 · 被引用次数：94 · 研究领域：Natural Compounds in Disease Treatment、Beetle Biology and Toxicology Studies、Histone Deacetylase Inhibitors Research

Tumor microenvironment (TME) plays an important role in the tumorigenesis, proliferation, invasion and metastasis. Thereby developing synergistic anticancer strategies with multiple mechanisms are urgent. Copper is widely used in the treatment of tumor chemodynamic therapy (CDT) due to its excellent laser-mediated photo-Fenton-like reaction. Additionally, copper can induce cell death through cuproptosis, which is a new modality different from the known death mechanisms and has great promise in tumor treatment. Herein, we report a natural small molecules carrier-free injectable hydrogel (NCTD Gel) consisted of Cu2+-mediated self-assembled glycyrrhizic acid (GA) and norcantharidin (NCTD), which are mainly governed by coordination and hydrogen bonds. Under 808 nm laser irradiation, NCTD Gel can produce reactive oxygen species (ROS), consume glutathione (GSH) and overcome hypoxia in TME, leading to synergistically regulate TME via apoptosis, cuproptosis and anti-inflammation. In addition, NCTD Gel's CDT display high selectivity and good biocompatibility as it relies on the weak acidity and H2O2 overexpression of TME. Notably, NCTD Gel's components are originated from clinical agents and its preparation process is easy, green and economical, without any excipients. This study provides a new carrier-free hydrogel synergistic antitumor strategy, which has a good prospect in industrial production and clinical transformation.