Coordination Self-Assembled AuTPyP-Cu Metal–Organic Framework Nanosheets with pH/Ultrasound Dual-Responsiveness for Synergistically Triggering Cuproptosis-Augmented Chemotherapy

作者：Jianshuai Bao, Jiefei Wang, Su-Di Chen, Shiqi Liu, Zhen Wang, Weiwei Zhang, Chenhui Zhao, Yuling Sha, Xiaoyan Yang, Yusen Li, Yong Zhong, Feng Bai · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.3c13225 · 被引用次数：79 · 研究领域：Metal-Organic Frameworks: Synthesis and Applications、Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal–organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu 2+ ) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu 2+ was reduced to Cu + by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H 2 O 2 ) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI)...