Glutathione/Cysteine Dual‐Consuming Prodrug Nanoassemblies for Potentiated Gas‐Photodynamic Therapy

作者：Ning Tang, Fan Tong, Pin-Yi Wu, Xie Xiaofang, Lulu Wang, Miao Yu, Xiaoyun Xing, Honglei Wang, Hao Wang, Huile Gao, Chuan Hu, Cheng Peng, Yang Zhou · 发表于：Advanced Functional Materials · 年份：2025 · DOI：10.1002/adfm.202503604 · 被引用次数：8 · 研究领域：Nanoplatforms for cancer theranostics、Photodynamic Therapy Research Studies、Sulfur Compounds in Biology

Abstract Tuning the oxidative stress‐defense system plays a vital role in the treatment of breast tumors. In this study, a pyropheophorbide‐a (PPa)‐based prodrug nanoassembly is constructed by linking PPa with furoxan, a cysteine‐depleting nitric oxide (NO) donor, through a disulfide bond. The as‐prepared prodrug (NOSP) can assemble with distearoyl phosphoethanolamine‐PEG 2000 (DSPE‐PEG 2000 ) to form nanoassemblies in aqueous media. Following internalization by tumor cells, NOSP can respond to cysteine (Cys) and induce NO release to activate endogenous matrix metalloproteinases (MMP‐1, ‐2), leading to collagen degradation and improved drug delivery. In addition, Cys consumption can impede the biosynthesis of glutathione (GSH), while NOSP can react with high levels of intracellular GSH within seconds, thus synergizing photodynamic therapy against breast tumors and distant metastasis.