Glutathione/Cysteine Dual‐Consuming Prodrug Nanoassemblies for Potentiated Gas‐Photodynamic Therapy
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.
Authors
- Ning Tang (ORCID: https://orcid.org/0000-0003-2576-523X)
- Fan Tong (ORCID: https://orcid.org/0000-0002-4333-0128)
- Xie Xiaofang (ORCID: https://orcid.org/0000-0001-9892-1518)
- Pin-Yi Wu
- Hao Wang (ORCID: https://orcid.org/0000-0001-6052-0321)
- Xiaoyun Xing (ORCID: https://orcid.org/0000-0002-1045-1775)
- Lulu Wang (ORCID: https://orcid.org/0009-0009-1976-6333)
- Yang Zhou (ORCID: https://orcid.org/0009-0007-1638-8395)
- Chuan Hu (ORCID: https://orcid.org/0000-0002-8882-3276)
- Huile Gao (ORCID: https://orcid.org/0000-0002-5355-7238)
- Cheng Peng (ORCID: https://orcid.org/0000-0002-7406-8599)
- Miao Yu (ORCID: https://orcid.org/0000-0002-8708-1215)
- Honglei Wang (ORCID: https://orcid.org/0000-0001-6802-0102)
Institutions
- University of Electronic Science and Technology of China (CN)
- Hainan University (CN)
- Sichuan University (CN)
- Sichuan Cancer Hospital (CN)
- Chengdu University of Traditional Chinese Medicine (CN)
Publication Details
- Journal
- Advanced Functional Materials
- Published
- 2025-04-14
- DOI
- https://doi.org/10.1002/adfm.202503604
- Citations
- 5
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- National Natural Science Foundation of China