Open-Source and Reduced-Expenditure Nanosystem with ROS Self-Amplification and Glutathione Depletion for Simultaneous Augmented Chemodynamic/Photodynamic Therapy

• Published in: ACS applied materials & interfaces Vol. 14; no. 18; pp. 20682 - 20692
• Main Authors: Chen, Miaomiao, Zhao, Shuju, Zhu, Jialong, Feng, Erting, Lv, Fangyuan, Chen, Wenlong, Lv, Shibo, Wu, Yingnan, Peng, Xiaojun, Song, Fengling
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 11-05-2022
• Subjects: Biological and Medical Applications of Materials and Interfaces; Cell Line, Tumor; Glutathione - chemistry; Health Expenditures; Hydrogen Peroxide - chemistry; Nanoparticles - chemistry; Photochemotherapy; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Reactive Oxygen Species; synergistic therapy; calcium peroxide; reactive oxygen species photodynamic therapy; chemodynamic therapy
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.2c01782

Reactive oxygen species (ROS)-induced cell apoptosis has emerged as an efficient strategy for cancer therapy. However, tumor hypoxia and insufficient amounts of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment are currently the main limitations of photodynamic therapy (PDT) and chemodynamic therapy (CDT). Moreover, the glutathione (GSH) scavenging effect on ROS further hinders the efficiency of ROS-mediated therapy. Here, a CaO2-based nanosystem (named as CF@CO@HC) with ROS self-amplification and GSH-depletion abilities was developed by a bottom-up approach. This hybrid nanoparticle consisted of a photosensitizer-doped calcium peroxide (CaO2) core (CaO2-FM), a hybrid organosilica framework (Cu-ONS) incorporated with Fenton reagents (Cu2+) and tetrasulfide groups, and a local hydrophobic cage (HC) shell. The photosensitizer was fluorescein derivative 4-FM with a thermally activated delayed fluorescence (TADF) property. The HC shell was built to protect the CaO2 and the photosensitizer from being attacked by water. Upon being internalized into cancer cells, the nanosystem was decomposed through the reduction reactions of Cu2+ and the tetrasulfide bond-doped silica shell by GSH, thus releasing Cu+ for Cu+-mediated CDT. Meanwhile, the exposed CaO2-FM can react with H2O to liberate photosensitizer 4-FM and generate H2O2 and O2 to overcome barriers in CDT and PDT. Thus, our study provided an open-source and reduced-expenditure strategy via GSH depletion and ROS self-amplification behaviors for ROS generation and significantly achieved an improved synergistic PDT/CDT for cancers.