Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics

The major hurdles of chemodynamic therapy (CDT) are nondegrad-ability and low-efficiency utilization of chemodynamic agents, and intracellular glutathione (GSH)-induced rapid scavenging of hydroxyl radicals (center dot OH). Here, a biodegradable a-CFT@IP6@BSA agent is reported for efficient cancer therapy by encapsulating amorphous copper iron tellurite nanoparticles (a-CFT NPs) into inositol hexaphosphate (IP6) and bovine serum albumin (BSA). The biggest merits of this agent are the GSH responsive degradation and amorphous structure, allowing the tumor-specific release of plenty of Cu+ ions and their high-efficiency utilization for center dot OH production via the Fenton-like reaction. Besides, the released Cu+ ions can deplete the intracellular GSH and thereby protect center dot OH from scavenging, greatly improving the CDT efficiency. Further, it is found that the a-CFT@IP6@BSA NP treatment down-regulates the levels of glutathione peroxidase 4 and BCL-2, indicating GSH depletion-associated ferroptosis and IP6-induced apoptotic death of cancer cells. Utilizing the T-1/ T-2 dual-modal magnetic resonance imaging capability, the a-CFT@IP6@BSA NPs are demonstrated with excellent in vivo anticancer efficiency and have great potential for imaging-guided cancer treatment.

Automated summary

In this study, a biodegradable a-CFT@IP6@BSA agent was developed for efficient cancer therapy. The agent can release plenty of Cu+ ions in a tumor-specific manner and utilize them for the production of hydroxyl radicals. It also depletes intracellular GSH to protect the hydroxyl radicals from scavenging. The treatment with a-CFT@IP6@BSA nanoparticles leads to the downregulation of glutathione peroxidase 4 and BCL-2, indicating the induction of ferroptosis and apoptotic death of cancer cells. The nanoparticles also demonstrate excellent anticancer efficiency in vivo and have the potential for imaging-guided cancer treatment.