Schematic illustration for MPN-HBP1-mediated anticancer therapy.

The PEI-HBP1 coordinates with tannic acid and ferric ions to form MPN-HBP1. After MPN-HBP1 nanoparticles reach the tumor site via passive targeting, the tannic acid and ferric ions in the MPN coating enhance the Fenton reaction to induce ferroptosis in tumor cells. Then, HBP1 transcriptionally inhibits the expression of the UHRF1 gene and down-regulates the level of UHRF1 protein. Reduced levels of UHRF1 are known to decrease the methylation level of the CDO1 promoter, promote the expression of CDO1 protein, and thus inhibit the production of GSH, promote the production of lipid peroxides, and induce ferroptosis. CDO1, cysteine dioxygenase 1; HBP1, HMG box-containing protein 1; MPN, metal polyphenol network; PEI, polyethyleneimine; UHRF1, ubiquitin-like with PHD and RING finger domains 1.