Polypyrrole-iron phosphate-glucose oxidase-based nanocomposite with cascade catalytic capacity for tumor synergistic apoptosis-ferroptosis therapy.

• A novel PPy-FePO-GOx-PVA nanocomposite with cascade catalytic capacity was designed. • This nanocomposite can reshape tumor microenvironment through a cascade catalytic process. • This nanocomposite can generate abundant toxic·OH to drive tumor cells into ferroptosis pathway. • This nanocomposite can eliminate tumor effectively through the synergistic apoptosis-ferroptosis strategy. Utilizing the synergistic effect of apoptosis and ferroptosis for tumor elimination is a promising and effective strategy. Herein, a novel PPy-FePO-GOx-PVA nanocomposite with cascade catalytic capacity was designed and fabricated for tumor synergistic apoptosis-ferroptosis therapy. This nanocomposite was consisted of poly(vinyl alcohol)-stabilized polypyrrole (PPy-PVA) core, iron phosphate (FePO) payload, and glucose oxidase (GOx) decoration. The tumor microenvironment (TME) can be reshaped by this nanocomposite through a cascade catalytic process. Abundant gluconic acid and H 2 O 2 are generated in TME during the GOx-mediated glucose depletion process, which could promote the release of iron ions from FePO and elevate the efficiency of the consequent Fenton reaction. A mass of toxic ·OH was produced to oxidize lipids to lipid hydroperoxides, driving tumor cells into ferroptosis pathway. The redox reaction between Fe3+ ions and glutathione can provide Fe2+ ions, consume glutathione, and further inactive glutathione-dependent peroxidase 4, promoting the efficiency of ferroptosis by destroying redox balance. Furthermore, hyperthermia can be generated by PPy component under 1064 nm laser irradiation, causing tumor cell apoptosis. In vivo data reveal that effective tumor elimination is achieved by this PPy-FePO-GOx-PVA nanocomposite under laser irradiation through the synergistic apoptosis-ferroptosis strategy. [ABSTRACT FROM AUTHOR]