H2O2 self-supplying Ce6@ZIF-8/PDA/CuO2/HA (CZPCH) nanoplatform for enhanced reactive oxygen species (ROS)-mediated tumor therapy

Tumor hypoxia, limited H 2 O 2 levels, and abundant glutathione (GSH) in the tumor microenvironment (TME) pose challenges for high-efficiency reactive oxygen species (ROS)-mediated therapies. To address these limitations, an intelligent ROS-mediated nanoplatform, Ce6@ZIF-8/PDA/CuO 2 /HA (CZPCH), with photodynamic activity, self-supplied H 2 O 2 , Fenton-like reaction, GSH-depletion and photothermal activity was designed for efficient tumor treatment. In the acidic TME, CuO 2 in CZPCH deposits into Cu 2+ and H 2 O 2 , consuming GSH and triggering Fenton-like reactions to generate hydroxyl radical (•OH), enabling efficient chemodynamic therapy (CDT). Moreover, the presence of Ce6 and PDA enables CZPCH to exhibit excellent singlet oxygen ( 1 O 2 ) and temperature increase performance 660 nm and 808 nm laser irradiation, respectively, resulting in efficient photodynamic therapy (PDT) and photothermal therapy (PTT) efficacy. Interestingly, the temperature increase from PTT significantly enhances •OH and 1 O 2 generation, achieving high-efficiency ROS-based therapeutic efficacy. This synergistic CDT/PDT/PTT treatment demonstrates excellent anti-tumor efficacy and illuminates novel ROS-based therapeutic strategy design.