In vivo tumor therapeutic effect of Cu-LDH/HMME@Lips on the 4T1 tumor-bearing mice. (a) Schematics of the establishment of 4T1 tumor-bearing mouse model and in vivo treatment process via tail vein injection at the same ZPF dose of 20 mg kg-1. (b) Time-dependent tumor volume change curves after various treatments and (c) the final tumor weight of mice in different groups. (d) Kaplan-Meier survival curves of 4T1 tumor-bearing mice in the different groups, during the whole 20 days of observation, no tumor reoccurrence has been observed in the mice of GOD/CAT@ZPF-Lips+US group. (e) Ex vivo immunofluorescence images of tumor sections, in which the nucleus and hypoxic regions were stained by DAPI (blue) and HIF-α antibody (green), respectively. (f) ROS fluorescence images of tumors after various treatments for 12 h. (g, h) Ki-67 immunofluorescence labeling and TUNEL staining of 4T1 tumor xenograft sections in 12 h posttreatments (scale bar: 100 μm). Scale bars in all groups are 100 μm.