Figure 2.

(A) Schematic illustration of the fabrication of NP_MCA. (B) Fluorescence images of 4T1 cells in PBS-, NP_MC- and NP_MCA-treated groups without or with US treatment in the presence of ROS probes. (C) Immunofluorescence CRT staining images of 4T1 cells after different treatments. (D) MDA levels for 4T1 cells in PBS-, NP_MC- and NP_MCA-treated groups without or with US treatment. (E) Released ATP levels for 4T1 cells in various treatment groups. (F) Extracellular HMGB1 levels for 4T1 cells in PBS-, NP_MC- and NP_MCA-treated groups without or with US treatment. (G) Relative tumor volume of chicken breast tissue-covered 4T1 primary tumors in PBS-, NP_MC- and NP_MCA-treated mice without or with US treatment. (H) Relative tumor volume of 4T1 distant tumors in PBS-, NP_MC- and NP_MCA-treated mice without or with US treatment. (I) Total weight of primary and distant tumors in PBS-, NP_MC- and NP_MCA-treated mice without or with US treatment. (J) Tumor inhibition efficacy analysis. (K) Images of H&E stained primary and distant tumors in PBS-, NP_MC- and NP_MCA-treated mice without or with US treatment. The data are presented as the means ± SDs. The p values are calculated using two-tailed unpaired t test. *p < 0.05, **p < 0.01, and ***p < 0.001. Adapted from Zhan M, Wang F, Liu Y, et al. Dual-cascade activatable nanopotentiators reshaping adenosine metabolism for sono-chemodynamic-immunotherapy of deep tumors. Adv Sci. 2023;10(10):e2207200. Creative Commons.²⁰

Abbreviations: ADA, adenosine deaminase; Ce6, chlorin e6; NP_MCA, the nanopotentiator constructed through crosslinking ADA with Ce6-conjugated MnO₂ NPs via a ROS-cleavable linker; NP_MC, conjugating sonosensitizer Ce6 onto BSA-MnO₂ NPs; US, ultrasound; MDA, malondialdehyde.