Fig. 6

a Schematic illustrations of the construction of targeted cascade nanocatalyst (RG-Mn@H) for remodeling TME, the sequential cascade reactions mechanism of RG-Mn@H on the generation of H₂O₂ for controllable CO release, and MR imaging-monitored combinatorial therapy of breast cancer. b TEM image of RG-Mn@H. c Relaxivity fits of RG-Mn@H in PBS solutions (50 μM of H₂O₂, pH 5.0 or 7.4) with or without addition of glucose. d Glucose concentration and (e) Oxygen concentration plotted against time in different concentrations of RG-Mn@H solution with the addition of glucose (10 mM) and H₂O₂ (50 μM). f The change of H₂O₂ concentrations in the glucose solution (10 mM) with the addition of RG-Mn@H (50 or 100 μg/mL) and free GOD (20 μg/mL). g In vitro cumulative release of CO from RG-Mn@H at different pH values with different amounts of H₂O₂. h The release profile of Mn²⁺ from RG-Mn@H (3 mg/mL) in PBS solutions (pH 5.0 or 7.4) with or without addition of glucose (Glu) and H₂O₂. i ATP level in MDA-MB 231 cells after different treatments as indicated. ***P < 0.001. Error bars indicate standard deviation (n = 5). j The H₂O₂ level in MDA-MB-231 cells after different treatments ([Mn]: 10 μg/mL). k Quantitative results of the Akt-1, Nrf-2, and HMOX-1 expression after different treatments. **P < 0.01. Error bars indicate standard deviation (n = 3). l Intracellular CO level detected by using COP-1 CO fluorescence probe ([Mn]: 10 μg/mL). Fluorescence images of MDA-MB-231 cells after different treatments and stained with (m) intracellular DCFH-DA probe and (n) JC-1 dye (red, aggregates; green, monomers). o In vivo T₁-weighted MR images of the tumor bearing mice at different time points after i.v. injection of RG-Mn@H (Mn: 5 mg/kg, tumors are indicated by the red rings). p The tumor growth curves during different treatments (n = 5). Reproduced with permission from Ref. [129]. Copyright 2021, Elsevier Inc.