OximUNO treatment reduces primary tumor growth and pulmonary metastases and alleviates immunosuppression. Treatment with OximUNO, St-PGA-DOX, or DOX at 2 mg/kg of DOX in mice bearing orthotopic TNBC tumors (N = 5). Intraperitoneal injections began when tumors reached 25 mm³ and were performed every other day to give a total of nine injections. A, Primary tumor volume progression during treatment. Orange arrows indicate injection days. B, Primary tumor weight at the experimental endpoint, demonstrating a significantly smaller weight for OximUNO-treated mice (red bar) than other groups. C, Mouse bodyweight analysis suggests the safety of OximUNO treatment (red line); meanwhile, DOX treatment induced a significant reduction in bodyweight by the experimental endpoint (purple line). Dark gray ∗ DOX versus PBS, orange ∗ DOX versus St-PGA-DOX. D, Representative H&E images showing spontaneous pulmonary metastases for all groups (scale bars = 400 μm); OximUNO treatment associated with the smallest metastatic area (E) and the lowest number of average nodules per lung (F). G, Representative images showing the expression of CD31 and blood vessels in primary tumors. H, Graph depicting the expression of CD31 in primary tumors. I, Graph depicting the CD31⁺ blood vessel count in primary tumors. CD31 expression and blood vessel count were calculated using ImageJ and five images per mouse per group for expression analysis and at least three images per mouse per group for blood vessel count. Representative confocal microscopy images and quantification graphs of primary tumors demonstrating the expression of CD206 (J and K), CD8 (L and M), and FOXP3 (N and O). Scale bars = 50 μm. P, Graph of CD8/FOXP3 expression ratio showing a shift in the immune profile. Quantification was performed using the ImageJ from at least three images per mouse and 5 mice per group. Error bars represent SEM. *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; n.s., > 0.05.