pH-responsive bromophenol blue/NH2-mPEGylated BSA@MnO2 nanoplatform for rectal cancer marking after neoadjuvant therapy

After neoadjuvant therapy (NT), precise localization of original tumor margins remains challenging. Here, we developed a pH-responsive BPB/NH2-mPEG-BSA@MnO2 (BBNPBMs) nanoplatform. BSA coating, NH 2 -mPEG modification, and BPB loading generated a (198.7 ± 5.43) nm composite structure, enabling long-term local retention, tumor microenvironment (TME) responsiveness, and synergistic naked-eye and MR visualization. BBNPBMs exhibited excellent dispersibility, stability, facile preparation and storage. Toxicological evaluation was favorable. Mn 2+ was primarily metabolized via liver, kidneys, and lymph nodes, and excreted in feces or urine. Under weakly acidic (pH 6.0–6.5) and oxidative conditions, MnO2 gradually degraded, continuously releasing paramagnetic Mn 2+ and enhancing T1-weighted MR signals. At 3.0 T, r1 and r2 reached 14.1 and 23.3 mM -1 s −1 , 3.34- and 4.41-fold higher than Magnevist® respectively, with imaging maintained > 30 days and visual marking > 90 days. Compared with carbon nanoparticle suspension injection (CNSI), BBNPBMs (200 μg/mL) showed a smaller diffusion area (1.38 ± 0.15 cm vs. 2.49 ± 0.40 cm, *P = 0.023). In summary, through the functional relationship of ‘pH response-gradual Mn 2+ release-visualization and long-term MR enhancement’, BBNPBMs meet localization requirements for 2–4 cycles of NT and demonstrate high translational potential.