Manganese-doped mesoporous polydopamine nanoagent for T1-T2 magnetic resonance imaging and tumor therapy

Theranostic nanodrugs combining magnetic resonance imaging (MRI) and cancer therapy have attracted extensive interest in cancer diagnosis and treatment. Herein, a manganese (Mn)-doped mesoporous polydopamine (Mn-MPDA) nanodrug incorporating the nitric oxide (NO) prodrug BNN6 and immune agonist R848 was developed. The nanodrug responded to the H⁺ and glutathione being enriched in tumor microenvironment to release R848 and Mn²⁺. The abundant Mn²⁺ produced through a Fenton-like reaction enabled a highly sensitive T1-T2 dual-mode MRI for monitoring the tumor accumulation process of the nanodrug, based on which an MRI-guided laser irradiation was achieved to trigger the NO gas therapy. Meanwhile, R848 induced the re-polarization of tumor-promoting M2-like macrophage to a tumoricidal M1 phenotype. Consequently, a potent synergistic antitumor effect was realized in mice bearing subcutaneous 4T1 breast cancer, which manifested the great promise of this multifunctional nanoplatform in cancer treatment.