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.