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 Mn^(2+).The abundant Mn^(2+)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.