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)nanodr...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.展开更多
基金supported by the National Natural Science Foundation of China(Nos.51933011 and 31971296)the Key Areas Research and Development Program of Guangzhou(No.202007020006)+3 种基金Guangdong Basic and Applied Basic Research Foundation(No.2020A1515010523)Guangzhou Science and Technology Bureau(No.202102010181)Guangdong Provincial Key Laboratory of Sensing Technology and Biomedical Instrument(Sun Yat-sen University,No.2020B1212060077)approved by the Institutional Animal Care and Use Committee at Sun Yat-sen University(SYSU-IACUC-2021-000225).
文摘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.
