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Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy

Bioactive Materials 2023年第1期19卷 237-250页

作者： Yuyue Zhao Yuanwei Pan Kelong Zou Zhou Lan Guowang Cheng Qiuying Mai Hao Cui Qianfang Meng Tongkai Chen Lang Rao Limin Ma Guangtao Yu Stomatological Hospital Southern Medical UniversityGuangzhou510280China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen518132China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore119074Singapore Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou510405China Medical Research Center Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou510080China

The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug targeting.Herein,an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed.Briefly,gold nanorods(GNRs)are covered with silica dioxide(SiO_(2))and then coated manganese dioxide(MnO_(2))to obtain GNRs@SiO_(2)@MnO_(2)(GSM).Myeloid-derived suppressor cells(MDSCs)membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO_(2)@MnO_(2)@MDSCs(GSMM).In this system,GSMM inherits active targeting TME capacity of MDSCs.The localized surface plasmon resonance of GNRs is developed in near-infraredⅡwindow by MnO_(2)layer coating,realizing NIR-Ⅱwindow photothermal imaging and photoacoustic imaging of GSMM.Based on the release of Mn^(2+)in acidic TME,GSMM can be also used for magnetic resonance imaging.In cancer cells,Mn^(2+)catalyzes H_(2)O_(2)into·OH for(chemodynamic therapy)CDT leading to activate cGAS-STING,but also directly acts on STING inducing secretion of typeⅠinterferons,pro-inflammatory cytokines and chemokines.Additionally,photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT,HMGB1 and ATP.In summary,our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.

关键词： Biomimetic manganese ions The second near-infrared window Cancer imaging Immunotherapy

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