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

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 [email protected] 2 @MnO 2 (GSM). Myeloid-derived suppressor cells (MDSCs) membrane is further camouflaged on the surface of GSM to obtain [email protected] 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-infrared II window by MnO 2 layer coating, realizing NIR-II window 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 type I interferons, 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.