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 (SiO₂) and then coated manganese dioxide (MnO₂) to obtain GNRs@SiO₂@MnO₂ (GSM). Myeloid-derived suppressor cells (MDSCs) membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO₂@MnO₂@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 MnO₂ layer coating, realizing NIR-II window photothermal imaging and photoacoustic imaging of GSMM. Based on the release of Mn²⁺ in acidic TME, GSMM can be also used for magnetic resonance imaging. In cancer cells, Mn²⁺ catalyzes H₂O₂ 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.