Herein, the
vitamin K2 (VK2 )/
maleimide (MA) coloaded mesoporous
silica nanoparticles (MSNs), functional molecules including
folic acid (FA)/
triphenylphosphine (TPP)/tetrapotassium
hexacyanoferrate trihydrate (THT), as well as CaCO3 are explored to fabricate a core-shell-corona nanoparticle (VMMFTT C) for on-demand anti-
tumor immunotherapy. After application, the
tumor-specific acidic environment first decomposed CaCO3 corona, which significantly levitates the pH value of
tumor tissue to convert M2 type macrophage to the antitumor M1 type. The resulting VMMFTT would then internalize in both
tumor cells and macrophages via FA-assisted endocytosis and free endocytosis, respectively. These distinct processes generate different amount of VMMFTT in above two cells followed by 1) TPP-induced accumulation in the mitochondria, 2) THT-mediated effective capture of various signal
ions to cut off signal transmission and further inhibit
glutathione (GSH) generation, 3)
ions catalyzed
reactive oxygen species (ROS) production through Fenton reaction, 4) sustained release of VK2 and MA to further enhance the ROS production and GSH depletion, which caused significant apoptosis of
tumor cells and additional M2-to-M1 macrophage polarization via different processes of oxidative stress. Moreover, the primary
tumor apoptosis further matures surrounding immature dendritic cells and activates T cells to continuously promote the antitumor
immunotherapy.