Compared
to the activation of acquired immunity by the immune checkpoint
blockade, the activation of innate immunity via anti-phagocytosis
checkpoint blockade could significantly increase the beneficiary population
of immunotherapy. However, the activation of innate immunity and the
occurrence of phagocytosis are only accomplished when the interaction
between pro-phagocytosis signals and anti-phagocytosis signals is
realized. Herein, a versatile nanoplatform (DHMR) based on mesoporous
silicon nanoparticles (MSNPs) has been constructed. Two drugs, doxorubicin,
a chemotherapeutic drug which could initiate tumor cells to release
pro-phagocytosis signals, and RRx-001, an immunoadjuvant that could
effectively implement the anti-phagocytosis checkpoint blockade, were
loaded in MSNPs. Further decoration of hyaluronic acid encapsulation
endows DHMR with the function of tumor targeting and long circulation.
Ultimately, the DHMR system could efficiently and accurately target
tumor tissue, release the drugs in the tumor microenvironment, achieve
the activation of innate immunity, and finally dramatically inhibit
the growth and metastasis of tumor cells.