Synergistic immunostimulation for tumor sensitization with a biomineralized DNA sponge

Abstract

The activation of stimulator of interferon genes (STING) plays a key role for provoking effective innate and adaptive immunity, yet is constrained by the limited clinical translation of STING agonists. Herein, we construct a smart DNA sponge to deliver STING agonists for robust cancer immunotherapy via the synergistic activation of innate immune pathways. The compact DNA sponge (Mn-CpG), assembling through a simple rolling circle amplification reaction, is encoded with numerous STING agonist (Mn2+) and toll-like receptor 9 (TLR9) agonist (CpG oligodeoxynucleotide) and allows their on-demand cellular delivery We show that Mn-CpG sponge can trigger the synergistic type I interferon response and robust T cell priming through a convenient coordination of different signaling pathways. In a poorly immunogenic breast cancer model, the method achieves the boosted immune responses with significantly inhibited tumor growth and metastasis.