In the present study, we constructed a polymeric NP platform for steadily delivering CREBZF mRNA to BC cells in vivo, where CREBZF-mRNA-NPs successfully curbed proliferation and enhanced apoptosis of BC tumors by activating the positive feedback loop of CREBZF/STAT3/ADAR1/circPAPD4/miR-1269a. The gene discussed is CREBZF; the disease is breast cancer.