Self-Assembled Tetrahedral Framework Nucleic Acid Mediated Tumor-Associated Macrophages Reprogramming and Enhancing Cancer Immunotherapy

There is increasing interest in depleting or repolarizing tumor-associated macrophages (TAMs) to generate a pro-inflammatory effect. However, TAMs usually display an immunosuppressive M2-like phenotype in tumor microenvironment. Apparently, developing a macrophage targeting delivery system with immunomodulatory agents is urgent. In the study, an efficient siRNAs and CpG ODNs delivery system (CpG-siRNA-tFNA) was prepared with nucleic acid stepwise self-assembled. The tFNA composed of CpG ODNs and siRNAs showed a higher stability and an enhanced cellular uptake efficiency. Moreover, the CpG-siRNA-tFNA effectively reprogrammed TAMs toward M1 phenotype polarization with increased pro-inflammatory cytokines secretion and NF-κB signal pathways activation, which triggers dramatical antitumor immune responses. Hence, we have developed an efficient and reliable TAM-targeted therapeutic with immunomodulatory agents for for clinical applications.