Through delivery of CSF‐1R siRNA by dual‐targeting nanoparticles, 52% of M2 TAMs were efficiently targeted and eliminated, resulting in an 87% decrease in tumor size and prolonged survival in a B16 melanoma mouse model.201 A similar strategy was developed by Tian and co‐workers who designed M2 TAM‐targeted peptide‐RNAi nanoparticles to silence VEGF mRNA in M2 TAMs.202 In addition, carcinoma‐associated fibroblasts (CAFs) are abundant in the TME and induce immunosuppression by releasing VEGF, IL‐6, IL‐10, and TGF‐β, while also preventing contact between cancer cells and cytotoxic T cells. The gene discussed is VEGFA; the disease is cancer.