The novel nanoparticles targeting folic receptor could efficiently and safely deliver pDNA encoding CKb11 and small molecular inhibitor that blocks PD-1/PD-L1 interactions to tumor sites and fight against cancer through remodeling the immunosuppressive TME by activating T lymphocytes, inhibiting macrophages towards type M2, and promoting DCs maturation in TME. The gene discussed is CD274; the disease is cancer.