Using glutathione‐responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF‐β1 receptor, it is demonstrated that local inhibition of TGF‐β within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and αPD1 therapy, and induces long‐term antitumor memory. Here, TGFB1 is linked to familial pancreatic carcinoma.