Herein, this study fabricates a cavitation-assisted ER-targeted sonodynamic droplets (PMPS NDs), achieving deep penetration and in situ sonodynamic therapy to enhance the effect of Anti-PD-L1 (aPD-L1) immunotherapy in orthotopic and distant pancreatic cancer (Scheme 1). The gene discussed is CD274; the disease is familial pancreatic carcinoma.