Collectively, our study demonstrates that PFD@NGHP targets the TGF-β1-PD-L1 axis in a cascading manner, offering a promising clinical strategy to overcome the adaptive radioresistance of irradiated pancreatic ductal adenocarcinoma while providing a potential platform for translational nanomedicine evaluation. This evidence concerns the gene TGFB1 and pancreatic ductal adenocarcinoma.