Early　diagnosis　of　pancreatic　ductal　adenocarcinoma　(PDAC)　is　challenging　because　of　its　depth,　which　often　leads　to　misdiagnosis　during　ultrasound　examinations.　The　unique　PDAC　tumor　microenvironment　(TME)　is　characterized　by　significant　fibrous　tissue　growth,　and　high　interstitial　pressure　hinders　drug　penetration　into　tumors.　Additionally,　hypoxia　and　immune　suppression　within　the　tumor　contribute　to　poor　responses　to　radiotherapy　and　chemotherapy,　ultimately　leading　to　an　unfavorable　prognosis.　In　this　study,　aPD-L1-modified　docetaxel　and　perfluoropentane-loaded　liquid‒vapor　phase-transformation　lipid　nanoparticles　(aPDL1-DTX/PFP@Lipid)　were　synthesized　and　had　an　average　diameter　of　61.63 nm　with　84.3%　antibody　modification.　We　demonstrated　that　the　nanoparticles　(NPs)　exhibited　excellent　PDAC-targeting　capabilities　both　in　vitro　and　in　vivo.　Upon　exposure　to　low-intensity　pulsed　ultrasound　(LIPUS)　stimulation,　the　NPs　underwent　a　phase　transformation　to　form　microbubbles　with　substantial　molecular　ultrasound　diagnostic　effects,　and　combined　treatment　resulted　in　a　tumor　growth　inhibition　rate　of　88.91%.　This　treatment　strategy　also　led　to　the　infiltration　of　CD8+　T　cells,　the　downregulation　of　Treg　cells,　the　promotion　of　M1　macrophage　polarization,　the　inhibition　of　fibrosis　to　reduce　tumor　stromal　pressure,　and　the　facilitation　of　perfluoropentane　(PFP)　gasification　to　release　O2　and　improve　tumor　hypoxia.　In　conclusion,　aPD-L1-modified　liquid‒vapor　phase-transformation　nanoparticles　loaded　with　docetaxel　(DTX)　and　PFP　were　successfully　combined　with　ultrasound　for　the　molecular　diagnosis　and　targeted　treatment　of　PDAC.　aPDL1-DTX/PFP@Lipid　could　reshape　the　PDAC　TME,　offering　a　new　approach　for　ultrasound-mediated　diagnosis　and　treatment　with　promising　clinical　applications.　©　The　Author(s)　2025.