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OBJECTIVE To investigate the therapeutic potential of Berbamine-loaded lipid nanoparticles (BBM-NPs) in pancreatic cancer. METHODS Dopamine polymerization-polylactide-TPGS nanoparticles were synthesized to prepare BBM-NPs, and the change of particle size of BBM-NPs was measured. Cell Counting Kit-8 (CCK8) assay, plate cloning experiment and apoptosis analysis were performed to evaluate the cytotoxicity of BBM-NPs against the pancreatic cancer cells (PANC-1 and AsPC-1). Migration and invasion abilities of the tumor cells were determined by Transwell and wound healing assays. The intracellular level of ROS and expression of tumor progression-related proteins were measured using ROS-kit and western blot assay. Besides, an in vivo study was performed in the Balb/c nude mice to analyze the function of BBM-NPs in tumor growth. RESULTS The in vitro studies showed that BBM-NPs with stable particle size and sustained drug release effectively inhibited the viability, proliferation, migration and invasion of pancreatic cancer cells, while promoting the cell apoptosis. Moreover, the in vivo experiments revealed that compared with Free BBM, BBM-NPs exhibited a stronger inhibitory effect on the growth of xenograft tumors derived from PANC-1 cells in the mice. In addition, increased expression of ROS, Bax, Cleaved Caspase-3, and γ-H2AX as well as decreased expression of MMP2, MMP9 and Bcl-2 were identified in both Free BBM and BBM-NPs groups, while BBM-NPs had a stronger effect on the protein expression than Free BBM. CONCLUSION In summary, BBM-loaded lipid nanoparticles enhanced the therapeutic effects of BBM on pancreatic cancer, providing a promising strategy for targeted cancer therapy.