Anti-Tumor and Anti-Metastasis Effects of Berbamine-Loaded Lipid Nanoparticles on Pancreatic Cancer

Abstract

Objective: The aim of the study was 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 in 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 cell apoptosis. Moreover, the in vivo experiments revealed that compared to Free BBM, BBM-NPs exhibited a stronger inhibitory effect on the growth of xenograft tumors derived from PANC-1 cells in mice. In addition, increased expressions of ROS, Bax, Cleaved Caspase-3, and γ-H2AX, as well as decreased expressions of MMP2, MMP9 and Bcl-2 were identified in both Free BBM and BBM-NPs groups, while BBM-NPs exhibited a stronger effect on 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.

Keywords: Berbamine; anti-metastasis; anti-tumor; berbamine-loaded lipid nanoparticles; pancreatic cancer; tumor progression related proteins.