Abstract
Pancreatic cancer (PC), known as the ″king of cancer," is a prevalent and aggressive form of malignant tumor affecting the digestive tract. Triptolide (TP), an epoxidized diterpenoid lactone extracted from Tripterygium wilfordii, shows promising antitumor activity. However, the systemic toxicity and poor water solubility of TP inhibit its clinical application. In this work, Lycium barbarum polysaccharide (LBP)-modified selenium nanoparticles (SeNPs), capable of reducing severe toxicity and enhancing solubility, have been designed, synthesized, and applied for the treatment of PC. In vitro release results revealed that TP showed an acid-dependent and sustained-release effect. In Pan02 cells, the IC50 values of TP and LBP-SeNPs@TP were 26.03 ± 2.82 ng/mL and 11.80 ± 2.64 ng/mL, respectively. Similarly, the IC50 values of TP and LBP-SeNPs@TP for L02 cells were 15.76 ± 0.58 ng/mL and 32.73 ± 2.61 ng/mL, suggesting enhanced antitumor efficacy along with reduced toxicity. Flow cytometry analysis demonstrated that LBP-SeNPs@TP exerted the most potent apoptotic effect, achieving an early apoptosis rate of 24.5% and a late apoptosis rate of 45.3%. Notably, the mitochondrial membrane potential was significantly reduced, while ROS production was increased in the LBP-SeNPs@TP group. LBP-SeNPs@TP could significantly inhibit tumor growth while minimizing toxicity. RT-qPCR analysis demonstrated that LBP-SeNPs@TP upregulated the mRNA expression of Bax, Cyt C, and Caspase-3, while downregulating Bcl-2 expression in vitro and in vivo. The immunohistochemical analysis of the tumor tissue further confirmed these results. Overall, LBP-SeNPs emerge as a promising platform for poorly soluble drugs, offering a potential therapeutic approach for pancreatic cancer.