<i>Lycium barbarum</i> Polysaccharide-Stabilized Selenium Nanoparticles Deliver Triptolide to Induce Apoptosis for Pancreatic Cancer <i>In Vitro</i> and <i>In Vivo</i>

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 <i>Tripterygium wilfordii</i>, shows promising antitumor activity. However, the systemic toxicity and poor water solubility of TP inhibit its clinical application. In this work, <i>Lycium barbarum</i> 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. <i>In vitro</i> 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 <i>in vitro</i> and <i>in vivo</i>. 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.