Enhanced ROS-mediated antitumor efficacy of mitochondrion-targeted SeNPs stabilized byPhylloporia fontanesiipolysaccharides

Selenium nanoparticles (SeNPs) have recently gained attention as a promising selenium source in recent years due to their high bioactivity and low toxicity. However, their limited water solubility and degradability significantly hinder their application. In this study, polysaccharides extracted from Phylloporia fontanesiae were employed to synthesize SeNPs PFP-0.25B-SeNPs. These nanoparticles demonstrated superior dispersibility and stability, characterized by a monodisperse, uniformly spherical structure with an average particle size of 118.7 ± 0.76 nm. In vitro cellular assays revealed that PFP-0.25B-SeNPs functionalized with coumarin-6 exhibited a concentration- and time-dependent cellular uptake, predominantly localizing within mitochondria. PFP-0.25B-SeNPs induced apoptosis in A549 cells by targeting the tumor cell mitochondria via the TP53/Bax/CASP9/CASP3 pathway, resulting in a decrease in mitochondrial membrane potential, an increase in reactive oxygen species (ROS) production, upregulation of TP53, caspase 3, and caspase 9 expression, and an elevated Bax/Bcl-2 ratio. In vivo experiments in zebrafish demonstrated that PFP-0.25B-SeNPs inhibited tumor cell proliferation and angiogenesis, suggesting their potential as a candidate for lung cancer treatment.