Synthesis or preparation, physicochemical characterization, and H460 cell inhibition of selenium nanoparticles stabilized by Marsdenia tenacissima residue polysaccharide

In this study, a novel polysaccharide (TGT-S) was successfully extracted from the medicinal residue of Marsdenia tenacissima (Roxb.) Wight et Arn. To enhance its anti-lung cancer efficacy and exploit the therapeutic potential of selenium nanoparticles (SeNPs), we developed TGT-S-functionalized SeNPs (TGTs-SeNPs). The nanocomposites were systematically characterized in terms of size, morphology, structural features, colloidal stability, and thermal properties using multiple analytical techniques. Through response surface methodology optimization, TGTs-SeNPs with uniform spherical morphology and narrow size distribution were obtained, exhibiting an average particle size of 128.96 nm. The optimized synthesis parameters were established as follows: selenium-to-polysaccharide mass ratio of 1:5.483, selenium-to-ascorbic acid molar ratio of 1:4.213, selenite concentration of 9.474 mM, and reaction time of 4.175 h. The resulting TGTs-SeNPs demonstrated remarkable stability under physiological and alkaline conditions. The anti-cancer mechanism of TGTs-SeNPs (4.5–18 μg/mL) was elucidated in H460 lung cancer cells. The nanoparticles significantly inhibited cell proliferation by inducing S-phase cell cycle arrest and promoting apoptosis, as determined by flow cytometry. WB and RT-qPCR analysis further confirmed this dual mechanism, revealing downregulation of key cell cycle regulators (Cyclin A/D and CDK2/4) and activation of the mitochondrial apoptotic pathway, characterized by an increased Bax/Bcl-2 ratio and caspase-3 activation. This study not only presents a sustainable strategy for utilizing Marsdenia tenacissimaresidue but also highlights the promise of polysaccharide-based nanodrugs in cancer therapy.