Synthesis, characterization, and anticancer activity of protamine sulfate stabilized selenium nanoparticles

Selenium nanoparticles (SeNPs) have attracted much recent interest as nutraceuticals, while they face great challenges, such as poor stability and low cellular uptake efficiency. This study introduced a facile approach to synthesizing protamine sulfate (PS) functionalized selenium nanoparticles (PS-SeNPs) by using PS as a surface decorator. The monodisperse spherical PS-SeNPs with a particle size of 130 nm and a ζ-potential of +31 mV were ligated with PS through Se-N, Se-O bonds, and physical adsorption, which exhibits excellent physical stability against pH, temperature, and storage time. The positive surface charge of PS-SeNPs contributed to the enhancement of cellular uptake efficiency by endocytosis, which was 3-times higher than bare SeNPs. Compared to SeNPs (IC 50  = 17.675 μg/mL), PS-SeNPs could dramatically inhibit the proliferation of HepG2 cells with an IC 50 value of 5.507 μg/mL, as reflected by the induction of apoptosis, S phase arresting, overproduction of intracellular ROS, and depolarization of mitochondria membrane. Overall, these results demonstrated the great potential of PS-SeNPs that can be applied as a functional ingredient in foods and nutraceuticals.