Synergetic effects and inhibition mechanisms of the polysaccharide‐selenium nanoparticle complex in human hepatocarcinoma cell proliferation

BACKGROUND Active components from natural fungal products have shown promising potential as anti‐tumor therapeutic agents. In the search for anti‐tumor agents, research to overcome the drawbacks of high molecular weight and low bioavailability of pure polysaccharides, polysaccharide‐conjugated selenium nanoparticles (SeNPs) has attracted much attention. RESULTS A novel polysaccharide‐selenium nanoparticle complex was produced, in which SeNPs were decorated with polysaccharide obtained from fermented mycelia broth of Lactarius deliciosus (FLDP). Transmission electron microscope, dynamic light scattering, and X‐ray photoelectron spectroscopy were utilized to characterize the FLDP‐SeNPs; and human hepatocarcinoma cell line (HepG2) was used to assess growth inhibition efficacy. The FLDP‐SeNPs that were prepared had a spherical shape with the smallest mean diameter of 32 nm. The FLDP‐SeNPs showed satisfactory dispersibility and stability after combination, demonstrating that a reliable consolidated structure had formed. The results revealed that FLDP‐SeNPs had notable growth inhibition effects on HepG2 cells. They reduced the membrane potential of mitochondria significantly, increased the generation of reactive oxygen species, enhanced levels of both Caspase‐3 and Caspase‐9, and led to the nucleus in a wrinkled form. CONCLUSION The FLDP‐SeNPs could exert a synergetic toxicity reduction and inhibition enhancement effect on HepG2 cells by inducing early apoptosis, through mitochondria‐mediated cytochrome C‐Caspases and reactive oxygen species‐induced DNA damage pathways. These results indicate that FLDP‐SeNP treatment of HepG2 cells induced early apoptosis with synergetic efficacy, showing that FLDP‐SeNPs can be useful as natural anti‐tumor agents. © 2024 Society of Chemical Industry.