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In the search for anti\u2010tumor agents, research to overcome the drawbacks of high molecular weight and low bioavailability of pure polysaccharides, polysaccharide\u2010conjugated selenium nanoparticles (SeNPs) has attracted much attention.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A novel polysaccharide\u2010selenium nanoparticle complex was produced, in which SeNPs were decorated with polysaccharide obtained from fermented mycelia broth of <jats:italic>Lactarius deliciosus<\/jats:italic> (FLDP). Transmission electron microscope, dynamic light scattering, and X\u2010ray photoelectron spectroscopy were utilized to characterize the FLDP\u2010SeNPs; and human hepatocarcinoma cell line (HepG2) was used to assess growth inhibition efficacy. The FLDP\u2010SeNPs that were prepared had a spherical shape with the smallest mean diameter of 32\u2009nm. The FLDP\u2010SeNPs showed satisfactory dispersibility and stability after combination, demonstrating that a reliable consolidated structure had formed. The results revealed that FLDP\u2010SeNPs 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\u20103 and Caspase\u20109, and led to the nucleus in a wrinkled form.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The FLDP\u2010SeNPs could exert a synergetic toxicity reduction and inhibition enhancement effect on HepG2 cells by inducing early apoptosis, through mitochondria\u2010mediated cytochrome C\u2010Caspases and reactive oxygen species\u2010induced DNA damage pathways. These results indicate that FLDP\u2010SeNP treatment of HepG2 cells induced early apoptosis with synergetic efficacy, showing that FLDP\u2010SeNPs can be useful as natural anti\u2010tumor agents. \u00a9 2024 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsfa.13335","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T07:18:51Z","timestamp":1706512731000},"page":"5124-5138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synergetic effects and inhibition mechanisms of the polysaccharide\u2010selenium nanoparticle complex in human hepatocarcinoma cell proliferation"],"prefix":"10.1002","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-2344","authenticated-orcid":false,"given":"Qingxi","family":"Wu","sequence":"first","affiliation":[{"name":"School of Life Sciences, Anhui University  Hefei PR China"},{"name":"Key Laboratory of 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