Elemental Selenium Nanoparticles Size-dependently Suppress Hepatocarcinoma Cell Proliferation In Mice

Selenium (Se) has anti-cancer activities whose mechanisms involve Se-dependentselenoproteins, Se-induced Phase2enzymes and Se-mediated cytotoxicity. The biologicalactivity and toxicity of selenium are associated with chemical form. Selenium in the redoxstate of zero, i.e. elemental selenium, is biologically inert which is neither active nor toxic.Red elemental selenium, formed in the redox system of sodium selenite and glutathione, isunstable and can further aggregate into gray or black elemental selenium. Protein such asBovine Serum Albumin (BSA) existing in the redox system can control the aggregation ofred elemental selenium; the resultant red elemental selenium particles are stable and atnano sizes which under200nm, thereby being designated as Nano-Se. Preliminary studieshave demonstrated that compared with sodium selenite, Nano-Se have loweracute toxicityand similar bioavailability. Furthermore，there is size effect in scavenging free radicals.These results challenges the long-held dogma that selenium in the redox state of zero isbiologically inert.The size-dependent in vivo bioactivities of elemental Se nanoparticles are notstraightforward, we have demonstrated that Se nanoparticles can size-dependently increasePhase2enzyme activity at supranutritional dose levels, unexpectedly there is no size effectin increasing selenoproteins at nutritional dose levels. In vivo cytotoxic activity of Senanoparticles has never been elucidated, let alone the size effect. The present workinvestigated the impact of Se nanoparticles on H22hepatocarcinoma cell proliferation inmice ascitic fluid. Se nanoparticles were able to profoundly suppress H22cell proliferationwithout perceived toxicity; the proliferation suppression efficacy largely relied on particledimension with smaller size being more potent. Se nanoparticles could be reduced byglutathione into liquid Se metabolites in a strictly size-associated fashion with smaller sizebeing more efficient and gaseous Se metabolites which have not such characteristics. Theprofile of predominant liquid Se and minor gaseous Se seen from smaller sized Senanoparticles subjected to glutathione reduction could also be observed from the reactionof sodium selenite and glutathione. Consequently, selenite exhibited strong proliferationsuppression potency as seen in smaller sized Se nanoparticles. Thus the size-dependentproliferation suppression is likely associated with the size-dependent formations of liquidSe metabolites. In conclusion, Se nanoparticles should be most effective for exertingcytotoxic functions at smaller size.