Fabrication, Antiproliferative And Antioxidant Activities Of Selenium/tellurium Nanoparticles Functionalized By Saccharides

Due to the high bioavailability, low toxicity and outstanding anticancer activities,selenium nanoparticles (SeNPs) has become a new focus of scientific research.However, little information about the biological activities of tellurium nanoparticles(TeNPs) is available. In this dissertation, five kinds of Se/Te nanoparticlesfunctionalized with different saccharides have been fabricated in simple aqueoussystems. Furthermore, the in vitro anticancer activities, antioxidant activities andapoptotic signaling transduction pathways triggered by functionalized SeNPs/TeNPsin human cancer cells were also investigated in this study. The results include:1. By using mushroom polysaccharides-protein complexes (PTR or PRW) as thecapping agents, two types of size controllable and highly stable nanoparticlesPTR-SeNPs and PRW-SeNPs have been successfully fabricated under a simpleredox system of sodium selenite and ascorbic acid. The monodisperse andhomogeneous spherical PTR-SeNPs and PRW-SeNPs with appropriate particlesize (<100nm) kept stable in the solution phase for about1month under4℃.2. PTR or PRW surface decoration significantly enhanced the cellular uptake ofSeNPs through endocytosis detected by fluorescent technique. Treatment withPTR-SeNPs or PRW-SeNPs significantly inhibited the growth of MCF-7humanbreast carcinoma cells (IC50=3.70±0.06μM) and A549lung cancer cells (IC50=4.06±0.25μM) respectively through induction of apoptosis, with theinvolvement of caspase activation. Moreover, PTR-SeNPs not only induceddose-dependent depletion of mitochondrial membrane potential (ψm), but alsoenhanced reactive oxygen species (ROS) generation, indicating thatROS-mediated mitochondrial dysfunction may play an important role inPTR-SeNPs-induced apoptosis. In contrast, activation of death receptors wasfound as the main reason in PRW-SeNPs-induced apoptosis. In addition, G2/Mphase arrest was induced by PRW-SeNPs.3. By using glucose as the reductant and the capping agent, functionalized nanoparticles (Glu-SeNPs) with particle size at about280nm were fabricated bya simple hydrothermal synthesis method. HepG2liver cancer cells was foundsusceptible to Glu-SeNPs with IC50value of9.72±0.94μg/ml. The investigationon the underling mechanisms revealed that Glu-SeNPs inhibited HepG2growththrough induction of apoptosis, as evidenced by the increase in sub-G1cellpopulation, activation of caspase-3/-8/-9and disruption of ψm. Moreover, Sphase arrest was induced by Glu-SeNPs.4. Rodlike functionalized tellurium nanoparticles (PTR-TeNPs and Su-TeNPs) werecreated by using PTR or sucrose as the capping agents respectively in simplehydrothermal synthesis systems. The antioxidant activities of PTR-TeNPs andSu-TeNPs were evaluated by ABTS·+and DPPH free radical scavenging assay.The results indicated that PTR-TeNPs and Su-TeNPs exhibited strong antioxidantactivities by scavenging free radicals in a time-and dose-dependent manner.Preliminary studies showed that Su-TeNPs protected HK-2cells fromcisplatin-induced nephrotoxicity.5. MCF-7human breast carcinoma cells was found susceptible to PTR-TeNPs withIC50value of5.52±0.89μg/ml. The investigation on the underling mechanismsrevealed that PTR-TeNPs inhibited MCF-7growth through induction ofapoptosis supported by the increase in sub-G1cell population, activation ofcaspase-7/-9and disruption of ψm. Furthermore, TEM images of thin sectionsshowed mitochondrial damage in PTR-TeNPs-treated MCF-7cells. Takentogether, these results indicated that mitochondrial dysfunction may play animportant role in PTR-SeNPs-induced apoptosis.