a Trauma Center, Shanghai General Hospital of Nanjing Medical University , Shanghai , P.R. China.
b Trauma Center, Shanghai General Hospital , Shanghai Jiaotong University School of Medicine , Shanghai , P.R. China.
Artif Cells Nanomed Biotechnol. 2018;46(sup2):112-121. doi: 10.1080/21691401.2018.1452250. Epub 2018 Mar 23.
Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO. And Se@SiO has few interference to the therapeutic effect of DOX. Particularly, Se@SiO significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO nanocomposite in the clinical use of DOX.
多柔比星（DOX）是一种有效的抗癌药物，广泛用于临床治疗。然而，其严重的心脏毒性限制了其应用。因此，减轻 DOX 的毒性而不影响其疗效是当务之急。许多研究表明，硒可能保护正常组织免受某些抗癌药物的损害。最近，硒@二氧化硅纳米复合材料因其理想的生物相容性而成为治疗癌细胞的直接元素硒的更好替代品。在本文中，我们合成了硒@二氧化硅纳米复合材料，并根据以往的研究对其进行了特性鉴定。我们将硒@二氧化硅纳米复合材料与 DOX 联合使用，然后探索了这种联合用药的毒性和疗效。在体内实验中，硒@二氧化硅显著提高了 DOX 处理的小鼠的存活率。并且，硒@二氧化硅对 DOX 的治疗效果干扰很小。特别地，硒@二氧化硅显著减轻了 DOX 诱导的心肌组织损伤（血清指标、细胞凋亡指标、western blot 指标），并保护了 DOX 处理的小鼠的 LVEF 降低。综上所述，我们得出结论，硒@二氧化硅在 DOX 诱导的心脏毒性中的保护作用可能归因于其对 ROS 生成的抑制作用，这表明硒@二氧化硅纳米复合材料在 DOX 的临床应用中具有很大的潜力。
