Patra Chitta Ranjan, Abdel Moneim Soha S, Wang Enfeng, Dutta Shamit, Patra Sujata, Eshed Michal, Mukherjee Priyabrata, Gedanken Aharon, Shah Vijay H, Mukhopadhyay Debabrata
Department of Biochemistry and Molecular Biology, 200 First Street S.W, Guggenheim 1321A, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905, USA.
Toxicol Appl Pharmacol. 2009 Oct 1;240(1):88-98. doi: 10.1016/j.taap.2009.07.009. Epub 2009 Jul 17.
Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu(III)(OH)(3)] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mg kg(-1) day(-1)) and time dependent manner (8-60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice euthanized on days 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod-treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods.
镧系元素纳米颗粒和纳米棒因其分别对内皮细胞具有荧光特性和促血管生成特性,已在生物医学纳米技术的诊断和治疗应用中得到广泛应用。最近,我们证明了通过微波技术合成并经多种物理化学技术表征的氢氧化铕[Eu(III)(OH)(3)]纳米棒可作为促血管生成剂,为严重缺血性心脏/肢体疾病和周围缺血性疾病引入未来的治疗策略。这些无机纳米棒对内皮细胞的毒性得到了多种体外试验的支持。为了确定体内毒性,在7天的时间里,每天以剂量依赖性(1.25至125 mg kg(-1) day(-1))和时间依赖性方式(8 - 60天)通过腹腔注射(IP)将这些纳米棒给予小鼠。通过电感耦合等离子体质谱法(ICPMS)分析不同器官中铕元素的生物分布。短期(S - T)和长期(L - T)毒性研究(分别在第8天和第60天对小鼠实施安乐死以进行S - T和L - T研究)显示,除了肝酶略有升高外,血液血液学和血清临床化学指标均正常。对纳米棒处理的重要器官(肝脏、肾脏、脾脏和肺)进行组织学检查,结果显示无组织学变化或仅有轻微组织学变化,表明在较高剂量的纳米棒作用下有轻度毒性。