Department of Mechanical and Aerospace Engineering, University of California, Davis, CA, 95616 USA.
Center for Health and the Environment, University of California, Davis, CA, 95616 USA.
Nanoscale. 2016 Jun 2;8(22):11518-30. doi: 10.1039/c6nr00897f.
Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 μg m(-3) of ∼30 nm europium doped gadolinium oxide nanoparticles (Gd2O3:Eu(3+)) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng per g body weight compared to 1.47 ng per g and 0.097 ng per g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution.
环境超细颗粒物(UPM),粒径小于 100nm,与肺部疾病的发生和恶化有关。对 UPM 的易感性的年龄差异可能是由于输送剂量的差异以及肺生物学和清除率的年龄依赖性差异。在这项研究中,我们开发并表征了含有镧系元素的新型金属氧化物纳米颗粒的气溶胶暴露,以研究新生大鼠肺部发育过程中的颗粒沉积。新生、幼鼠和成年大鼠(1、3 和 12 周龄)仅通过鼻腔暴露于 380μg/m3 的约 30nm 铕掺杂氧化钆纳米颗粒(Gd2O3:Eu(3+))1h。使用电感耦合等离子体质谱法确定鼻腔、肺外气道和肺部的沉积剂量。与成年和新生大鼠相比,幼鼠的沉积剂量明显更高,为 2.22ng/g 体重,而成年和新生大鼠分别为 1.47ng/g 和 0.097ng/g。通过定量回收的细胞类型以及测量乳酸脱氢酶活性和总蛋白,在支气管肺泡灌洗液(BALF)中研究了毒性。毒性数据表明,镧系颗粒没有急性毒性或炎症性,在任何年龄都没有增加中性粒细胞或乳酸脱氢酶活性。幼鼠和成年大鼠每克肺组织沉积的 NP 质量相同,而新生大鼠每克肺组织沉积的 NP 明显较少。本研究证明了新型镧系纳米颗粒在体内研究吸入颗粒沉积的实用性,并对作为治疗剂或作为部分颗粒物空气污染输送到发育中的肺部的纳米颗粒具有重要意义。