title: Effects of nanoparticle size and gestational age on maternal biodistribution and toxicity of gold nanoparticles in pregnant mice.
abstract: Gold nanoparticles (GNPs) have considerable applications in biomedicine, such as in bio-sensing, bio-imaging, drug delivery and photothermal therapeutics. However, currently there are limited information regarding the impact of pregnancy on their biodistribution, elimination and toxicity. In this study, we investigated the biodistribution and potential toxic effects of different-sized GNPs (1.5, 4.5, 13, 30 and 70 nm in diameter) in non-pregnant and pregnant mice at different gestational ages (E5.5, 7.5, 9.5, 11.5 and 13.5). 5h after intravenous injection, GNPs exhibited size-dependent biodistribution profiles; however, regardless of size, no significant biodistribution changes were observed between non-pregnant and pregnant mice. Kinetic studies showed that 4.5 nm GNPs were primarily excreted through urine within 5h, whereas 30 nm GNPs had a more prolonged blood circulation time. No apparent toxic effects (e.g., increased mortality, altered behavior, reduced animal weight, abnormal organ morphology or reduced pregnancy duration) were observed with different-sized GNPs in pregnant mice. However, treatment with 30 nm GNPs induced mild emphysema-like changes in lungs of pregnant mice. These results indicated that the maternal biodistribution patterns of GNPs in pregnant mice depended on particle size, but not gestational age; organ-specific adverse effects may arise with treatment with some GNPs according to their size.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; Immunology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Du
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; School for Radiological & Interdisciplinary Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Cuiji
authors.initials: C
authors.lastname: Sun
authors.affiliation: Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Women's and Infant's Health, University of Western Australia, Perth, Western Australia, Australia. Electronic address: jeff.keelan@uwa.edu.au.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Keelan
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China. Electronic address: niegj@nanoctr.cn.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Nie
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008657:Metabolic Clearance Rate; D053768:Metal Nanoparticles; D051379:Mice; D050607:Organogold Compounds / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D010316:Particle Size; D011247:Pregnancy; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology; D018570:Risk Assessment; D014018:Tissue Distribution
chemical_list: D050607:Organogold Compounds
keywords: Biodistribution; Gold nanoparticles; Nanotoxicity; Pregnancy; Size effects