title: Use of Synchrotron Radiation-Analytical Techniques To Reveal Chemical Origin of Silver-Nanoparticle Cytotoxicity.
abstract: To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information on intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectroscopy, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag(0))n, to Ag(+) ions and Ag-O-, then Ag-S- species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the present approach provides an integrated strategy capable of exploring the chemical origins of cytotoxicity in metallic nanoparticles.
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Tianlu
authors.initials: T
authors.lastname: Zhang
authors.affiliation: ‡Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Panyun
authors.initials: P
authors.lastname: Li
authors.affiliation: ‡Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wanxia
authors.initials: W
authors.lastname: Huang
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Tang
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Pengyang
authors.initials: P
authors.lastname: Wang
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: ‡Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Bai
authors.initials: B
authors.lastname: Li
authors.affiliation: ‡Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: †CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China and Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000737:chemistry* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000187:drug effects; D010316:Particle Size; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D017356:Synchrotrons; D014407:Tumor Cells, Cultured; D056928:X-Ray Absorption Spectroscopy; D014965:X-Rays
chemical_list: D003603:Cytotoxins; D012834:Silver
keywords: AgNPs; chemical origin; chemical transformation; dynamic processes of intracellular nanoparticles; nano-CT; nanotoxicity