title: Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration.
abstract: With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs (ζ potential = +46.5 mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs (ζ potential = -16.2 mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 µg/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs > Citrate AgNPs = PVP AgNPs > PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications.
authors.affiliation: a State Key Laboratory of Environmental Chemistry and Ecotoxicology, Chinese Academy of Sciences , Beijing , P.R. China .|b Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice , Venice , Italy .
authors.forename: Chengfang
authors.initials: C
authors.lastname: Pang
authors.affiliation: b Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice , Venice , Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunelli
authors.affiliation: a State Key Laboratory of Environmental Chemistry and Ecotoxicology, Chinese Academy of Sciences , Beijing , P.R. China .
authors.forename: Conghui
authors.initials: C
authors.lastname: Zhu
authors.affiliation: b Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice , Venice , Italy .
authors.forename: Danail
authors.initials: D
authors.lastname: Hristozov
authors.affiliation: c CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China , Beijing , P.R. China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: b Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice , Venice , Italy .
authors.forename: Elena
authors.initials: E
authors.lastname: Semenzin
authors.affiliation: d Department of Physics, Beihang University , Beijing , P.R. China , and.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Environmental Chemistry and Ecotoxicology, Chinese Academy of Sciences , Beijing , P.R. China .
authors.forename: Wuqun
authors.initials: W
authors.lastname: Tao
authors.affiliation: e Core Facility of Equipment, Institute of Microbiology, Chinese Academy of Sciences , Beijing , P.R. China.
authors.forename: Jingnan
authors.initials: J
authors.lastname: Liang
authors.affiliation: b Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice , Venice , Italy .
authors.forename: Antonio
authors.initials: A
authors.lastname: Marcomini
authors.affiliation: c CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology of China , Beijing , P.R. China .
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Environmental Chemistry and Ecotoxicology, Chinese Academy of Sciences , Beijing , P.R. China .
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D061605:Administration, Intravenous; D000327:Adsorption; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity*; D051379:Mice; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012834:Silver / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: C077842:polyvinylpolypyrrolidone; D012710:Serum Albumin, Bovine; D019343:Citric Acid; D012834:Silver; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D011205:Povidone
keywords: Acute toxicity; pharmacokinetics; protein sorption; surface coating