title: Size and surface charge significantly influence the toxicity of silica and dendritic nanoparticles.
abstract: The influence of size, surface charge and surface functionality of poly(amido amine) dendrimers and silica nanoparticles (SNPs) on their toxicity was studied in immunocompetent mice. After systematic characterization of nanoparticles, they were administered to CD-1 (caesarean derived-1) mice to evaluate acute toxicity. A distinct trend in nanotoxicity based on surface charge and functional group was observed with dendrimers regardless of their size. Amine-terminated dendrimers were fatal at doses >10 mg/kg causing haematological complications such as disseminated intravascular coagulation-like manifestations whereas carboxyl- and hydroxyl-terminated dendrimers of similar sizes were tolerated at 50-fold higher doses. In contrast, larger SNPs were less tolerated than smaller SNPs irrespective of their surface functionality. These findings have important implications in the use of these nanoparticles for various biomedical applications.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
authors.forename: Giridhar
authors.initials: G
authors.lastname: Thiagarajan
authors.forename: Heather
authors.initials: H
authors.lastname: Herd
authors.forename: Robert
authors.initials: R
authors.lastname: Price
authors.forename: Hillevi
authors.initials: H
authors.lastname: Bauer
authors.forename: Dallin
authors.initials: D
authors.lastname: Hubbard
authors.forename: Alexander
authors.initials: A
authors.lastname: Burckle
authors.forename: Shraddha
authors.initials: S
authors.lastname: Sadekar
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.forename: Arnida
authors.initials: A
authors.lastname: Anwar
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry / Q000633:toxicity*; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000588:Amines; D001798:Blood Proteins; D050091:Dendrimers; C104700:PAMAM Starburst; D012822:Silicon Dioxide