title: In vivo toxicity evaluation of gold-dendrimer composite nanodevices with different surface charges.
abstract: Composite nanodevices (CNDs) are multifunctional nanomaterials with potential uses in cancer imaging and therapy. Poly(amidoamine) dendrimer-based composite nanodevices are important members of this group and consist of an organic dendrimer component and an incorporated inorganic component, in this case, gold. This study addresses the short- (14 days) and long-term (78 days) in vivo toxicity of generation-5 (G5; 5 nm) PAMAM dendrimer-based gold-CNDs (Au-CNDs) with varying surface charges (positive, negative and neutral) in C57BL/6J male mice. Detailed toxicological analyses of (1) body weight changes, (2) serum chemistry and (3) histopathological examination of 22 organs showed no evidence of organ injury or organ function compromise. Zeta potential of Au-CNDs showed significant change from their parent dendrimers upon gold incorporation, making the normally lethal positive surface dendrimer biologically safe. Also homeostatic mechanisms in vivo may compensate/repair toxic effects, something not seen with in vitro assays.
authors.affiliation: Department of Radiation Medicine, and joint appointment in the Department of Cell Stress Biology, The NanoBiotechnology Center at Roswell Park Cancer Institute-NBC at RPCI, Buffalo, NY, USA.
authors.forename: Venugopalan
authors.initials: V
authors.lastname: Kasturirangan
authors.forename: Bindu M
authors.initials: BM
authors.lastname: Nair
authors.forename: Muhammed T S
authors.initials: MT
authors.lastname: Kariapper
authors.forename: Wojciech G
authors.initials: WG
authors.lastname: Lesniak
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Remy
authors.initials: R
authors.lastname: Bizimungu
authors.forename: Peter
authors.initials: P
authors.lastname: Kanter
authors.forename: Karoly
authors.initials: K
authors.lastname: Toth
authors.forename: Sandra
authors.initials: S
authors.lastname: Buitrago
authors.forename: Youcef M
authors.initials: YM
authors.lastname: Rustum
authors.forename: Alan
authors.initials: A
authors.lastname: Hutson
authors.forename: Lajos P
authors.initials: LP
authors.lastname: Balogh
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Khan
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004563:Electrochemistry; D006046:Gold; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects; D013154:Spleen / Q000187:drug effects
chemical_list: D006046:Gold