title: Assessing clinical prospects of silicon quantum dots: studies in mice and monkeys.
abstract: Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots.
authors.affiliation: Institute of Gerontology and Geriatrics, Chinese PLA General Hospital, Beijing 100853, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Liu
authors.forename: Folarin
authors.initials: F
authors.lastname: Erogbogbo
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Jinghui
authors.initials: J
authors.lastname: Yang
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Karker
authors.forename: Mark T
authors.initials: MT
authors.lastname: Swihart
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D000882:Haplorhini; D006801:Humans; D008099:Liver / Q000187:drug effects; D013058:Mass Spectrometry; D019216:Metals, Heavy / Q000737:chemistry; D051379:Mice; D023421:Models, Animal; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods; D010865:Pilot Projects; D020442:Poloxamer / Q000737:chemistry; D045663:Quantum Dots / Q000633:toxicity*; D012825:Silicon / Q000737:chemistry* / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects; D014018:Tissue Distribution; D018675:Toxicity Tests
chemical_list: D001672:Biocompatible Materials; D019216:Metals, Heavy; D020442:Poloxamer; D012825:Silicon