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Detonation nanodiamond toxicity is core and surface dependent
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.ORCID iD: 0000-0002-5510-2245
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Detonation nanodiamonds are carbon-containing nanoparticles that because of their small size, reactive surface and fluorescent properties are proposed for many applications, including biomedical such as imaging and drug delivery. The detonation synthesis produces impure nanodiamonds with contaminants such as soot and metals that can be reduced to some extent through various purification procedures. Based on early studies, detonation nanodiamonds have nevertheless been generally considered biocompatible. Toxicity of nanodiamonds has however been reported in several publications the last couple of years. Meanwhile, the number of suggested applications for nanodiamonds is rapidly increasing, hence underlining the importance of continuing with toxicity evaluations. Here, toxicity studies were performed on two model organisms, Escherichia coli and Zebrafish (Danio rerio) embryos. A range of commercially available detonation nanodiamond products from different manufacturers and of various purity grades were tested. The results show that some nanodiamonds are toxic and that the effect is independent of purity from soot and metals, but depend on the chemical composition of both the nanodiamond exterior and interior. Nanodiamonds with positively charged polyelectrolytes attached have a strong effect on the viability of cells and embryos. Based on our results we also suggest that toxicity might be correlated with nitrogen species, originating from the nanodiamond synthesis. Additionally, there is a strong correlation between the bacterial and vertebrate tests, meaning that the effect is not exclusively bactericidal.

National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-406619OAI: oai:DiVA.org:uu-406619DiVA, id: diva2:1417154
Available from: 2020-03-26 Created: 2020-03-26 Last updated: 2020-04-13
In thesis
1. Small Particles with Big Impact: Structural Studies of Viruses and Toxicological Studies of Nanodiamonds
Open this publication in new window or tab >>Small Particles with Big Impact: Structural Studies of Viruses and Toxicological Studies of Nanodiamonds
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nanoparticles (NPs) can be found everywhere and their existence has both beneficial and harmful consequences for the environment and living beings. The investigations on which this thesis is based upon have contributed to an increased understanding of some of these particles and to the development of a method that could be used to study their structure.

Three different NPs have been studied by different means. In the first study, I describe how single-particle cryo-electron microscopy was used to determine the atomic structure of an algal virus; Chaetoceros tenuissimus RNA virus type II. This virus is taxonomically classified in the order Picornavirales, which includes viruses that infect a wide range of organisms, including humans, plants and insects. By comparing the algal virus structure to structures of related viruses in the order, we could identify a number of traits that were likely acquired or lost among these viruses during the course of evolution. In the second study, rice dwarf virus was utilised as a test sample to develop a new structural biology method, single-particle coherent diffractive imaging (CDI). The method aims to study macromolecules in a single-particle fashion at room temperature with the help of an X-ray free-electron laser, thus enabling studies of fast dynamics without the need to crystallize or freeze the sample. The study was the first of several within a large international collaboration and the first single-particle CDI experiment reported using femtosecond hard X-ray pulses. Despite several advances by the team, many challenges remain for the method to reach its full potential. In the third study, I describe in vitro and in vivo toxicological studies of detonation nanodiamonds (DNDs). I could demonstrate that some DNDs are toxic and that the toxicity is dependent both on the core and surface of the particles. DNDs are suggested for numerous different biomedical applications that alternately utilise their toxic properties or require biocompatibility. The results presented show that these contrasting properties can be exhibited by similar DNDs and that thorough characterisation and close control of the manufacturing process is essential for biomedical applications.

This thesis explores how studies of some of nature’s nanoparticles - viruses - can lead to biological insight, how virus NPs can play a role in developing new technologies that may enable an even deeper understanding and explores issues that need to be considered for NPs to reach their potential in biomedical applications.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 93
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1929
Keywords
Chaetenuissarnavirus II, cryo-EM, CtenRNAV-II, Escherichia coli, Danio rerio, flash X-ray imaging, Marnaviridae, single-particle analysis, single-particle imaging, Sogarnavirus, virus evolution, virus structure, XFEL, zebrafish embryo
National Category
Biophysics Structural Biology
Research subject
Physics with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-406705 (URN)978-91-513-0933-0 (ISBN)
Public defence
2020-05-27, Room B8, Biomedicinskt centrum, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2020-05-06 Created: 2020-04-02 Last updated: 2020-05-06

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