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Assessing the safety of engineered nanoparticles designed for therapeutic use

Siegrist, Stefan Kevin. Assessing the safety of engineered nanoparticles designed for therapeutic use. 2017, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_13444

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Abstract

In 1959, physicist and Nobel laureate-to-be Richard Feynman held his famous speech “There’s Plenty of Room at the Bottom”. Herein he prophesized the upcoming of a new research field dedicated entirely to the nanometer scale. Six decades later we find ourselves amid the vision of Feynman where nanomaterials are omnipresent in daily life. Especially engineered nanoparticles (ENP) have gained enormous interest in medicine showing promising potentials as novel drug carrier systems, drug entities, and contrast agents. However, due to their size and physico-chemical properties, ENP inherit a unique toxicological profile that remains poorly understood. Moreover, the lack of generally accepted guidelines designed specifically for ENP prevents their proper safety regulation and risk assessment.
In collaboration with the Swiss Center for Applied Human Toxicology (SCAHT) and the Horizion2020 NanoReg2 consortium, we focused our research on establishing ENP-specific characterization strategies and assay toolboxes that should provide robust information on the safety of ENP-organism interactions.
Our results have shown that ENP toxicity is mediated by the chemical identity of a particle along with specific physico-chemical properties but also depends on the surrounding biological system. In vitro, in vivo, and in situ analyses ranging from simple viability studies to complex signaling pathway analysis have helped to link adverse effects and immune responses to different ENP types or specific properties thereof. Furthermore, we established the first protocol for the 3D-visualization of non-labeled ENP in vivo by synchrotron-radiation phase contrast x-ray micro-computer-tomography in therapeutically relevant dose-ranges. This novel method will aid to better understand the behavior of ENP after intravenous injection and may serve as a novel platform for the monitoring of ENP biodistribution and targeting.
Conclusively, the combined results obtained during this thesis have led to the proposal of a novel safety assessment strategy which specifically targets ENPs designed for therapeutic use. This proposal highlights the importance and the benefits of application-specific decision-making with a strong emphasis on physico-chemical characterization and in vitro hazard assessment. This strategy is meant to contribute to the ongoing establishment of much needed nano-specific safety guidelines and was developed to be in line with the interests of regulatory authorities and researchers alike.
Advisors:Huwyler, Jörg and Wilks, Martin
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Technologie (Huwyler)
UniBasel Contributors:Huwyler, Jörg
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13444
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (IX, 121 Seiten)
Language:English
Identification Number:
Last Modified:08 Feb 2020 15:12
Deposited On:11 Dec 2019 09:52

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