Metal-based nanoparticles are clinically used for diagnostic and therapeutic applications. After parenteral administration, they will distribute throughout different organs. Quantification of their distribution within tissues in the 3D space, however, remains a challenge owing to the small particle diameter.

In this study, synchrotron radiation-based hard X-ray tomography (SRμCT) in absorption and phase contrast modes has been evaluated for the localization of superparamagnetic iron oxide nanoparticles (SPIONs) in soft tissues based on their electron density and X-ray attenuation. Biodistribution of SPIONs is studied using zebrafish embryos as a vertebrate screening model.

This label-free approach gives rise to an isotropic, 3D, direct space visualization of the entire 2.5 mm-long animal with a spatial resolution of around 2 µm. X-ray tomography is combined with physico-chemical characterization and cellular uptake studies to confirm the safety and effectiveness of protective SPION coatings.

It is demonstrated that SRμCT provides unprecedented insights into the zebrafish embryo anatomy and tissue distribution of labelfree metal oxide nanoparticles.


Zebrafish as a preclinical in vivo screening model for nanomedicines

Sieber S, Grossen P, Bussmann J, Campbell F, Kros A, Witzigmann D, Huwyler J.
Adv Drug Deliv Rev. 2019 Nov-Dec;151-152:152-168.
doi: 10.1016/j.addr.2019.01.001. Epub 2019 Jan 4. PMID: 30615917.

Optimization-by-design of hepatotropic lipid nanoparticles targeting the sodium-taurocholate cotransporting polypeptide

Witzigmann D, Uhl P, Sieber S, Kaufman C, Einfalt T, Schöneweis K, Grossen P, Buck J, Ni Y, Schenk SH, Hussner J, Meyer Zu Schwabedissen HE, Québatte G, Mier W, Urban S, Huwyler J.
Elife. 2019 Jul 23;8:e42276.
doi: 10.7554/eLife.42276. PMID: 31333191; PMCID: PMC6682401.

Preclinical Hazard Evaluation Strategy for Nanomedicines

Siegrist S, Cörek E, Detampel P, Sandström J, Wick P, Huwyler J.
Nanotoxicology. 2019;13(1):73-99.
doi:10.1080/17435390.2018.1505000. Epub 2018 Sep 5. PMID: 30182784.

Zebrafish as an early stage screening tool to study the systemic circulation of nanoparticulate drug delivery systems in vivo

Sieber S, Grossen P, Detampel P, Siegfried S, Witzigmann D, Huwyler J.
J Control Release. 2017 Oct 28;264:180-191.
doi: 10.1016/j.jconrel.2017.08.023. Epub 2017 Aug 26. PMID: 28851572.

Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake

Campbell F, Bos FL, Sieber S, Arias-Alpizar G, Koch BE, Huwyler J, Kros A, Bussmann J.
ACS Nano. 2018 Mar 27;12(3):2138-2150.
doi: 10.1021/acsnano.7b06995. Epub 2018 Jan 18. PMID: 29320626; PMCID: PMC5876619.

Biomimetic artificial organelles with in vitro and in vivo activity triggered by reduction in microenvironment

Einfalt T, Witzigmann D, Edlinger C, Sieber S, Goers R, Najer A, Spulber M, Onaca-Fischer O, Huwyler J, Palivan CG.
Nat Commun. 2018 Mar 19;9(1):1127.
doi: 10.1038/s41467-018-03560-x. PMID: 29555899; PMCID: PMC5859287.

Poly(Sarcosine) Surface Modification Imparts Stealth-Like Properties to Liposomes

Bleher S, Buck J, Muhl C, Sieber S, Barnert S, Witzigmann D, Huwyler J, Barz M, Süss R.
Small. 2019 Dec;15(50):e1904716.
doi: 10.1002/smll.201904716. Epub 2019 Nov 13. PMID: 31722126.

PDMS-b-PMOXA polymersomes for hepatocyte targeting and assessment of toxicity

Kiene K, Schenk SH, Porta F, Ernst A, Witzigmann D, Grossen P, Huwyler J.
Eur J Pharm Biopharm. 2017 Oct;119:322-332.
doi: 10.1016/j.ejpb.2017.07.002. Epub 2017 Jul 16. PMID: 28720487.

Immobilization of Enzymes on PLGA Sub-Micrometer Particles by Crosslinked Layer- by-Layer Deposition

Sieber S, Siegrist S, Schwarz S, Porta F, Schenk SH, Huwyler J.
Macromol Biosci. 2017 Aug;17(8).
doi: 10.1002/mabi.201700015. Epub 2017 Apr 7. PMID: 28388000.

DNA-directed arrangement of soft synthetic compartments and their behavior in vitro and in vivo

Liu J, Craciun I, Belluati A, Wu D, Sieber S, Einfalt T, Witzigmann D, Chami M, Huwyler J, Palivan CG.
Nanoscale. 2020 May 7;12(17):9786-9799.
doi: 10.1039/d0nr00361a. PMID: 32328600.

Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics

Einfalt T, Garni M, Witzigmann D, Sieber S, Baltisberger N, Huwyler J, Meier W, Palivan CG.
Adv Sci (Weinh). 2020 Jan 9;7(4):1901923.
doi: 10.1002/advs.201901923. PMID: 32099756; PMCID: PMC7029636.