Study of tissue biodistribution of gold nanoparticles in a wild-type mouse model by means of ICP-MS

SCK•CEN Mentor

Daems Noami, ndaems@sckcen.be, +32 (0)14 33 21 09

Expert group

Radiobiology

SCK•CEN Co-mentor

Verlinden Bart, bverlind@sckcen.be, +32 (0)14 33 31 09

Introduction

In cancer radiotherapy, gold nanoparticles (AuNPs) have emerged as promising radiosensitizers, which accumulate in the tumor and are believed to increase the effectiveness of external beam radiotherapy by local production of reactive oxygen species (ROS) and secondary electrons upon irradiation. At UNamur, 5 nm gold nanoparticles coated with an organic shell of polyallylamine are produced by plasma vapour deposition (AuNPs@PPAA). The AuNPs@PPAA can be conjugated to anti-EGFR antibodies (Cetuximab) (mAb-AuNPs@PPAA) which actively target EGFR-overexpressing cancer cells in vitro and in vivo. However, in vivo biodistribution studies using mirco-PET imaging have demonstrated a significant accumulation in the liver and the spleen. Therefore, the cytotoxicity profile of the gold nanoparticles should be investigated properly in these healthy tissues prior to use the mAb-AuNPs@PPAA in clinical applications.

Objective

The aim of this study is to quantify the biodistribution of gold nanoparticles in a wild-type mouse model. mAb-AuNPs@PPAA will be injected in normal wild-type mice. Different time points after injection, the liver, spleen, lungs, brain, kidneys and the blood will be the main targets to be studied. The concentration of gold in these tissues will be analysed quantitatively by ICP-MS. The master student will develop and optimize the tissue digestion process and the operating parameters to create accurate and reproducible quantitative measurements. Furthermore, the student will learn how to construct an in vivo pharmacokinetic profile of the AuNP nanoconjugate.

This master thesis is a collaborative project with the Radiobiology and Radiochemistry groups of the Studiecentrum voor Kernenergie (SCK•CEN) at Mol (Belgium). The student is expected to carry out all of the experimental work at SCK•CEN. SCK•CEN can provide appropriate accommodation for the student if required.

The minimum diploma level of the candidate needs to be

Academic bachelor

The candidate needs to have a background in

Chemistry