Date

Monday 20 Apr 2026

Time

15:15 - 15:45

Location

BW018

Supervisor

Alexander Kros

2nd reviewer

Sylvestre Bonnet

Jury

Stephan Hacker

Chemotherapy has made great strides over the past few years, but many challenges remain. Particularly delivering therapeutic agents where desired. Lipid nanoparticle (LNP) based RNA delivery is a potential solution to this problem. But to unlock its full potential an improvement in LNP targeting is still needed. Inspired by other anti-cancer modalities, namely Photo-activated Chemotherapy which uses light to activate a prodrug into a cytotoxic drug. This research explores the synthesis of a light-activatable ruthenium-based metal complex to be incorporated into LNP formulation. Upon irradiation with light two ionizable lipid ligands would dissociate from the photo-activatable ruthenium complex and facilitate payload delivery through the endosomal escape pathway.

Originally, two novel ionizable lipids were designed for this project. These lipids were based on a pyridine headgroup that could be para or meta substituted. After several design iterations the decision was made to refocus on synthesizing the meta ionizable lipid (m-IL) variant. The m-IL ligand was successfully synthesized, and steps were taken to optimize the synthesis of m-IL. Afterwards a coordination of m-IL to the ruthenium complex, based around a RuII atom with the chelate N-([2,2'-bipyridin]-6-yl)-N-methyl-[2,2'-bipyridin]-6-amine, was attempted but unsuccessful. All of this shows that improvements of the purification steps are needed to continue on with the development of a novel light-activatable ruthenium-based metal complex.