Extracellular vesicles (EVs) are natural, biocompatible carriers with innate targeting abilities, making them promising drug delivery vehicles. However, as seen with most nanoparticle platforms, endosomal escape is a limiting factor for their therapeutic impact: the key step determining whether cargo,
e.g., CRISPR/Cas9 gene editing machinery, reaches the cytosol or is degraded. Overcoming this barrier is crucial to unlock the full potential of EVs as Advanced Therapy Medicinal Products (ATMPs).
Your jobA promising, yet unexplored, approach to the enhance endosomal escape efficiency of EVs is to engineer hybrid delivery systems by decorating their surfaces with synthetic polymers capable of selectively disrupting endosomal membranes.
In this PhD position your role will be to design and synthesize the polymers, devise strategies to tether them to EVs, and test the obtained hybrid delivery platforms for functional cargo delivery of model- and pharmaceutically relevant cargo
in vitro. Additionally, you will explore further functionalization of the hybrid EVs with nanobodies to improve their cellular uptake selectivity. In this research, you will be supported by existing expertise in EV isolation, loading and characterization (
Dr. de Jong), polymeric drug delivery systems (
Dr. van Ravensteijn) and nanobody-mediated targeting (
Dr. Oliveira). Ultimately, you will deliver a proof-of-concept for polymer-mediated endosomal escape of EVs, paving the way further
in vivo implementation.
The multidisciplinary nature and societal relevant research direction make this PhD position the ideal opportunity to develop yourself into an independent and versatile researcher which is well-versed in the latest developments in drug delivery. Additionally, you will have the chance to contribute to educating the next generation of (pharmaceutical) scientists through active involvement in the educational programmes of Utrecht University.