Exploiting the Biomolecular Corona of Nanocarriers for Targeted drug Delivery to Endothelial Cells

Research output: ThesisThesis fully internal (DIV)

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Abstract

Since the past decades, nanoparticles have been extensively used as drug carriers and several nanomedicines are nowadays available in the market. Nevertheless, it is recognized that a better understanding of how nanoparticles overcome biological barriers can help to further improve nanomedicine efficacy. Among many biological barriers, the formation of a protein corona on the nanoparticles after administration and the need to target and cross specific endothelial cell barriers to reach the targeted tissue represent two critical aspects that can still limit nanomedicine effficacy.
Within this context, the aim of the thesis was to gain a better understanding of nanoparticle interactions with endothelial cell barriers, and at the same time, to exploit the protein corona as a tool to discover novel targeting strategies towards specific endothelial cell types. We show that the differentiation of endothelial cells into cell barriers affects nanoparticle uptake, suggesting the importance of using appropriate cell barrier models for in vitro testing. Furthermore, we found that endothelia of different organs showed different nanoparticle uptake efficiency, indicating that endothelial cell heterogeneity also affects nanoparticle uptake. Next, we used correlation analysis between the corona composition of different nanoparticles and their uptake efficiency in endothelial cells from different organs to identify corona proteins associated to increased or decreased uptake in the different endothelia. Finally, by using different methods based on corona proteomics, biotinylation, and nanoparticle uptake, we could identify (unique) cell receptors involved in nanoparticle uptake in brain and liver endothelium.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Salvati, Anna, Supervisor
  • Zuhorn, Inge, Supervisor
Award date5-Oct-2020
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-93184-58-9
DOIs
Publication statusPublished - 2020

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