Endocytosis of nanomedicines: Dissecting the pathways of uptake of nanosized drug carriers by cells

Valentina Francia

Research output: ThesisThesis fully internal (DIV)

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Nanoparticles are small objects in the scale of nanometres (a billionth of a metre), used for a wide range of applications, including in nanomedicine, as new tools to deliver drugs to diseases. Even though several nanomedicines are currently in the market, in particular for cancer therapy, a clear understanding of how nano-sized materials are processed by cells is often still missing. Only with this knowledge it will be possible to fully exploit nanomedicine potential and design truly targeted nanomedicines. Recently it has emerged that the biological environment in which nanomedicines are dispersed influences remarkably their interactions with cells. In fact, once administrated intravenously, biomolecules present in the blood adsorb onto the nanomaterials, forming a corona layer that confers them a new biological identity.
Within this context, this thesis aims to characterize how nanomedicines are recognized and internalized by cells. We show that, depending on the serum content, the recognition of nanomedicines at the cell membrane can be mediated by specific cellular receptors interacting with corona proteins. Furthermore, the serum content and the resulting coronas also affect how these materials are internalized by cells. Next, we have optimized and combined different methods to characterize the mechanisms of uptake of nanomedicines, with a particular focus on the mechanisms of membrane curvature generation. We show that multiple mechanisms might be involved and curvature proteins also play a role. Finally, we show that the organization of cells into a barrier affects nanoparticle uptake, suggesting that more complex cell models should be used to characterize nanomedicines in the laboratory.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
  • Poelstra, Klaas, Supervisor
  • Salvati, Anna, Co-supervisor
Award date25-Sep-2018
Place of Publication[Groningen]
Print ISBNs78-94-034-1038-8
Electronic ISBNs978-94-034-1037-1
Publication statusPublished - 2018

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