The impact hypoxia on nanomedicine uptake and efflux in human breast cancer cells

  • William John Brownlee

Student thesis: Doctoral Thesis

Abstract

In women, breast cancer is the most frequently diagnosed neoplasm, with a recognised high mortality burden. Breast cancer cells adapt to the hypoxictumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cellphenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocytic uptake and specific intracellular trafficking (Chapter 1). The aim of this thesis was to examine the impact of hypoxia and simulated reperfusion on the in vitro uptake and release of nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal changes in the hypoxic circuit (e.g. HIF1α expression). The preconditioned cells were then dosed with nanoparticles for 45 or 180 minutes emulating nanomedicine access following tumor reperfusion.Hypoxic preconditioning significantly increased nanoparticle retention by up to 10% when compared to normoxic cultures (p
Date of Award11 Mar 2019
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsEPSRC (Engineering and Physical Sciences Research Council) & University of Strathclyde
SupervisorPhilipp Seib (Supervisor) & Clive Wilson (Supervisor)

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