Uptake, cellular fate and toxicity of engineered gold nanoparticles in A549 cells

Dosumu, Abiola Nneka (2018). Uptake, cellular fate and toxicity of engineered gold nanoparticles in A549 cells. University of Birmingham. Ph.D.

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Abstract

Engineered gold nanoparticles (AuNPs) can be modified to produce functionalized AuNPs with potential biomedical applications. However, prior to medical use, an understanding of cellular uptake and fate is critical to assess their potential toxicity.

This thesis studied 20 nm AuNPs coated with a luminescent ruthenium complex (RubySS) to fonn RubySS.AuNP, which were fully characterised prior to cellular studies in A549 cells treated for 2-72 hours.

The size of internalised particles as quantified by transmission electron microscopy (TEM) was in agreement with characterisation data of particles in solution and particle size remained unchanged after up to 72hours treatment indicating non-aggregation of internalised RubySS.AuNP. Particle number increased over time, and this was confinned by quantitative analysis of confocal images, TEM and inductively coupled plasma mass spectrometry.

Macropinocytosis and clathrin-mediated endocytosis were shown to be the route of uptake, with particles trafficked via the endo-lysosomal pathway as confirmed by co-localisation with fluorescent markers of early endosomes, lysosomes and autophagosomes in a time-dependent manner that, ultimately involved autophagy as confirmed by western blotting of LC3 protein.

Cellular accumulation of RubySS.AuNP also caused cellular changes related to oxidative stress including depletion of glutathione and DNA-strand breaks, but the mechanism of action remains to be elucidated.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):