Nanotechnology is increasingly having an influence on many aspects of our lives, including health care. Nanoparticles come in a wide range of shapes, sizes and compositions, with different formulations suiting different applications. They have proved to be very effective in a range of applications, with their use as drug delivery and imaging agents being particularly notable. The oral delivery of substances using nanoparticles has received comparatively little attention and their mode of action/delivery and toxicity are incompletely understood.
The focus of this project is to assess the mechanism of action/uptake and potential toxicity of two types of nanoparticles in the small intestine. The first will be a nanoparticle system developed to deliver iron and folate as dietary supplements. The second type of nanoparticle will be one designed to deliver cytotoxic drugs and chemoprotective agents for tumour therapy.
The nanoparticles themselves are currently being developed by collaborators in China. Our laboratory will assess their efficacy, mechanisms of action and toxicity. These will be examined initially in rat models, but the studies may be extended to strains of mice lacking critical components of intestinal transport pathways. Efficacy will be determined by measuring the delivery of the nanoparticle ‘cargo’ to the plasma and tissues, and by assessing nutrient status where appropriate (e.g. iron, folate levels). Light and electron microscopy will be used to follow the fate of the nanoparticles. Toxicity will be assessed morphologically and by measuring levels of oxidative stress in the gut. Since nanoparticles have the potential to alter gut microflora, 16S rRNA sequencing will be carried out to profile the gut microbiome before and after treatment. As part of these studies, a small intestine organoid culture system will be developed to enable the mechanism of nanoparticle interactions with the intestinal epithelium to be studied in greater detail. For example, inhibitors of membrane trafficking may be used in this system to determine whether they influence the interaction of the nanoparticles with the brush border membrane and/or their uptake into the cells.
Techniques to be used in this project include animal handling and phenotypic analysis, various types of microscopy, analysis of oxidative stress, microbiome analysis, and a range of more conventional biochemical, molecular and cell biology procedures.
- This project can be modified to suit Honours, PhD or Clinical students.