Cellular Responses to Nanoceria-Protein Corona Complexes: An Implication to Antioxidant Therapeutic Efficacy

Free radicals, including reactive oxygen species (ROS) have been implicated to the pathogenesis of various human diseases, such as cancer, chronic inflammation, neurodegenerative disorders, ophthalmologic conditions and even bacterial and viral infectious diseases. Quite recently, development of nano cerium oxide (ceria)-based ROS neutralising therapeutics has received escalating expectation due to the particle intrinsic Ce3+/Ce4+ switchable property. The redox cycling facilitates reversible storing and release of oxygen, which renders ceria as potential self-regenerating ROS scavenger in biological systems (Lord et al., 2012; Ting et al., 2013; Lord et al., 2013).

Upon administration of nanoceria into the bloodstream, the surfaces of the particles are immediately decorated with plasma proteins, forming a protein corona. The cells ‘see’ and interact with the nanoceria-protein corona complexes rather than just with the ‘bare’ nanoceria. The project seeks to investigate the effects of the particle physicochemical properties (size and presence of surface functional group) on the formation and dynamic nature of protein corona. Changes in the identity and composition of the protein corona will significantly influence the cellular responses to nanoceria, affecting cellular uptake, intracellular fates as well as ROS neutralising activity of nanoceria. Knowledge of the characteristics of the protein corona and the corresponding cellular responses will be used in the rational design and fabrication of nanoceria. In other words, to tune the surface properties of nanoceria for preferential binding of specific protein groups, to achieve cell-specific targeting and uptake as well as longer in vivo circulation time, and ultimately the optimal antioxidant therapeutic efficacy of nanoceria.

Cellular response

Upon uptake of nanoceria by human cells, the particles scavenge intracellular ROS (Ting et al., 2013)

Student undertaking this project will be working within the Particle and Catalysis Research Group and supervied by Prof Rose Amal and Dr Cindy Gunawan. The project is carried out in collaboration with the Graduate School of Biomedical Engineering (UNSW) and University of Technology Sydney (UTS). For more details, please contact Professor Rose Amal: r.amal@unsw.edu.au 

References

  1. Lord, M. S., Jung, M. S., Teoh, W. Y., Gunawan, C., Vassie, J., Amal, R., Whitelock, J. M. Biomaterials (2012) 33, 7915-7924.
  2. Ting, S. R. S., Whitelock, J. M., Tomic, R., Gunawan, C., Teoh, W. Y., Amal, R., Lord, M. S. Biomaterials (2013) 34 4377-4386.