Cancer targeting functionality of cerium oxide-based nanoparticles
M.S. Lord
Graduate School of Biomedical Engineering, The University of New South Wales,
Sydney, NSW 2052, Australia.e: m.lord@unsw.edu.au
Cerium oxide nanoparticles (nanoceria) are non-cytotoxic in many cell types
and react catalytically with reactive oxygen species (ROS) providing intracellular antioxidant properties. Excessive production of ROS leading to oxidative stress is
considered one of the pathological processes in inflammatory diseases such as
cancer, rheumatoid arthritis and atherosclerosis.
Our work has characterised the uptake of nanoceria synthesised in the range of
3 – 94 nm [1] in diameter by flame spray pyrolysis in human colon, ovarian and
melanoma cancer cell lines. Confocal fluorescence microscopy and flow cytometry
indicated that these cell types internalised the different sized nanoceria and while the
major uptake mechanism was passive uptake, the endocytotic pathways were also
involved and size-dependent. Folate receptors are highly expressed on many cancer
cells, and we found that folic acid functionalised nanoceria significantly increased
uptake and the level of co-localisation with lysosomes compared to the nanoceria.
Heparin functionalisation also increased uptake into endothelial cells, while the level
of heparin functionalisation directed trafficking to the lysosomes. High levels of
heparin functionalisation inhibited ROS scavenging, trafficked nanoparticles to the
lysosomes and reduced cell proliferation which may find application in the control of
angiogenesis in cancer [2].
We are investigating the cell surface proteoglycan, chondroitin sulphate
proteoglycan 4 (CSPG4), as a drug delivery target as it has a restricted distribution in
normal tissues and elevated expression in putative cancer cells. CSPG4 promotes
cell growth, adhesion, motility and invasion, all of which contribute to the invasive and
metastatic behaviour of malignant cells. We have characterised the forms of CSPG4
in colon and melanoma cells lines and have found that antibodies against the protein
core inhibit cell adhesion and spreading in vitro. Nanoceria functionalised with a
CSPG4 antibody is able to reduce the viability of melanoma cells in vitro while we are
currently investigating uptake mechanisms of these nanoparticles and cancer cell
fate.
Together these fundamental studies demonstrate the potential of cerium oxide
nanoparticles as therapeutic agents themselves or as drug carriers. These data also
demonstrate that the activities of the nanoparticles can be tuned by size, surface
chemistry and cell type.
References
[1] M. S. Lord, M. Jung, W. Y. Teoh, C. Gunawan, J. A. Vassie, R. Amal, J. M.
Whitelock, Biomaterials. 33, 7915 (2012).
[2] M. S. Lord, B. Tsoi, C. Gunawan, W. Y. Teoh, R. Amal, J. M. Whitelock.
Biomaterials. 34, 8808 (2013)