Abstract
Dysregulation of iron metabolism is a common characteristic of cancer cells. The rapid proliferation of the tumour cells means that there is an increased dependence upon iron compared to healthy cells. Chelation of iron can be undertaken with a number of different compounds, however, simply lowering systemic iron levels to control tumour growth is not possible since iron is essential for cellular metabolism in the rest of the body. Nanoparticulate iron chelators could overcome this difficulty by targeting to the tumour either by the passive enhanced permeation and retention effect, or by targeting ligands on the surface. Nanoparticles were prepared from melanin, which is a naturally occurring pigment that is widely distributed within the body, but that can chelate iron. The prepared nanoparticles were shown to be ~220 nm, and could adsorb 16.45 mmoles iron/g melanin. The nanoparticles showed no affect on control fibroblast cells at a concentration of 200 μM, whereas the immortalised cancer cell lines showed at least 56% reduction in cell growth. At a concentration of 1 mM melanin nanoparticles the cell growth could be reduced by 99% compared to the control. The nanoparticles also show no significant haemotoxicity, even at concentration of 500 μM. Melanin nanoparticles are therefore a viable prospect for destroying cancer cells via iron starvation.
Highlights
Iron is a trace element, integrally involved in a variety of metabolic processes from the synthesis of DNA to electron transport that underpins the production of ATP
These processes are upregulated in cells with a highly proliferative profile, such as cancer cells, meaning that acquiring sufficient amounts of iron is a crucial requirement if these cells are to survive
While there is no direct evidence that iron chelation is responsible for cell death, we have shown that the melanin nanoparticles can effectively chelate iron (Fig. 3)
Summary
Iron is a trace element, integrally involved in a variety of metabolic processes from the synthesis of DNA to electron transport that underpins the production of ATP These processes are upregulated in cells with a highly proliferative profile, such as cancer cells, meaning that acquiring sufficient amounts of iron is a crucial requirement if these cells are to survive. Cancer cells exhibit an elevated dependence on iron when compared to healthy controls To fuel this ‘iron addiction’, a range of metabolic alterations may occur that enhance the levels of cellular iron [1]. Such changes that abet neoplastic growth are selected 181 Page 2 of 9. One approach is to use nanoparticles and to rely on the EPR (enhanced permeation and retention) effect, enabling the particles to passively accumulate within tumour cells, providing a simple method for producing selectivity of iron chelation [7]
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