Bio-inspired melanin nanoparticles induce cancer cell death by iron adsorption

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.

Light- and Melanin Nanoparticle-Induced Cytotoxicity in Metastatic Cancer Cells

“…These suggest that a low glucose diet (e.g., ketogenic) for cancer therapies based on nanoparticles could be beneficial. Our results are in broad agreement with other reports on a variety of cancer cells [ 47 , 48 , 49 , 50 ].…”

Nanomaterials alleviating redox stress in neurological diseases: mechanisms and applications

“…Given that redox and non-redox metal ions can lead to the production of ROS and are involved in the pathology of neurological diseases, the removal of excess metal ions is a sensible therapeutic in oxidative stress-involved neurological diseases. Melanin NPs can chelate iron to impede the Fenton reaction and block the generation of ·OH in ischemic brains [ 5 , 144 ]. In addition, polymer- or inorganic-NPs-based nanocarriers loaded with natural prototype metal chelators have been tried for chelation therapy in neurological diseases.…”

Melanin and Melanin-Functionalized Nanoparticles as Promising Tools in Cancer Research—A Review

“…PDA also behaves as an antineoplastic system, selectively killing tumor cells without causing toxicity to healthy cells [ 97 , 137 ]. Perring et al showed that water-soluble melanin NPs induced selective cytotoxicity in human rhabdomyosarcoma (RH30, and RD) and glioblastoma (U-87 MG and Mo59K) tumor cell lines via iron deprivation, which is due to the chelating properties of melanin polymers [ 138 ]. In another study, Gabriele et al reported that highly monodispersed uncoated and glucose-coated MEL-NPs are massively absorbed by malignant cancer cells and influence their viability, which reduces with increasing numbers of absorbed NPs [ 139 ].…”