Natural melanin nanoparticles for photothermal therapy: A comparative study of metal ion-chelated and non-chelated forms

Melanin nanoparticles (MNPs) chelated with metal ions have attracted increasing interest for theranostic applications. However, the effect of metal ion chelation on the photothermal therapy (PTT) performance of MNPs remains largely unexplored. This study investigates the PTT potential of melanin-based nanoparticles (MBNPs), focusing on the effects of irradiation wavelength and iron chelation. MNPs and Fe3+- chelated melanin nanoparticles (MNP-Fe3+) were synthesized and applied to prostate cancer cells. First, a cytotoxicity assay was performed to identify the highest non-toxic concentrations of the nanoparticles. Fe3+-chelated MNPs showed reduced cytotoxicity, indicating that melanin may mitigate the toxic effects of Fe3+ ions, which is an advan tageous property for their use as contrast agents in magnetic resonance imaging (MRI). Given the broad absorption spectrum of MBNPs spanning 200-800 nm, three distinct wavelengths (530 nm, 660 nm, and 785 nm) were selected to use in PTT experiments. Among the tested wavelengths, only irradiation at 785 nm led to a significant reduction in cell viability. For the non-chelated MNPs, cell survival decreased to approximately 50% in the 20 min PTT group. For the MNP-Fe3+, the survival was reduced to around 40% in the 10 min PTT and further declined to about 30% following 20 min PTT treatment. Live/dead staining was performed solely for the 785 nm group, confirming the cell death patterns observed in the MTT assay. Therefore, our results showed that Fe3+ chelation enhanced the photothermal activity of MNPs. These findings suggest that Fe3+ chelation of MNPs, already known to enhance MRI contrast, also improves their biocompatibility and PTT efficacy