NANONIZATION OF MELANIN AND ITS APPLICATIONS TO BIOMEDICINE
Date Issued
2015
Date
2015
Author(s)
Liu, Yi-Cheng
Abstract
Melanin is one of the most ubiquitous heterogeneous biological polymer widespread in our body tissue. However, its complete molecular hierarchical structure is still unknown. Melanin has a broadband absorption spectrum and it can generate permanent and light-induced free radicals. In the human epidermis, melanocytes have numerous enzymes with capabilities in antimicrobial defense and functional links to the immune system, in which melanin may play an activating role. Furthermore, it is believed that melanocytes in the human epidermis play a key role in protecting our skin from the damaging effects of UV radiation by scavenging free radicals and reactive oxygen species, besides simply attenuating the radiation. It is well established that melanin has multiple functions such as anti-radiation, antioxidant, antitumor, antivenin, anti-virus, and removing heavy metal ions. In all these potential applications, insolubility of both natural melanin and synthetic melanin in bio-compatible solvent leads to quick precipitation and formation of large aggregates, drastically reducing the efficacy in in vivo and in vitro experiments. We deliberately set out to develop techniques based on photo-fragmentation with femtosecond laser pulses and mechanical smashing respectively for nanonization and dispersibilization of melanin, in order to more reliably study the biological functions of melanin and to promote the efficacy of melanin as medicine. It was found that both Sepia melanin and synthetic melanin particles processed with either method represent flaky shape with the diameter of ~42.5 nm and height of ~0.95 nm. Therefore, they can disperse in water and avoid precipitation for more than a week. In principle, the techniques can be applied to any kind of melanin. Amount them, the nanonization process by femtosecond laser pulses also serves as a top-down approach for resolving melanin structure. We inferred that in Sepia melanin the aggregation of nano-flakes is mediated by van der Waals interaction and hydrophobic interaction, whereas in synthetic melanin the formation of micro-flakes from nano-flakes is mediated by π–π interaction, which is substantially stronger than the former. As for the biomedical applications, experiments on the antimicrobial efficacy concluded that even if melanin plays a role in antimicrobial capability of skin, as proposed previously by others, it does not result from direct killing of microbe by melanin nanoparticle. In addition, this shows that melanin nanoparticle whether illuminated or not is not cytotoxic, therefore promises its use as medicine. Moreover, we demonstrated that nanonization dramatically improves the efficacy of melanin against acute oxidative stress and heavy metal ions. The effect was even more prominent without simultaneous light irradiation, promising for effective in vivo intravenous application to the whole body.
Subjects
melanin
femtosecond laser
electron paramagnetic resonance (EPR)
nano-medicine
nanoparticle
water-dispersible
reactive oxygen species
antioxidant
antimicrobial
metal ion
chelation
SDGs
Type
thesis
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