Interactions of Melanin with Electromagnetic Radiation: From Fundamentals to Applications.

Melanin, especially integumentary melanin, interacts in numerous ways with electromagnetic radiation, leading to a set of critical functions, including radiation protection, UV-protection, pigmentary and structural color productions, and thermoregulation. By harnessing these functions, melanin and melanin-like materials can be widely applied to diverse applications with extraordinary performance. Here we provide a unified overview of the melanin family (all melanin and melanin-like materials) and their interactions with the complete electromagnetic radiation spectrum (X-ray, Gamma-ray, UV, visible, near-infrared), which until now has been absent from the literature and is needed to establish a solid fundamental base to facilitate their future investigation and development. We begin by discussing the chemistries and morphologies of both natural and artificial melanin, then the fundamentals of melanin-radiation interactions, and finally the exciting new developments in high-performance melanin-based functional materials that exploit these interactions. This Review provides both a comprehensive overview and a discussion of future perspectives for each subfield of melanin that will help direct the future development of melanin from both fundamental and applied perspectives.

Fossil insect eyes shed light on trilobite optics and the arthropod pigment screen.

Fossilized eyes permit inferences of the visual capacity of extinct arthropods1-3. However, structural and/or chemical modifications as a result of taphonomic and diagenetic processes can alter the original features, thereby necessitating comparisons with modern species. Here we report the detailed molecular composition and microanatomy of the eyes of 54-million-year-old crane-flies, which together provide a proxy for the interpretation of optical systems in some other ancient arthropods. These well-preserved visual organs comprise calcified corneal lenses that are separated by intervening spaces containing eumelanin pigment. We also show that eumelanin is present in the facet walls of living crane-flies, in which it forms the outermost ommatidial pigment shield in compound eyes incorporating a chitinous cornea. To our knowledge, this is the first record of melanic screening pigments in arthropods, and reveals a fossilization mode in insect eyes that involves a decay-resistant biochrome coupled with early diagenetic mineralization of the ommatidial lenses. The demonstrable secondary calcification of lens cuticle that was initially chitinous has implications for the proposed calcitic corneas of trilobites, which we posit are artefacts of preservation rather than a product of in vivo biomineralization4-7. Although trilobite eyes might have been partly mineralized for mechanical strength, a (more likely) organic composition would have enhanced function via gradient-index optics and increased control of lens shape.

High conductivity Sepia melanin ink films for environmentally benign printed electronics.

Melanins (from the Greek µÎ­λας, mélas, black) are bio-pigments ubiquitous in flora and fauna. Eumelanin is an insoluble brown-black type of melanin, found in vertebrates and invertebrates alike, among which Sepia (cuttlefish) is noteworthy. Sepia melanin is a type of bio-sourced eumelanin that can readily be extracted from the ink sac of cuttlefish. Eumelanin features broadband optical absorption, metal-binding affinity and antioxidative and radical-scavenging properties. It is a prototype of benign material for sustainable organic electronics technologies. Here, we report on an electronic conductivity as high as 10-3 S cm-1 in flexographically printed Sepia melanin films; such values for the conductivity are typical for well-established high-performance organic electronic polymers but quite uncommon for bio-sourced organic materials. Our studies show the potential of bio-sourced materials for emerging electronic technologies with low human- and eco-toxicity.

Metal-Loaded Synthetic Melanin via Oxidative Polymerization of Neurotransmitter Norepinephrine Exhibiting High Photothermal Conversion.

Polydopamine (PDA)-derived melanin-like materials exhibit significant photothermal conversion owing to their broad-spectrum light absorption. However, their low near-infrared (NIR) absorption and inadequate hydrophilicity compromise their utilization of solar energy. Herein, we developed metal-loaded poly(norepinephrine) nanoparticles (PNE NPs) by predoping metal ions (Fe3+, Mn3+, Co2+, Ca2+, Ga3+, and Mg2+) with norepinephrine, a neuron-derived biomimetic molecule, to address the limitations of PDA. The chelation between catechol and metal ions induces a ligand-to-metal charge transfer (LMCT) through the formation of donor-acceptor pairs, modulating the light absorption behavior and reducing the band gap. Under 1 sun illumination, the Fe-loaded PNE coated wood evaporator achieved a high seawater evaporation rate and efficiency of 1.75 kg m-2 h-1 and 92.4%, respectively, owing to the superior hydrophilicity and photothermal performance of PNE. Therefore, this study offers a comprehensive exploration of the role of metal ions in enhancing the photothermal properties of synthetic melanins.

Eumelanin-like Poly(levodopa) Nanoscavengers for Inflammation Disease Therapy.

In the current years, polydopamine nanoparticles (PDA NPs) have been extensively investigated as an eumelanin mimic. However, unlike natural eumelanin, PDA NPs contain no 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-derived units and may be limited in certain intrinsic properties; superior eumelanin-like nanomaterials are still actively being sought. Levodopa (l-DOPA) is a natural eumelanin precursor and expected to convert into DHICA and further remain within the final product through covalent or physical interactions. Herein, poly(levodopa) nanoparticles [P(l-DOPA) NPs] were synthesized with the assistance of zinc oxide as a supplement to synthetic eumelanin. This study found that P(l-DOPA) NPs had ∼90% DHICA-derived subunits on their surface and exhibited superior antioxidant activity compared to PDA NPs due to their looser polymeric microstructure. Benefitting from a stronger ROS scavenging ability, P(l-DOPA) NPs outperformed PDA NPs in treating cellular oxidative stress and acute inflammation. This research opens up new possibilities for the development and application of novel melanin-like materials.

Renewable Electroconductive Hydrogels for Accelerated Diabetic Wound Healing and Motion Monitoring.

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.

Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus.

Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.

Melanin for Photoprotection and Hair Coloration in the Emerging Era of Nanocosmetics.

Nanotechnology is revolutionizing fields of high social and economic impact. such as human health preservation, energy conversion and storage, environmental decontamination, and art restoration. However, the possible global-scale application of nanomaterials is raising increasing concerns, mostly related to the possible toxicity of materials at the nanoscale. The possibility of using nanomaterials in cosmetics, and hence in products aimed to be applied directly to the human body, even just externally, is strongly debated. Preoccupation arises especially from the consideration that nanomaterials are mostly of synthetic origin, and hence are often seen as "artificial" and their effects as unpredictable. Melanin, in this framework, is a unique material since in nature it plays important roles that specific cosmetics are aimed to cover, such as photoprotection and hair and skin coloration. Moreover, melanin is mostly present in nature in the form of nanoparticles, as is clearly observable in the ink of some animals, like cuttlefish. Moreover, artificial melanin nanoparticles share the same high biocompatibility of the natural ones and the same unique chemical and photochemical properties. Melanin is hence a natural nanocosmetic agent, but its actual application in cosmetics is still under development, also because of regulatory issues. Here, we critically discuss the most recent examples of the application of natural and biomimetic melanin to cosmetics and highlight the requirements and future steps that would improve melanin-based cosmetics in the view of future applications in the everyday market.

Catechol-Amyloid Interactions.

This review introduces multifaceted mutual interactions between molecules containing a catechol moiety and aggregation-prone proteins. The complex relationships between these two molecular species have previously been elucidated primarily in a unidirectional manner, as demonstrated in cases involving the development of catechol-based inhibitors for amyloid aggregation and the elucidation of the role of functional amyloid fibers in melanin biosynthesis. This review aims to consolidate scattered clues pertaining to catechol-based amyloid inhibitors, functional amyloid scaffold of melanin biosynthesis, and chemically designed peptide fibers for providing chemical insights into the role of the local three-dimensional orientation of functional groups in manifesting such interactions. These orientations may play crucial, yet undiscovered, roles in various supramolecular structures.

Neuromelanins in brain aging and Parkinson's disease: synthesis, structure, neuroinflammatory, and neurodegenerative role.

Neuromelanins are compounds accumulating in neurons of human and animal brain during aging, with neurons of substantia nigra and locus coeruleus having the highest levels of neuromelanins. These compounds have melanic, lipid, peptide, and inorganic components and are contained inside special autolysosomes. Neuromelanins can participate in neuroprotective or toxic processes occurring in Parkinson's disease according to cellular environment. Their synthesis depends on the concentration of cytosolic catechols and is a protective process since it prevents the toxic accumulation of catechols-derived reactive compounds. Neuromelanins can be neuroprotective also by binding reactive/toxic metals to produce stable and non-toxic complexes. Extraneuronal neuromelanin released by dying dopamine neurons in Parkinson's disease activates microglia which generate reactive oxygen species, reactive nitrogen species, and proinflammatory molecules, thus producing still neuroinflammation and neuronal death. Synthetic neuromelanins have been prepared with melanic, protein structure, and metal content closely mimicking the natural brain pigment, and these models are also able to activate microglia. Neuromelanins have different structure, synthesis, cellular/subcellular distribution, and role than melanins of hair, skin, and other tissues. The main common aspect between brain neuromelanin and peripheral melanin is the presence of eumelanin and/or pheomelanin moieties in their structure.

Melanin biopolymers from microbial world with future perspectives-a review.

Melanin is an amorphous polymer made of heterogeneous functional groups synthesized by diverse organisms including fungi, bacteria, animals, and plants. It was widely acknowledged for its biological processes and its key role in the protection of organisms from environmental stress. Recently, melanin clutches attention in the field of nanobiotechnology, drug delivery, organic semiconductors and bioelectronics, environmental bioremediation, photoprotection, etc., Furthermore, melanin from natural sources like microbial community shows antimicrobial, fighting cancer, radical scavenging, cosmeceuticals, and many therapeutic areas as well. Though the multipotentiality nature of melanin has been put forth, real-world applications still flag fall behind, which might be anticipated to the inadequate and high price essence of natural melanin. However, current bioprocess technologies have paved for the large-scale or industrial production of microbial melanin, which could help in the replacement of synthetic melanin. Thus, this review emphasizes the various sources for melanin, i.e., types-based on its pathways and its chemical structures, functional efficiency, physical properties, and conventional and modern methods of both extraction and characterization. Moreover, an outlook on how it works in the field of medicine, bioremediation, and other related areas provides perspectives on the complete exploitation of melanin in practical applications of medicine and the environment.

Fungi as a source of eumelanin: current understanding and prospects.

Melanins represent a diverse collection of pigments with a variety of structures and functions. One class of melanin, eumelanin, is recognizable to most as the source of the dark black color found in cephalopod ink. Sepia officinalis is the most well-known and sought-after source of non-synthetic eumelanin, but its harvest is limited by the availability of cuttlefish, and its extraction from an animal source brings rise to ethical concerns. In recent years, these limitations have become more pressing as more applications for eumelanin are developed-particularly in medicine and electronics. This surge in interest in the applications of eumelanin has also fueled a rise in the interest of alternative, bio-catalyzed production methods. Many culinarily-utilized fungi are ideal candidates in this production scheme, as examples exist which have been shown to produce eumelanin, their growth at large scales is well understood, and they can be cultivated on recaptured waste streams. However, much of the current research on the fungal production of eumelanin focuses on pathogenic fungi and eumelanin's role in virulence. In this paper, we will review the potential for culinary fungi to produce eumelanin and provide suggestions for new research areas that would be most impactful in the search for improved fungal eumelanin producers.

A Model Eumelanin from 5,6-Dihydroxyindole-2-Carboxybutanamide Combining Remarkable Antioxidant and Photoprotective Properties with a Favourable Solubility Profile for Dermo-Cosmetic Applications.

The search for new synthetic melanin-related pigments that maintain the antioxidant and photoprotective properties of naturally occurring dark eumelanins, while overcoming their unfavorable solubility, and molecular heterogeneity is presently a very active issue for dermo-cosmetic purposes. In this work, we explored the potential of a melanin obtained from the carboxybutanamide of a major eumelanin biosynthetic precursor, 5,6-dihydroxyindole-2-carboxylic acid (DHICA), by aerobic oxidation under slightly alkaline conditions. Analysis of the pigment by EPR, ATR-FTIR and MALDI MS indicated a substantial structural similarity to DHICA melanin, while investigation of the early intermediates confirmed unchanged regiochemistry of the oxidative coupling. The pigment exhibited a UVA-visible absorption even more intense than that of DHICA melanin, and a noticeable solubility in polar solvents of dermo-cosmetic relevance. The hydrogen- and/or electron-donor ability, and the iron (III) reducing power as determined by conventional assays provided evidence for marked antioxidant properties not merely ascribable to the more favorable solubility profile, while the inhibitory action of the radical- or photosensitized solar light-induced lipid peroxidation was more marked compared to that of DHICA melanin. Overall, these results hint at this melanin, which remarkable properties are, in part, due to the electronic effects of the carboxyamide functionality as a promising functional ingredient for dermo-cosmetic formulations.

Characterization and Biological Activities of Melanin from the Medicinal Fungi Ophiocordyceps sinensis.

Melanin is a complex natural pigment that is widely present in fungi. The mushroom Ophiocordyceps sinensis has a variety of pharmacological effects. The active substances of O. sinensis have been extensively studied, but few studies have focused on the O. sinensis melanin. In this study, the production of melanin was increased by adding light or oxidative stress, namely, reactive oxygen species (ROS) or reactive nitrogen species (RNS), during liquid fermentation. Subsequently, the structure of the purified melanin was characterized using elemental analysis, ultraviolet-visible absorption spectrum, Fourier transform infrared (FTIR), electron paramagnetic resonance (EPR), and pyrolysis gas chromatography and mass spectrometry (Py-GCMS). Studies have shown that O. sinensis melanin is composed of C (50.59), H (6.18), O (33.90), N (8.19), and S (1.20), with maximum absorbance at 237 nm and typical melanin structures such as benzene, indole, and pyrrole. Additionally, the various biological activities of O. sinensis melanin have been discovered; it can chelate heavy metals and shows a strong ultraviolet-blocking ability. Moreover, O. sinensis melanin can reduce the levels of intracellular reactive oxygen species and counteract the oxidative damage of H2O2 to cells. These results can help us to develop applications of O. sinensis melanin in radiation resistance, heavy metal pollution remediation, and antioxidant use.

Functionalization of and through Melanin: Strategies and Bio-Applications.

A unique feature of nanoparticles for bio-application is the ease of achieving multi-functionality through covalent and non-covalent functionalization. In this way, multiple therapeutic actions, including chemical, photothermal and photodynamic activity, can be combined with different bio-imaging modalities, such as magnetic resonance, photoacoustic, and fluorescence imaging, in a theragnostic approach. In this context, melanin-related nanomaterials possess unique features since they are intrinsically biocompatible and, due to their optical and electronic properties, are themselves very efficient photothermal agents, efficient antioxidants, and photoacoustic contrast agents. Moreover, these materials present a unique versatility of functionalization, which makes them ideal for the design of multifunctional platforms for nanomedicine integrating new functions such as drug delivery and controlled release, gene therapy, or contrast ability in magnetic resonance and fluorescence imaging. In this review, the most relevant and recent examples of melanin-based multi-functionalized nanosystems are discussed, highlighting the different methods of functionalization and, in particular, distinguishing pre-functionalization and post-functionalization. In the meantime, the properties of melanin coatings employable for the functionalization of a variety of material substrates are also briefly introduced, especially in order to explain the origin of the versatility of melanin functionalization. In the final part, the most relevant critical issues related to melanin functionalization that may arise during the design of multifunctional melanin-like nanoplatforms for nanomedicine and bio-application are listed and discussed.

Chemoenzymatic Isolation and Characterization of High Purity Mammalian Melanin.

Although melanin is one of the most ubiquitous polymers in living systems, our understanding of its molecular structure, biosynthesis and biophysical properties has been limited to only a small number of organisms other than humans. This is in part due to the difficulty associated with isolating pure melanin. While purification methods exist, they typically involve harsh treatments with strong acid/base conditions combined with elevated temperatures that can lead to the polymer backbone degradation. To be successful, a viable isolation method must deliver a selective, yet complete degradation of non-melanin biopolymers as well as remove small molecule metabolites that are not integrative to the melanin backbone. Here, we demonstrate the use of chemoenzymatic processing guided by fluorescent probes for the purification and isolation of native mammalian melanin without significant induction of chemical degradation. This multi-step purification-tracking methodology enables quantitative isolation of pure melanin from mammalian tissue for spectroscopic characterization.

Contrast mechanisms in pump-probe microscopy of melanin.

Pump-probe microscopy of melanin in tumors has been proposed to improve diagnosis of malignant melanoma, based on the hypothesis that aggressive cancers disaggregate melanin structure. However, measured signals of melanin are complex superpositions of multiple nonlinear processes, which makes interpretation challenging. Polarization control during measurement and data fitting are used to decompose signals of melanin into their underlying molecular mechanisms. We then identify the molecular mechanisms that are most susceptible to melanin disaggregation and derive false-coloring schemes to highlight these processes in biological tissue. We demonstrate that false-colored images of a small set of melanoma tumors correlate with clinical concern. More generally, our systematic approach of decomposing pump-probe signals can be applied to a multitude of different samples.

RGD-functionalised melanin nanoparticles for intraoperative photoacoustic imaging-guided breast cancer surgery.

PURPOSE: Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. METHODS: The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. RESULTS: The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. CONCLUSION: These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.

Biomimetic Chiral Photonic Materials with Tunable Metallic Colorations Prepared from Chiral Melanin-like Nanorods for UV Shielding, Humidity Sensing, and Cosmetics.

Many biological species combine the helical organization of cellulose or chitin microfibrils with broadband light absorption of black melanin to produce brilliant structural colors with metallic and glossy effects and other diverse functions. In this work, based on core-shell CNC@PDA chiral nanorods consisting of cellulose nanocrystals (CNCs) as the core and melanin-like polydopamine (PDA) as the shell that can form well-defined chiral liquid crystal phases, we report chiral photonic materials that closely mimic the unique coloration mechanisms and functionalities mastered by several biological species. The photonic films formed by such single CNC@PDA nanorods have brilliant iridescent structural colors originating from selective reflection of circularly polarized lights by the helical organization of CNC@PDAs across the films. Furthermore, the colors of such films have background-independent brightness, high visibility, and metallic effects that arise from the light absorption of the PDA component. Especially, the color ranges and metallic effects of the films can be conveniently tuned by varying the thickness of the PDA shell. In addition, the UV absorption and hygroscopic properties of PDA endow these CNC@PDA films with efficient broadband UV shielding and sensitive humidity-induced dynamic color changes. Due to the mussel-like superior adhesion of PDA, CNC@PDA-based photonic coatings can be formed conformably onto diverse kinds of substrates. A shiny eye shadow with viewing angle-dependent colorful patterns was used to demonstrate the potential applications. With combinations of multiple unique properties in one photonic material fabricated from a single building block, these CNC@PDA-based films are expected to have potential applications in cosmetics, UV protection, anticounterfeiting, chiral reflectors, etc.

Designed Amyloid Fibers with Emergent Melanosomal Functions.

Short peptides designed to self-associate into amyloid fibers with metal ion-binding ability have been used to catalyze various types of chemical reactions. This manuscript demonstrates that one of these short-peptide fibers coordinated with CuII can exhibit melanosomal functions. The coordinated CuII and the amyloid structure itself are differentially functional in accelerating oxidative self-association of dopamine into melanin-like species and in regulating their material properties (e.g., water dispersion, morphology, and the density of unpaired electrons). The results have implications for the role of functional amyloids in melanin biosynthesis and for designing peptide-based supramolecular structures with various emergent functions.