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In this work, we investigate the relationship between the complex hierarchical assembly structure of eumelanin, its characteristic broad absorption band, and the highly unusual nonlinear dynamics revealed by pump-probe or transient absorption microscopy. Melanin-like nanoparticles (MelNPs), generated by spontaneous oxidation of dopamine, were created with uniform but adjustable size distributions, and kinetically controlled oxidation was probed with a wide range of characterization methods. This lets us explore the broad absorption bands of eumelanin models at different assembly levels, such as small subunit fractions (single monomeric and oligomeric units and small oligomer stacks), stacked oligomer fractions (protomolecules), and large-scale aggregates of protomolecules (parental particles). Both the absorption and pump-probe dynamics are very sensitive to these structural differences or to the size of intact particles (a surprising result for an organic polymer). We show that the geometric packing order of protomolecules in long-range aggregation is key secondary interactions to extend the absorption band of eumelanin to the low energy spectrum and produce drastic changes in the transient absorption spectrum.

More people die from melanoma after a stage I diagnosis than after a stage IV diagnosis, because the tools available to clinicians do not readily identify which early-stage cancers will be aggressive. Near-infrared pump-probe microscopy detects fundamental differences in melanin structure between benign human moles and melanoma and also correlates with metastatic potential. However, the biological mechanisms of these changes have been difficult to quantify, as many different mechanisms can contribute to the pump-probe signal. We use model systems (sepia, squid, and synthetic eumelanin), cellular uptake studies, and a range of pump and probe wavelengths to demonstrate that the clinically observed effects come from alterations of the aggregated mode from “thick oligomer stacks” to “thin oligomer stacks” (due to changes in monomer composition) and (predominantly) deaggregation of the assembled melanin structure. This provides the opportunity to use pump-probe microscopy for the detection and study of melanin-associated diseases.

Pheomelanin-type nanoparticles (PMNPs) were synthesized through a simple oxidative polymerization of 3,4-dihydroxyphenylalanine (DOPA) in the presence of cysteine by KMnO4. The synthesized PMNPs had a diameter of approximately 100nm, exhibited high dispersion stability in neutral water and various culture media and possessed similar morphology to naturally occurring pheomelanins. The efficiency of photoinduced generation of hydroxyl radicals from PMNPs was determined and related in vitro cell experiments that were carried out, with data being compared to those from eumelanin-type nanoparticles (EMNPs) and natural sepia melanin nanoparticles. Endocytosed PMNPs showed the highest phototoxicity (~50% viability) to UV-irradiated HeLa cells, confirming the direct relationship between phototoxic efficiency and the generation of hydroxyl radicals through the complex processes of the O2 sensitization.

Spherical-shape melanin nanoparticles with good water-dispersibility were successfully synthesized by a simple oxidation polymerization of 3,4-dihydroxy-phenylalanin (DOPA) with . Similar features to those known from natural and synthetic melanin polymers were observed from prepared melanin nanoparticles by FT-IR, UV-Vis., and ESR spectroscopic methods. Their binding ability with several heavy metal ions from aqueous solution was quantitatively investigated, and the maximum binding capacities with melanin nanoparticles to lead, copper, and cadmium ions were obtained as 2.45, 2.17 and 1.88 mmol/g, respectively, which are much larger values than those reported from natural and synthetic melanin polymers. The large binding capacity and fast binding rate of melanin nanoparticles to metal ions can make them an excellent candidate for the remediation of contaminated water.

The contradictory biological function of eumelanin (photoprotection vs photosensitization) has long been a topic of debate in a wide range of disciplines such as chemistry, physics and biology. For understanding full spectrum of eumelanin's photobiological aspect, revealing how eumelanin's complex structural organization dictates its photophysical properties is critical step. Here, we report a practical approach to controlling the hierarchically assembled structure of natural eumelanin, which leads to disassembly of its structure into subunits and oxidized subunits, respectively. Based on the well-characterized model system, it was possible to systematically determine how the photophysical properties of eumelanin are ruled by its hierarchical assembly organization. Particularly, our experiments reveal that the chemical oxidation of eumelanin's subunits, which leads to delamination of their stacked layer structure, is critical to significantly increase their photochemical reactivity to generate ROS under UV irradiation. This result provides clear experimental evidence that oxidative degradation of eumelanin, which might be induced by phagosomal enzymatic activity in the process of melanomagenesis, is responsible for triggering the negative photobiological role of eumelanin such as ROS source needed for development of malignant melanoma.

We present a new melanin-like nanoparticle (MelNP) and its performance evaluation results. This particle is proposed as an exogenous contrast agent for photoacoustic (PA) imaging. Conventional PA contrast agents are based on non-biological materials. In contrast, the MelNPs are organic nanoparticles inspired by natural melanin. Melanin is an endogenous chromophore that has the ability to produce a PA signal in vivo. The developed MelNPs are capable of aggregating with one another under mildly acidic conditions after introducing hydrolysis-susceptible citraconic amide on the surface of bare MelNPs. We ascertained that the physical aggregation of the MelNPs resulted in an increased PA signal strength in the near-infrared window of biological tissue (i.e., 700 nm) without absorption tuning. This phenomenon is likely because of the overlapping thermal fields of the developed MelNPs. The PA signal produced from the developed MelNPs, after exposure to mildly acidic conditions (i.e., pH 6), is 8.1 times stronger than under neutral conditions. This unique characteristic found in this study can be utilized in a practical strategy for highly sensitive in vivo cancer target imaging in response to its acidic microenvironment. This approach to amplify the PA response of MelNPs in clusters could accelerate the use of MelNPs as an alternative to non-biological nanoprobes, so that MelNPs may be applicable in PA imaging and functional PA imaging such as stimuli sensitive, multimodal, and theranostic imaging.

Nonlinear pump-probe microscopy differentiates cutaneous, vulvar and conjunctival melanomas from less dangerous lesions, and can be used to assess metastatic potential. Applications in vivo (knockout mouse models) and in human biopsy are presented.

Melanin-like nanoparticles were synthesized with size control through neutralization of dopamine hydrochloride with NaOH, followed by spontaneous air oxidation of dopamine. Although the particle characteristic of natural melanins was understood to be significantly affected by the biological and structural environment, melanin-lke nanoparticles can be realized through the chemical reactions only. Melanin-like nanoparticles that are

We have developed a simple, efficient, and highly reproducible method to fabricate the large-area biomimetic superhydrophobic polymer surfaces having hierarchical structures of micrometer-sized irregular steps and nanometer-sized fibrils. Commercial Al plates (99.0%) were etched using Beck's dislocation etchant (mixture of HCl and HF) for different time periods in order to alter the structure of the etched Al surfaces from micrometer-sized to highly rough nanometer-sized irregular steps. These hierarchical structures could be easily replicated onto the surface of various thermoplastic polymer plates from the etched Al templates by applying heat and pressure; many polymer replicas without any significant deviations from each other could be duplicated from the same etched Al master templates. All of thermoplastic polymer replicas having hierarchical structures exhibited superhydrophobic properties with water contact angles of larger than 150 degrees. Especially, the surfaces of the high-density polyethylene (HDPE) replicas having nanometer-sized curled strands exhibited superhydrophobicity with a static water contact angle of approximately 160 degrees and a sliding angle of less than 2 degrees. These superhydrophobic HDPE replicas having nanometer-sized curled strands showed excellent stability after being exposed to various organic solvents and aqueous solutions of various pH.

The development of nontoxic and biocompatible imaging agents will create new opportunities for potential applications in clinical MRI diagnosis. Synthetic melanin-like nanoparticles (MelNPs), analogous to natural sepia melanin (a major component of the cuttlefish ink), can be used as contrast agent for MRI. MelNPs complexed with paramagnetic Fe(3+) ions show much higher relaxivity values than existing MRI T1 contrast agents based on gadolinium (Gd) or manganese (Mn); MelNP values at 3T were r1 = 17 and r2 = 18 mM(-1) s(-1) (r2/r1 value of 1.1). With significant enhancement to MRI contrast, this biomimetic approach using MelNPs functionalized with paramagnetic Fe(3+) ions and surface-modified with biocompatible poly(ethylene glycol) units, could provide new insight into how melanin-based bioresponsive and therapeutic imaging probes integrate with their various biological functions.