Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation.

OBJECTIVES: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls. METHODOLOGY: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Sídák's multiple comparisons test was used to compare groups. RESULTS: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment. CONCLUSION: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

Computational prediction of analog compounds of the membrane protein MCHR1 antagonists ALB-127158 and KRX-104130.

Obesity, which is already pervasive throughout the world, endangers public health by raising the prevalence of metabolic disorders and making their treatment more difficult. The development of drugs to treat obesity is a focus of effort. Melanin concentrated hormone receptor 1 (MCHR1) is the target of some of these therapeutic possibilities since as increased levels of melanin concentrated hormone have been found in obesity models. Known MCHR1 antagonists include BMS-830216, GW-856464, NGD-4715, ALB-127158, and AMG 076, but many have failed phase-I clinical studies. As a potential treatment for cardiotoxicity, KRX-104130 has only recently been identified. As MCH system is potentially effective target for treatment of obesity, in silico research into interaction between MCHR1 and its antagonists at molecular level was the primary goal of this study. Analogues ALB-127158 and KRX-104130 were screened among the RealEnamine library. The complexes obtained by molecular docking were embedded in mimics brain-cell membrane and simulated for 540 ns, and then MM-GBSA were calculated with MMPBSA.py. With all these computational studies, similar or different aspects of selected analogous compounds to ALB-127158 and KRX-104130 were investigated. The specificity of this study was that it analyzed MCHR1 protein as embedded in membrane. It was concluded that KRX-104130's analogue Z1922310273 and ALB-127158's analogue PV-002757495233 did not cause a difference in terms of phospholipid membrane properties. In addition, all ligands remained stable in putative binding site. It has been suggested that PV-002757495233 and Z1922310273 compounds can be evaluated as MCHR1 antagonists when all these outputs are considered in melting pots.

Herbal Melanin Inhibits Real-Time Cell Proliferation, Downregulates Anti-Apoptotic Proteins and Upregulates Pro-Apoptotic p53 Expression in MDA-MB-231 and HCT-116 Cancer Cell Lines.

Background and Objectives: Cancer is the second-most-important deadly disease in the world, leading to severe socioeconomic consequences and posing a public threat. Consequently, breast and colorectal cancers are significant cancer types that affect women and men more commonly, respectively. Treatment failure or recurrent diseases frequently occur due to resistance, in addition to the side effects of the currently available anticancer agents. Therefore, in this study, herbal melanin anticancer activity was investigated against human breast adenocarcinoma (MDA-MB-231) and human colorectal (HCT 116) cell proliferation and the expression of downregulated anti-apoptotic proteins and upregulated pro-apoptotic p53. Materials and Methods: MDA-MB-231 and HCT 116 cells were monitored for their real-time proliferation properties using Xcelligence. Herbal melanin of various concentrations significantly inhibited MDA-MB-231 and HCT 116 cell proliferation. Then, the expression of proapoptotic and anti-apoptotic proteins such as p53, Bcl-2 and Bcl-xl was studied using Western blotting. Results: The Bcl-2 and Bcl-xl expressions were downregulated, while the p53 expression was upregulated after treatment with herbal melanin. Similarly, the expression of apoptotic proteins such as Bcl-2, Bcl-xl, XIAP, Survivin, Bid, Bax, p53, Cytochrome C, PARP genes and mRNA was studied after herbal melanin treatment using real-time PCR, which revealed the downregulation of Bcl-2, Bcl-xl, XIAP and Survivin and the upregulation of Bid, Bax, p53, Cytochrome C and PARP apoptotic protein expression. Also, caspase 3 and 9 expressions were monitored after the treatment with herbal melanin, which revealed the upregulation of both the MDA-MB-231 and HCT 116 cell types. Conclusions: Overall, herbal melanin can be used as an alternative anticancer agent against the MDA-MB-231 and HCT 116 cell types.

Treatment of melasma with platelet-rich plasma: A self-controlled clinical trial.

Melasma is a common circumscribed hypermelanosis of sun-exposed areas of the skin. Platelet-Rich Plasma therapy has been evidenced to inhibit melanin synthesis in animals and humans. To determine the effectiveness of platelet-rich plasma as a treatment for melasma. Twenty female patient with melasma were involved in this study. The intervention included three Platelet-Rich Plasma application sessions at 15-day intervals. Patients were evaluated before and after treatment. Variables measured included the facial melanin concentration using the melasma area and severity index score, melasma quality of life scale satisfaction grade, and histologic changes. Mean age was 41 ± 7 years. An initial MELASQOL score of 42 ± 14.8 and final score of 16.6 ± 7.2 (p = 0.008) were reported; the initial and final MASI score were 15.5 ± 8.4 and 9.5 ± 7.2 (p = 0.001), respectively. The dermatoscopy examination revealed a decrease in pigmentation after intervention (p = 0.001). Histopathologic improvement was detected in reductions in cutaneous atrophy (14 [70%] vs. 11 [55%]), solar elastosis (15 [75%] vs.11 [55%]), and inflammatory infiltrate (9 [45%] vs. 6 [30%]), before and after treatment, respectively. The intervention was associated with decreased intensity of the melasma patch and improved skin quality, shown by the MELASQOL and MASI scores.

Combination of a 755-nm picosecond laser and hydroquinone 2% cream versus hydroquinone 2% cream alone for the treatment of melasma: A randomized, split-face, and controlled trial.

BACKGROUND: While combined laser and topical treatments are currently a common approach to melasma treatment, data on the efficacy and safety of this combined therapy remain scarce, with studies showing varied results. OBJECTIVE: To compare the efficacy and safety of hydroquinone (HQ) cream alone versus HQ cream combined with 755-nm picosecond (PS) laser in the treatment of melasma. METHOD: Twenty subjects presenting with mixed-type melasma were enrolled in the study. All patients were instructed to apply 2% HQ cream to both sides of the face for 4 weeks. Randomly assigned hemifaces of all patients thereafter received 5 biweekly PS laser treatments. Objective (measurement of average melanin content and melanin index) and subjective (grading of modified melasma area and severity index [mMASI] score and global percentage of pigment clearance) assessments of melasma clearance, and occurrence of adverse effects were evaluated at 1-, 3-, and 6-months after the final laser treatment. RESULTS: mMASI scores were significantly improved from baseline for both sides (p = 0.006 HQ alone, p < 0.001 HQ + PS laser), with no statistically significant difference when comparing HQ alone versus HQ + PS laser. Objective assessments (measurements of average melanin content and melanin index) of melasma clearance corresponded to the clinical evaluation using mMASI score. Mild postinflammatory hyperpigmentation was observed in 15% of the patients on the laser-treated side, while no adverse effects were reported on the HQ monotherapy side. CONCLUSIONS: Adjunctive treatment with a 755-nm PS laser does not provide additional benefit to topical HQ in the treatment of melasma. ClinicalTrail.gov PRS. number: NCT04597203.

A first-in-human study of the novel metabolism-based anti-cancer agent SM-88 in subjects with advanced metastatic cancer.

Purpose SM-88 (D,L-alpha-metyrosine; racemetyrosine) is a novel anti-cancer agent, used with melanin, phenytoin, and sirolimus (SMK Therapy). This pilot first-in-human study characterized the safety, tolerability, and efficacy of SMK Therapy in subjects with advanced metastatic cancer. Methods All subjects (n = 30) received SMK Therapy for an initial 6 week Cycle (5 days on, 2 off per week) and continued if well tolerated. Safety signals, clinical response, overall survival, progression free survival (PFS), and quality of life changes were assessed. Results The most common drug related adverse events were hyperpigmentation and rash. All drug related adverse events were mild to moderate in intensity. Following treatment with SMK Therapy, 4 subjects achieved complete response, 6 partial response, and 17 stable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (total clinical benefit 90%). Responses were observed within 6 weeks, and continued to improve, with 3 complete and 3 partial responders achieving best response after at least 3.2 months. Durable stable disease was observed, lasting a median duration of 11 months (range 1-31 months). Median overall survival for all subjects was 29.8 months, and median PFS was 13 months. Following 6 weeks of treatment, most (83.3%) subjects showed an improvement in Eastern Cooperative Oncology Group (ECOG) score and an improvement in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ 30) global health status (baseline 61.2 ± 25.0; end of Cycle 1 80.7 ± 14.7; n = 29; p < 0.001). Conclusions The results of this study support continued development of SM-88.

Tetrahedral framework nucleic acid loaded with glabridin: A transdermal delivery system applicated to anti-hyperpigmentation.

Topical application of tyrosinase inhibitors, such as hydroquinone and arbutin, is the most common clinical treatment for hyperpigmentation. Glabridin (Gla) is a natural isoflavone that inhibits tyrosinase activity, free radical scavenging, and antioxidation. However, its water solubility is poor, and it cannot pass through the human skin barrier alone. Tetrahedral framework nucleic acid (tFNA), a new type of DNA biomaterial, can penetrate cells and tissues and can be used as carriers to deliver small-molecule drugs, polypeptides, and oligonucleotides. This study aimed to develop a compound drug system using tFNA as the carrier to transport Gla and deliver it through the skin to treat pigmentation. Furthermore, we aimed to explore whether tFNA-Gla can effectively alleviate the hyperpigmentation caused by increased melanin production and determine whether tFNA-Gla exerts substantial synergistic effects during treatment. Our results showed that the developed system successfully treated pigmentation by inhibiting regulatory proteins related to melanin production. Furthermore, our findings showed that the system was effective in treating epidermal and superficial dermal diseases. The tFNA-based transdermal drug delivery system can thus develop into novel, effective options for non-invasive drug delivery through the skin barrier.

Melanogenesis Inhibitory Activity, Chemical Components and Molecular Docking Studies of Prunus cerasoides Buch.-Ham. D. Don. Flowers.

Safe depigmenting agents are currently increasing in the cosmetic or pharmaceutical industry because various compounds have been found to have undesirable side effects. Therefore, the present study aimed to investigate the melanogenesis inhibitory effects of Prunus cerasoides Buch. -Ham. D. Don. flower extracts and their molecular mechanism in B16F10 mouse melanoma cells. Moreover, we also examined phenolic and flavonoid contents, antioxidant activity, chemical constituents of potential extracts, and molecular docking. The highest phenolic and flavonoid contents with the greatest scavenging activity were found in the butanol extract of the P. cerasoides flower compared to other extracts. From all extracts, only crude, diethyl ether, and butanol extracts showed an inhibition of mushroom tyrosinase activity, cellular tyrosinase activity, and melanin content as well as the downregulation of the gene expression of the microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in α-MSH-stimulated B16F10 cells. Based on the molecular docking study, n-hexadecanoic acid, heptadecanoic acid, octadecanoic acid, 9,12-octadecadienoic acid, 9,12,15-octadecanoic acid, and eicosanoic acid might show an inhibitory effect against tyrosinase and MITF. In conclusion, this finding demonstrates that both the diethyl ether and butanol extracts of the P. cerasoides flower can effectively reduce tyrosinase activity and melanin synthesis through the downregulation of the melanogenic gene expression in B16F10 cells and through the molecular docking study. Taken together, the diethyl ether and butanol extracts of the P. cerasoides flower could be an anti-melanogenic ingredient for hyperpigmentary or melasma treatment.

Understanding Melasma-How Can Pharmacology and Cosmetology Procedures and Prevention Help to Achieve Optimal Treatment Results? A Narrative Review.

Melasma is a chronic skin condition that involves the overproduction of melanin in areas exposed to ultraviolet radiation. Melasma treatment is long-term and complicated with recurrence and resistance to treatment. The pathogenesis of melasma is highly complex with multiple pathologies occurring outside of the skin pigment cells. It includes photoaging, excessive melanogenesis, an increased number of mast cells, increased vascularization, and basement membrane damage. In addition, skin lesions related to melasma and their surrounding skin have nearly 300 genes differentially expressed from healthy skin. Traditionally, melasma was treated with topical agents, including hydroquinone, tretinoin, glucocorticosteroids and various formulations; however, the current approach includes the topical application of a variety of substances, chemical peels, laser and light treatments, mesotherapy, microneedling and/or the use of systemic therapy. The treatment plan for patients with melasma begins with the elimination of risk factors, strict protection against ultraviolet radiation, and the topical use of lightening agents. Hyperpigmentation treatment alone can be ineffective unless combined with regenerative methods and photoprotection. In this review, we show that in-depth knowledge associated with proper communication and the establishment of a relationship with the patient help to achieve good adherence and compliance in this long-term, time-consuming and difficult procedure.

Functionalized chitosan nanoparticles for cutaneous delivery of a skin whitening agent: an approach to clinically augment the therapeutic efficacy for melasma treatment.

The increase in the production of melanin level inside the skin prompts a patient-inconvenient skin color disorder namely; melasma. This arouses the need to develop efficacious treatment modalities, among which are topical nano-delivery systems. This study aimed to formulate functionalized chitosan nanoparticles (CSNPs) in gel form for enhanced topical delivery of alpha-arbutin as a skin whitening agent to treat melasma. Ionic gelation method was employed to prepare α-arbutin-CSNPs utilizing a 24 full factorial design followed by In vitro, Ex vivo and clinical evaluation of the nano-dispersions and their gel forms. Results revealed that the obtained CSNPs were in the nanometer range with positive zeta potential, high entrapment efficiency, good stability characteristics and exhibited sustained release of α-arbutin over 24 h. Ex vivo deposition of CSNPs proved their superiority in accumulating the drug in deep skin layers with no transdermal delivery. DSC and FTIR studies revealed the successful amorphization of α-arbutin into the nanoparticulate system with no interaction between the drug and the carrier system. The comparative split-face clinical study revealed that α-arbutin loaded CSNPs hydrogels showed better therapeutic efficacy compared to the free drug hydrogel in melasma patients, as displayed by the decrease in: modified melasma area and severity index (mMASI) scores, epidermal melanin particle size surface area (MPSA) and the number of epidermal monoclonal mouse anti-melanoma antigen recognized by T cells-1 (MART-1) positive cells which proved that the aforementioned system is a promising modality for melasma treatment.

The formulation and efficacy of topical Dorema ammoniacum in treating Melasma: a randomized double-blind, placebo-controlled trial.

OBJECTIVES: An acquired melanin-related hyperpigmentation that occurs in sun exposure areas is Melasma which presents as gray-brown ridges and macules with prominent margins on the skin. The aim of this assay was to assess the formulation and efficacy of topical Dorema ammoniacum among Melasma patients. METHODS: This study was a 30 days double-blind, randomized clinical trial in Melasma with a placebo group. The study was carried out on 49 patients with Melasma attending Haji Daii Nursing Center in Kermanshah, Iran. Optimized topical formulation of D. ammoniacum gum extract was prepared by evaluating the characteristics of different topical formulations of this plant. Mean Melasma severity index (MMASI) instrument was applied to assess the product effectiveness and to determine the skin stains. Patients were pursued to receive the treatment throughout the 30 days trial. This scaling was accomplished before the intervention and 30 days after the use of the herbal product. To analyze the quantitative variables, t-test and Mann-Whitney test were evaluated by SPSS 21 software, and p-value <0.05 was considered as the statistically significant. RESULTS: The survey was performed on 40 female subjects (81.6%) and nine male subjects (18.4%) with the mean age of 32.18 ± 8.69. According to the results, the mean MSI in the drug group was significantly lower than before treatment and decreased from 86.98 ± 69.48 to 31.03 ± 32.62 (p-value <0.05). CONCLUSIONS: In compliance with findings this survey revealed a positive effect of the cream formulation of D. ammoniacum extract on Melasma. As it was represented no side effects, this formulation is appropriate for the treatment of Melasma.

Anti-infective properties of the melanin-glucan complex obtained from medicinal tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr. (Aphyllophoromycetideae).

The goal of this investigation was to comparatively study the efficiency of traditionally used anti-infective drugs and biopolymer complexes originated from the medicinal mushroom Fomes fomentarius (L.:Fr.) Fr.: 1) water-soluble melanin-glucan complex (MGC; -80% melanins and -20% beta-glucans) and 2) insoluble chitin-glucan-melanin complex (ChGMC; -70% chitin, -20% beta-glucans, and -10% melanins). Infectious materials (Helicobacter pylori, Candida albicans, and Herpes vulgaris I and HIV-1(zmb) were used in pure cultures of in vitro and in vivo models on experimental animals. Comparison studies of fungal biopolymers and effective modern antifungal, antibacterial, and antiviral drugs were used in in vitro models. The comparative clinical efficiency of ChGMC and of etiotropic pharmaceuticals in models of H. pylori, C. albicans, and H. vulgaris I infection contamination were studied. Using in vitro models, it was established that MGC completely depresses growth of C. albicans. MGC had an antimicrobial effect on H. pylori identical to erythromycin in all concentrations, and had a stronger action on this bacterium than other tested antibiotics. Tested MGC possesses simultaneously weak toxicity and high anti-HIV-1 activity in comparison with zidovudine (Retrovir). The obtained results show that CLUDDT therapy in Wistar rats with the application of ChGMC is, on average, 1.35-1.43 times as effective as a traditional one. Considering the absence of MGC and ChGMC toxic properties on blood cells even in very high concentrations, these complexes may be used as a source of biopolymers for the creation of essentially new agents for wide application in infectious pathology.

A triple-stimulus responsive melanin-based nanoplatform with an aggregation-induced emission-active photosensitiser for imaging-guided targeted synergistic phototherapy/hypoxia-activated chemotherapy.

Multimodal synergistic therapy has gained increasing attention in cancer treatment to overcome the limitations of monotherapy and achieve high anticancer efficacy. In this study, a synergistic phototherapy and hypoxia-activated chemotherapy nanoplatform based on natural melanin nanoparticles (MPs) loaded with the bioreduction prodrug tirapazamine (TPZ) and decorated with hyaluronic acid (HA) was developed. A self-reporting aggregation-induced emission (AIE)-active photosensitizer (PS) (BATTMN) was linked to the prepared nanoparticles by boronate ester bonds. The MPs and BATTMN-HA played roles as quenchers for PS and cancer targeting/photodynamic moieties, respectively. As a pH sensitive bond, the borate ester bonds between HA and BATTMN are hydrolysed in the acidic cancer environment, thereby separating BATTMN from the nanoparticles and leading to the induction of fluorescence for imaging-guided synergistic phototherapy/hypoxia-activated chemotherapy under dual irradiation. TPZ can be released upon activation by pH, near-infrared (NIR) and hyaluronidase (Hyal). Particularly, the hypoxia-dependent cytotoxicity of TPZ was amplified by oxygen consumption in the tumor intracellular environment induced by the AIE-active PS in photodynamic therapy (PDT). The nanoparticles developed in our research showed favorable photothermal conversion efficiency (η = 37%), desired cytocompatibility, and excellent synergistic therapeutic efficacy. The proposed nanoplatform not only extends the application scope of melanin materials with AIE-active PSs, but also offers useful insights into developing multistimulus as well as multimodal synergistic tumor treatment.

Photothermal therapy-induced immunogenic cell death based on natural melanin nanoparticles against breast cancer.

A photothermal and immune co-therapy strategy based on natural melanin nanoparticles was developed for treating primary and abscopal breast cancers.

Nondestructive Evaluations of Melanin-related Compounds in the Skin Using Electron Paramagnetic Resonance and Permeability Measurements.

Melanin-related compounds in paraffin-embedded tissue specimens of basal cell carcinoma (BCC), seborrheic keratosis (SK), malignant melanoma (MM), and nevus pigmentosus (NP) were nondestructively investigated using permeability measurements (light penetration into pigmented lesion), X-band (9.4 GHz) electron paramagnetic resonance (EPR), and EPR imaging (EPRI). The paramagnetic species in BCC, SK, MM, and NP specimens were analyzed using intensity, linewidth, spectral pattern, and X-band EPRI. The EPR spectra of BCC, SK, and NP showed a single line pattern. The EPR signal intensities of the BCC, SK, and NP samples corresponded to the permeability values that are directly related to pigment color tone, except for MM. The correlation coefficient between EPR and permeability was supported by the high degree of linear relation in the range. We further analyzed MM and speculated that MM contains an additional signal of the pheomelanin radical. In MM and NP samples, two-dimensional (2D) EPRI revealed paramagnetic species distribution and different magnitudes. The paramagnetic (radical) species are directly related to the pigmented lesion site. To conclude, spectroscopic analyses suggest that pheomelanin-related compounds may exist in malignant melanoma.

The Role of Melanin to Dissociate Oxygen from Water to Treat Retinopathy of Prematurity.

BACKGROUND: Retinopathy of Prematurity (ROP) is a potentially blinding disorder that commonly afflicts premature infants who are born prior to 31weeks of gestation or with a body weight less than 1250 grams (about 2.75 pounds). Another risk factor is excessive oxygen in incubators, which can lead to blindness. A compounding factor is that survival rates for premature infants are rising with concomitantly more cases of ROP. We have reported an unsuspected intrinsic property of melanin to dissociate water. This capability can be considered an alternative treatment option for adult and neonatal diseases. It is known that exogenous surfactant administration suppresses bronchopulmonary dysplasia and consequent death, randomized, controlled trials with various respiratory interventions did not show any significant reductions in morbidity and mortality rates. During a descriptive study about the three leading causes of blindness in the world, the ability of melanin to transform light energy into chemical energy through the dissociation of water molecule was unraveled. Initially, during 2 or 3 years; we tried to link together our findings with the widely accepted metabolic pathways already described in molecular pathway databases, which have been developed to collect and organize the current knowledge on metabolism scattered across a multitude of scientific evidence. OBSERVATIONS: The current report demonstrates the main problems that afflict premature babies with an emphasis on the growth of abnormal vessels in the retina, the explanation for which is unknown until date. We also reported a case of a baby who suffered digestive and respiratory problems with a brain haemorrhage that was successfully treated by laser photocoagulation. We hypothesise that most likely this effect was due to the melanin level and melanin itself produces oxygen via dissociating with water molecules. CONCLUSION: We postulate that the intrinsic effect of melanin may easily convert visible and invisible light into chemical energy via a water dissociation reaction similar to the one in plant's chlorophyll, and markedly elevated with diagnosis and treatment of the complications related to premature babies.

In situ growth of Au nanoparticles on natural melanin as biocompatible and multifunctional nanoagent for efficient tumor theranostics.

Natural melanin has been demonstrated to be a biocompatible and efficient nanoagent for the photothermal ablation of tumors, but their practical applications are limited due to their lack of typical imaging functions (CT, MRI, etc.). Thus, to achieve multifunctional melanin-based nanoagents for imaging-guided therapy, for the first time, herein, we report the in situ growth of Au nanoparticles on natural melanin as a model through a simple and safe method. The as-synthesized samples are composed of melanin nanoparticles (diameter: ∼120 nm) whose surface are decorated by small Au nanoparticles with an adjustable size ranging from ∼10 to ∼40 nm. These Au-decorated melanin (Au-M) nanocomposites exhibit satisfactory near infrared (NIR) photoabsorption and high photothermal conversion efficiency of 42.3%. Furthermore, the Au-M nanocomposites have a high X-ray attenuation coefficient and exhibit excellent biocompatibility. When the Au-M solutions were injected into the tumor of a mouse, the tumor could be detected by X-ray computed tomography (CT), photoacoustic (PA) and thermal imaging, and then be thermally ablated under the illumination of an 808 nm laser. Therefore, these Au-M nanocomposites have great potential as a novel multifunctional and biocompatible nanoagent for imaging-guided photothermal tumor ablation.

Erythrocyte-cancer hybrid membrane-camouflaged melanin nanoparticles for enhancing photothermal therapy efficacy in tumors.

Cell membrane coating has emerged as an intriguing biomimetic strategy to endow nanomaterials with functions and properties inherent to source cells for various biomedical applications. Hybrid membrane of different types of cells could be coated onto nanoparticle surface to achieve additional functions. Herein, we fused red blood cell (RBC) membrane together with MCF-7 cell membrane and fabricated an erythrocyte-cancer (RBC-M) hybrid membrane-camouflaged melanin nanoparticle (Melanin@RBC-M) platform for enhancing therapeutic efficacy of photothermal therapy (PTT). The fused RBC-M hybrid membrane vesicles retained both RBC and MCF-7 cell membrane proteins and the resultant Melanin@RBC-M exhibited prolonged blood circulation and homotypic targeting to source MCF-7 cells simultaneously. Interestingly, increasing MCF-7 membrane components in RBC-M significantly enhanced the homotypic targeting function of Melanin@RBC-M while increasing RBC membrane components in RBC-M effectively reduced the cellular uptake of Melanin@RBC-M by macrophages and improved their circulation time in the blood. After intravenous injection into MCF-7 tumor-bearing athymic nude mice, Melanin@RBC-M with 1:1 membrane protein weight ratio of RBC to MCF-7 exhibited significantly higher tumor accumulation and better PTT efficacy compared with other Melanin@RBC-M with different membrane protein weight ratios as well as pristine melanin nanoparticles, due to the optimal balance between prolonged blood circulation and homotypic targeting. In addition, in vitro photoacoustic results revealed that Melanin@RBC-M had a photoacoustic signal enhancement with the increase of nanoparticle size (64 → 148 nm) and the photoacoustic amplitudes increased linearly with nanoparticle concentration at the excitation wavelength ranged from 680 nm to 800 nm, which could be used for quantification of Melanin@RBC-M in vivo. Looking forward, coating hybrid membrane onto nanoparticles could add flexibility and controllability in enhancing nanoparticles functionality and offer new opportunities for biomedical applications.

Neuromelanin can protect against iron-mediated oxidative damage in system modeling iron overload of brain aging and Parkinson's disease.

In Parkinson's disease (PD), dopamine neurons containing neuromelanin selectively degenerate. Neuromelanin binds iron and accumulates in aging. Iron accumulates in reactive form during aging, PD, and is involved in neurodegeneration. It is not clear how the interaction of neuromelanin and iron can be protective or toxic by modulating redox processes. Here, we investigated the interaction of neuromelanin from human substantia nigra with iron in the presence of ascorbic acid, dopamine, and hydrogen peroxide. We observed that neuromelanin blocks hydroxyl radical production by Fenton's reaction, in a dose-dependent manner. Neuromelanin also inhibited the iron-mediated oxidation of ascorbic acid, thus sparing this major antioxidant molecule in brain. The protective effect of neuromelanin on ascorbate oxidation occurs even in conditions of iron overload into neuromelanin. The blockade of iron into a stable iron-neuromelanin complex prevents dopamine oxidation, inhibiting the formation of neurotoxic dopamine quinones. The above processes occur intraneuronally in aging and PD, thus showing that neuromelanin is neuroprotective. The iron-neuromelanin complex is completely decomposed by hydrogen peroxide and its degradation rate increases with the amount of iron bound to neuromelanin. This occurs in PD when extraneuronal iron-neuromelanin is phagocytosed by microglia and iron-neuromelanin degradation releases reactive/toxic iron.

Peptide-targeted radionuclide therapy for melanoma.

Melanocortin-1 receptor (MC1-R) and melanin are two attractive melanoma-specific targets for peptide-targeted radionuclide therapy for melanoma. Radiolabeled peptides targeting MC1-R/melanin can selectively and specifically target cytotoxic radiation generated from therapeutic radionuclides to melanoma cells for cell killing, while sparing the normal tissues and organs. This review highlights the recent advances of peptide-targeted radionuclide therapy of melanoma targeting MC1-R and melanin. The promising therapeutic efficacies of 188Re-(Arg(11))CCMSH (188Re-[Cys(3,4,10), D-Phe(7),Arg(11)]-alpha-MSH(3-13)), 177Lu- and 212Pb-labeled DOTA-Re(Arg(11))CCMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-[ReO-(Cys(3,4,10), D-Phe(7), Arg(11))]-alpha-MSH(3-13)) and 188Re-HYNIC-4B4 (188Re-hydrazinonicotinamide-Tyr-Glu-Arg-Lys-Phe-Trp-His-Gly-Arg-His) in preclinical melanoma-bearing models demonstrate an optimistic outlook for peptide-targeted radionuclide therapy for melanoma. Peptide-targeted radionuclide therapy for melanoma will likely contribute in an adjuvant setting, once the primary tumor has been surgically removed, to treat metastatic deposits and for treatment of end-stage disease. The lack of effective treatments for metastatic melanoma and end-stage disease underscores the necessity to develop and implement new treatment strategies, such as peptide-targeted radionuclide therapy.