Tag Archives: melanin

Biosynthetic melanin nanoparticles enabled by genetically engineered bacterium

A January 13, 2023 news item on phys.org announces research into genetically engineering bacteria so they produce melanin nanoparticles, i.e., biosynthetic melanin nanoparticles, Note: Links have been removed,

Photothermal therapy (PTT) has attracted considerable attention for the treatment of tumors because it is minimally invasive and has spatiotemporal selectivity.

Melanin is a kind of multifunctional pigment found widely in mammals, plants and microbes, with great prospects as a PTT agent for cancer treatment. Unfortunately, commercially available melanin is mainly obtained by chemical synthesis or extraction from sepia, which hinders its large-scale production and causes some potential safety hazards.

Recently, a research team led by Prof. Yan Fei from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, together with Prof. Lin Jing from Shenzhen University and Prof. Xu Xiaohong from Guangdong Medical University, heterologously expressed a tyrosinase gene in Escherichia coli to synthesize melanin nanoparticles under mild and environmentally friendly conditions.

Caption: Schematic illustration of biosynthetic melanin nanoparticles for photoacoustic imaging-guided photothermal therapy. Credit: SIAT [Shenzhen Institute of Advanced Technology]

A January 13, 2023 Chinese Academy of Sciences press release (also on EurekAlert but published January 12, 2023), which originated the news item, provides a little more detail about the research,

The biosynthetic melanin nanoparticles exhibited excellent biocompatibility, good stability, and negligible toxicity. “They had strong absorption in the near-infrared region and higher photothermal conversion efficiency (48.9%) than chemically synthesized melanin-like polydopamine nanoparticles under an 808-nm laser irradiation,” said Prof. YAN.

The researchers further evaluated the photoacoustic imaging performance and antitumor efficacy of biosynthetic melanin nanoparticles. The results showed that the biosynthetic melanin nanoparticles had excellent photoacoustic imaging performance and could be used for photoacoustic imaging-guided photothermal therapy in vivo

“Our study provided an alternative approach to synthesize PTT agents with broad application potential in the diagnosis and treatment of cancer,” said Prof. YAN.

Here’s a link to and a citation for the paper,

Biosynthesis of Melanin Nanoparticles for Photoacoustic Imaging Guided Photothermal Therapy by Meijun Fu, Yuping Yang, Zhaomeng Zhang, Yaling He, Yuanyuan Wang, Chenxing Liu, Xiaohong Xu, Jing Lin, Fei Yan. Small DOI: https://doi.org/10.1002/smll.202205343 First published: 29 December 2022

This paper is behind a paywall.

Cyborgs based on melanin circuits

Pigments for biocompatible electronics? According to a March 26, 2019 news item on Nanowerk this is a distinct possibility (Note: A link has been removed),

The dark brown melanin pigment, eumelanin, colors hair and eyes, and protects our skin from sun damage. It has also long been known to conduct electricity, but too little for any useful application – until now.

In a landmark study published in Frontiers in Chemistry (“Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum”), Italian researchers subtly modified the structure of eumelanin by heating it in a vacuum.

“Our process produced a billion-fold increase in the electrical conductivity of eumelanin,” say study senior authors Dr. Alessandro Pezzella of University of Naples Federico II and Dr. Paolo Tassini of Italian National Agency for New Technologies, Energy and Sustainable Economic Development. “This makes possible the long-anticipated design of melanin-based electronics, which can be used for implanted devices due to the pigment’s biocompatibility.”

This is a rather dreamy image to illustrate the point,

Despite extensive research on the structure of melanin, nobody has yet managed to harness its potential in implantable electronics. Image: Shutterstock. [downloaded from https://blog.frontiersin.org/2019/03/26/will-cyborgs-circuits-be-made-from-melanin/]

A March 26, 2019 Frontiers in Chemistry (journal) press release (also on EurekAlert), which originated the news item, expands on the theme,

A young Pezzella had not even begun school when scientists first discovered that a type of melanin can conduct electricity. Excitement quickly rose around the discovery because eumelanin – the dark brown pigment found in hair, skin and eyes – is fully biocompatible.

“Melanins occur naturally in virtually all forms of life. They are non-toxic and do not elicit an immune reaction,” explains Pezzella. “Out in the environment, they are also completely biodegradable.”

Decades later, and despite extensive research on the structure of melanin, nobody has managed to harness its potential in implantable electronics.

“To date, conductivity of synthetic as well as natural eumelanin has been far too low for valuable applications,” he adds.

Some researchers tried to increase the conductivity of eumelanin by combining it with metals, or super-heating it into a graphene-like material – but what they were left with was not truly the biocompatible conducting material promised.

Determined to find the real deal, the Neapolitan group considered the structure of eumelanin.

“All of the chemical and physical analyses of eumelanin paint the same picture – of electron-sharing molecular sheets, stacked messily together. The answer seemed obvious: neaten the stacks and align the sheets, so they can all share electrons – then the electricity will flow.”

This process, called annealing, is used already to increase electrical conductivity and other properties in materials such as metals.

For the first time, the researchers put films of synthetic eumelanin through an annealing process under high vacuum to neaten them up – a little like hair straightening, but with only the pigment.

“We heated these eumelanin films – no thicker than a bacterium – under vacuum conditions, from 30 min up to 6 hours,” describes Tassini. “We call the resulting material High Vacuum Annealed Eumelanin, HVAE.”

The annealing worked wonders for eumelanin: the films slimmed down by more than half, and picked up quite a tan.

“The HVAE films were now dark brown and about as thick as a virus,” Tassini reports.

Crucially, the films had not simply been burnt to a crisp.

“All our various analyses agree that these changes reflect reorganization of eumelanin molecules from a random orientation to a uniform, electron-sharing stack. The annealing temperatures were too low to break up the eumelanin, and we detected no combustion to elemental carbon.”

Having achieved the intended structural changes to eumelanin, the researchers proved their hypothesis in spectacular fashion.

“The conductivity of the films increased billion-fold to an unprecedented value of over 300 S/cm, after annealing at 600°C for 2 hours,” Pezzella confirms.

Although well short of most metal conductors – copper has a conductivity of around 6 x 107 S/cm – this finding launches eumelanin well into a useful range for bioelectronics.

What’s more, the conductivity of HVAE was tunable according to the annealing conditions.

“The conductivity of the films increased with increasing temperature, from 1000-fold at 200°C. This opens the possibility of tailoring eumelanin for a wide range of applications in organic electronics and bioelectronics. It also strongly supports the conclusion from structural analysis that annealing reorganized the films, rather than burning them.”

There is one potential dampener: immersion of the films in water results in a marked decrease in conductivity.

“This contrasts with untreated eumelanin which, albeit in a much lower range, becomes more conductive with hydration (humidity) because it conducts electricity via ions as well as electrons. Further research is needed to fully understand the ionic vs. electronic contributions in eumelanin conductivity, which could be key to how eumelanin is used practically in implantable electronics.” concludes Pezzella.

Here’s a link to and a citation for the paper,

Evidence of Unprecedented High Electronic Conductivity in Mammalian Pigment Based Eumelanin Thin Films After Thermal Annealing in Vacuum by Ludovico Migliaccio, Paola Manini, Davide Altamura, Cinzia Giannini, Paolo Tassini, Maria Grazia Maglione, Carla Minarini, and Alessandro Pezzella. Front. Chem., 26 March 2019 DOI: https://doi.org/10.3389/fchem.2019.00162

This paper is open access.

The ultimate natural sunscreen

For those of us in the northern hemisphere, sunscreen season is on the horizon. While the “ultimate natural sunscreen” researchers from the University of California at San Diego (UCSD) have developed is a long way from the marketplace, this is encouraging news (from a May 17, 2017 news item on Nanowerk),

Chemists, materials scientists and nanoengineers at UC San Diego have created what may be the ultimate natural sunscreen.

In a paper published in the American Chemical Society journal ACS Central Science, they report the development of nanoparticles that mimic the behavior of natural melanosomes, melanin-producing cell structures that protect our skin, eyes and other tissues from the harmful effects of ultraviolet radiation.

“Basically, we succeeded in making a synthetic version of the nanoparticles that our skin uses to produce and store melanin and demonstrated in experiments in skin cells that they mimic the behavior of natural melanosomes,” said Nathan Gianneschi, a professor of chemistry and biochemistry, materials science and engineering and nanoengineering at UC San Diego, who headed the team of researchers. The achievement has practical applications.

A May 17, 2017 UCSD news release, which originated the news item, delves into the research,

“Defects in melanin production in humans can cause diseases such as vitiligo and albinism that lack effective treatments,” Gianneschi added.

Vitiligo develops when the immune system wrongly attempts to clear normal melanocytes from the skin, effectively stopping the production of melanocytes. Albinism is due to genetic defects that lead to either the absence or a chemical defect in tyrosinase, a copper-containing enzyme involved in the production of melanin. Both of these diseases lack effective treatments and result in a significant risk of skin cancer for patients.

“The widespread prevalence of these melanin-related diseases and an increasing interest in the performance of various polymeric materials related to melanin prompted us to look for novel synthetic routes for preparing melanin-like materials,” Gianneschi said.

UC San Diego Ultimate natural sunscreenThe scientists found that the synthetic nanoparticles were taken up in tissue culture by keratinocytes, the predominant cell type found in the epidermis, the outer layer of skin. Photo by Yuran Huang and Ying Jones/UC San Diego

Melanin particles are produced naturally in many different sizes and shapes by animals—for iridescent feathers in birds or the pigmented eyes and skin of some reptiles. But scientists have discovered that extracting melanins from natural sources is a difficult and potentially more complex process than producing them synthetically.

Gianneschi and his team discovered two years ago that synthetic melanin-like nanoparticles could be developed in a precisely controllable manner to mimic the performance of natural melanins used in bird feathers.

“We hypothesized that synthetic melanin-like nanoparticles would mimic naturally occurring melanosomes and be taken up by keratinocytes, the predominant cell type found in the epidermis, the outer layer of skin,” said Gianneschi.

In healthy humans, melanin is delivered to keratinocytes in the skin after being excreted as melanosomes from melanocytes.

The UC San Diego scientists prepared melanin-like nanoparticles through the spontaneous oxidation of dopamine—developing biocompatible, synthetic analogues of naturally occurring melanosomes. Then they studied their update, transport, distribution and ultraviolet radiation-protective capabilities in human keratinocytes in tissue culture.

The researchers found that these synthetic nanoparticles were not only taken up and distributed normally, like natural melanosomes, within the keratinocytes, they protected the skin cells from DNA damage due to ultraviolet radiation.

“Considering limitations in the treatment of melanin-defective related diseases and the biocompatibility of these synthetic melanin-like nanoparticles in terms of uptake and degradation, these systems have potential as artificial melanosomes for the development of novel therapies, possibly supplementing the biological functions of natural melanins,” the researchers said in their paper.

The other co-authors of the study were Yuran Huang and Ziying Hu of UC San Diego’s Materials Science and Engineering Program, Yiwen Li and Maria Proetto of the Department of Chemistry and Biochemistry; Xiujun Yue of the Department of Nanoengineering; and Ying Jones of the Electron Microscopy Core Facility.

The UC San Diego Office of Innovation and Commercialization has filed a patent application on the use of polydopamine-based artificial melanins as an intracellular UV-shield. Companies interested in commercializing this invention should contact Skip Cynar at invent@ucsd.edu

Here’s a link to and a citation fro the paper,

Mimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols by
Yuran Huang, Yiwen Li, Ziying Hu, Xiujun Yue, Maria T. Proetto, Ying Jones, and Nathan C. Gianneschi. ACS Cent. Sci., Article ASAP DOI: 10.1021/acscentsci.6b00230 Publication Date (Web): May 18, 2017

Copyright © 2017 American Chemical Society

This is an open access paper,

Using melanin in bioelectronic devices

Brazilian researchers are working with melanin to make biosensors and other bioelectronic devices according to a Dec. 20, 2016 news item on phys.org,

Bioelectronics, sometimes called the next medical frontier, is a research field that combines electronics and biology to develop miniaturized implantable devices capable of altering and controlling electrical signals in the human body. Large corporations are increasingly interested: a joint venture in the field has recently been announced by Alphabet, Google’s parent company, and pharmaceutical giant GlaxoSmithKline (GSK).

One of the challenges that scientists face in developing bioelectronic devices is identifying and finding ways to use materials that conduct not only electrons but also ions, as most communication and other processes in the human organism use ionic biosignals (e.g., neurotransmitters). In addition, the materials must be biocompatible.

Resolving this challenge is one of the motivations for researchers at São Paulo State University’s School of Sciences (FC-UNESP) at Bauru in Brazil. They have succeeded in developing a novel route to more rapidly synthesize and to enable the use of melanin, a polymeric compound that pigments the skin, eyes and hair of mammals and is considered one of the most promising materials for use in miniaturized implantable devices such as biosensors.

A Dec. 14, 2016 FAPESP (São Paulo Research Foundation) press release, which originated the news item, further describes both the research and a recent meeting where the research was shared (Note: A link has been removed),

Some of the group’s research findings were presented at FAPESP Week Montevideo during a round-table session on materials science and engineering.

The symposium was organized by the Montevideo Group Association of Universities (AUGM), Uruguay’s University of the Republic (UdelaR) and FAPESP and took place on November 17-18 at UdelaR’s campus in Montevideo. Its purpose was to strengthen existing collaborations and establish new partnerships among South American scientists in a range of knowledge areas. Researchers and leaders of institutions in Uruguay, Brazil, Argentina, Chile and Paraguay attended the meeting.

“All the materials that have been tested to date for applications in bioelectronics are entirely synthetic,” said Carlos Frederico de Oliveira Graeff, a professor at UNESP Bauru and principal investigator for the project, in an interview given to Agência FAPESP.

“One of the great advantages of melanin is that it’s a totally natural compound and biocompatible with the human body: hence its potential use in electronic devices that interface with brain neurons, for example.”

Application challenges

According to Graeff, the challenges of using melanin as a material for the development of bioelectronic devices include the fact that like other carbon-based materials, such as graphene, melanin is not easily dispersible in an aqueous medium, a characteristic that hinders its application in thin-film production.

Furthermore, the conventional process for synthesizing melanin is complex: several steps are hard to control, it can last up to 56 days, and it can result in disorderly structures.

In a series of studies performed in recent years at the Center for Research and Development of Functional Materials (CDFM), where Graeff is a leading researcher and which is one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP, he and his collaborators managed to obtain biosynthetic melanin with good dispersion in water and a strong resemblance to natural melanin using a novel synthesis route.

The process developed by the group at CDMF takes only a few hours and is based on changes in parameters such as temperature and the application of oxygen pressure to promote oxidation of the material.

By applying oxygen pressure, the researchers were able to increase the density of carboxyl groups, which are organic functional groups consisting of a carbon atom double bonded to an oxygen atom and single bonded to a hydroxyl group (oxygen + hydrogen). This enhances solubility and facilitates the suspension of biosynthetic melanin in water.

“The production of thin films of melanin with high homogeneity and quality is made far easier by these characteristics,” Graeff said.

By increasing the density of carboxyl groups, the researchers were also able to make biosynthetic melanin more similar to the biological compound.

In living organisms, an enzyme that participates in the synthesis of melanin facilitates the production of carboxylic acids. The new melanin synthesis route enabled the researchers to mimic the role of this enzyme chemically while increasing carboxyl group density.

“We’ve succeeded in obtaining a material that’s very close to biological melanin by chemical synthesis and in producing high-quality film for use in bioelectronic devices,” Graeff said.

Through collaboration with colleagues at research institutions in Canada [emphasis mine], the Brazilian researchers have begun using the material in a series of applications, including electrical contacts, pH sensors and photovoltaic cells.

More recently, they have embarked on an attempt to develop a transistor, a semiconductor device used to amplify or switch electronic signals and electrical power.

“Above all, we aim to produce transistors precisely in order to enhance this coupling of electronics with biological systems,” Graeff said.

I’m glad to have gotten some information about the work in South America. It’s one of FrogHeart’s shortcomings that I have so little about the research in that area of the world. I believe this is largely due to my lack of Spanish language skills. Perhaps one day there’ll be a universal translator that works well. In the meantime, it was a surprise to see Canada mentioned in this piece. I wonder which Canadian research institutions are involved with this research in South America.

Adding melanin to make foams and fabrics stronger

Melanin does not have a reputation as a strengthening agent so why these scientists tested it for that purpose is a mystery. From a Nov. 9, 2016 news item on phys.org,

Melanin is the natural molecule in animals’ skin, hair and the iris of eyes that gives them color and helps protect them from ultraviolet light. Someday soon, the pigment could be found in unexpected places such as sofa cushions or clothing—but not for its hue. Scientists have found that adding a small amount of melanin to polyurethane makes it far stronger than the material by itself. …

A Nov. 9, 2016 American Chemical Society (ACS) press release (also on EurekAlert), which originated the news item, expands on the theme,

From durable foam seating and insulation to glossy coatings and stretchy textiles, polyurethane is used in a huge range of products. Although already fairly versatile, polyurethane still has room for improvement. To make it more durable, scientists have tried adding fillers, including silica, carbon nanotubes and graphene oxide. But these efforts have often led to the enhancement of only one physical property at a time, such as tensile strength — how hard a material can be pulled before it snaps — but not toughness — how much energy it can absorb without breaking. Mingqing Chen, Weifu Dong and colleagues wanted to try a new approach: adding melanin, a biomolecule increasingly used in various other materials.

The researchers found that polyurethane containing just 2 percent melanin, extracted from the ink sacs of cuttlefish, had improved tensile strength and toughness. These properties were enhanced about 10 fold, increasing from 5.6 megapascals and 33 megajoules per cubic meter in plain polyurethane to 51.5 MPa and 413 MJ/m3, respectively. Polyurethane by itself could stretch 770 percent before breaking, whereas the melanin-infused version stretched 1,880 percent before rupturing.

Here’s a link to and a citation for the paper,

Superior Performance of Polyurethane Based on Natural Melanin Nanoparticles by Yang Wang, Ting Li, Xuefei Wang, Piming Ma, Huiyu Bai, Weifu Dong, Yi Xie, and Mingqing Chen. Biomacromolecules, DOI: 10.1021/acs.biomac.6b01298 Publication Date (Web): October 17, 2016

Copyright © 2016 American Chemical Society

This paper is behind a paywall.