Tag Archives: biocompatibility

Observing individual silver nanoparticles in real time

A new technique for better understanding how silver nanoparticles might affect the environment was announced in a July 30, 2018 news item on ScienceDaily,

Chemists at Ruhr-Universität Bochum have developed a new method of observing the chemical reactions of individual silver nanoparticles, which only measure a thousandth of the thickness of a human hair, in real time. The particles are used in medicine, food and sports items because they have an antibacterial and anti-inflammatory effect. However, how they react and degrade in ecological and biological systems is so far barely understood. The team in the Research Group for Electrochemistry and Nanoscale Materials showed that the nanoparticles transform into poorly soluble silver chloride particles under certain conditions. The group led by Prof Dr Kristina Tschulik reports on the results in the Journal of the American Chemical Society from July 11, 2018.

A July 30,2018 Ruhr-University Bochum (RUB) press release (also on EurekAlert) by Julia Weiler, which originated the news item, provides more information,

Even under well-defined laboratory conditions, current research has yielded different, sometimes contradictory, results on the reaction of silver nanoparticles. “In every batch of nanoparticles, the individual properties of the particles, such as size and shape, vary,” says Kristina Tschulik, a member of the Cluster of Excellence Ruhr Explores Solvation. “With previous procedures, a myriad of particles was generally investigated at the same time, meaning that the effects of these variations could not be recorded. Or the measurements took place in a high vacuum, not under natural conditions in an aqueous solution.”

The team led by Kristina Tschulik thus developed a method that enables individual silver particles to be investigated in a natural environment. “Our aim is to be able to record the reactivity of individual particles,” explains the researcher. This requires a combination of electrochemical and spectroscopic methods. With optical and hyperspectral dark-field microscopy, the group was able to observe individual nanoparticles as visible and coloured pixels. Using the change in the colour of the pixels, or more precisely their spectral information, the researchers were able to follow what was happening in an electrochemical experiment in real time.

Degradation of the particles slowed down

In the experiment, the team replicated the oxidation of silver in the presence of chloride ions, which often takes place in ecological and biological systems. “Until now, it was generally assumed that the silver particles dissolve in the form of silver ions,” describes Kristina Tschulik. However, poorly soluble silver chloride was formed in the experiment – even if only a few chloride ions were present in the solution.

“This extends the lifespan of the nanoparticles to an extreme extent and their breakdown is slowed down in an unexpectedly drastic manner,” summarises Tschulik. “This is equally important for bodies of water and for living beings because this mechanism could cause the heavy metal silver to accumulate locally, which can be toxic for many organisms.”

Further development planned

The Bochum-based group now wants to further improve its technology for analysing individual nanoparticles in order to better understand the ageing mechanisms of such particles. The researchers thus want to obtain more information about the biocompatibility of the silver particles and the lifespan and ageing of catalytically active nanoparticles in the future.

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

Simultaneous Opto- and Spectro-Electrochemistry: Reactions of Individual Nanoparticles Uncovered by Dark-Field Microscopy by Kevin Wonner, Mathies V. Evers, and Kristina Tschulik. J. Am. Chem. Soc., Article ASAP DOI: 10.1021/jacs.8b02367 Publication Date (Web): July 11, 2018

Copyright © 2018 American Chemical Society

This paper is behind a paywall.

Calligraphy ink and cancer treatment

Courtesy of ACS Omega and the researchers

Nice illustration! I wish I could credit the artist. For anyone who needs a little text to make sense of it, there’s a Sept. 27, 2017 news item on Nanowerk (Note: A link has been removed),

For hundreds of years, Chinese calligraphers have used a plant-based ink to create beautiful messages and art. Now, one group reports in ACS Omega (“New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes”) that this ink could noninvasively and effectively treat cancer cells that spread, or metastasize, to lymph nodes.

A Sept. 27, 2017 American Chemical Society (ACS) news release, which originated the news item, reveals more about the research,

As cancer cells leave a tumor, they frequently make their way to lymph nodes, which are part of the immune system. In this case, the main treatment option is surgery, but this can result in complications. Photothermal therapy (PTT) is an emerging noninvasive treatment option in which nanomaterials are injected and accumulate in cancer cells. A laser heats up the nanomaterials, and this heat kills the cells. Many of these nanomaterials are expensive, difficult-to-make and toxic. However, a traditional Chinese ink called Hu-Kaiwen ink (Hu-ink) has similar properties to the nanomaterials used in PTT. For example, they are the same color, and are both carbon-based and stable in water. So Wuli Yang and colleagues wanted to see if Hu-ink could be a good alternative material for PTT.

The researchers analyzed Hu-ink and found that it consists of nanoparticles and thin layers of carbon. When Hu-ink was heated with a laser, its temperature rose by 131 degrees Fahrenheit, much higher than current nanomaterials. Under PPT conditions, the Hu-ink killed cancer cells in a laboratory dish, but under normal conditions, the ink was non-toxic. This was also the scenario observed in mice with tumors. The researchers also noted that Hu-ink could act as a probe to locate tumors and metastases because it absorbs near-infrared light, which goes through skin.

Being a little curious about Hu-ink’s similarity to nanomaterial, I looked for more detail in the the paper (Note: Links have been removed), From the: Introduction,

Photothermal therapy (PTT) is an emerging tumor treatment strategy, which utilizes hyperthermia generated from absorbed near-infrared (NIR) light energy by photoabsorbing agents to kill tumor cells.(7-13) Different from chemotherapy, surgical treatment, and radiotherapy, PTT is noninvasive and more efficient.(7, 14, 15) In the past decade, PTT with diverse nanomaterials to eliminate cancer metastases lymph nodes has attracted extensive attention by several groups, including our group.(3, 16-20) For instance, Liu and his co-workers developed a treatment method based on PEGylated single-walled carbon nanotubes for PTT of tumor sentinel lymph nodes and achieved remarkably improved treatment effect in an animal tumor model.(21) To meet the clinical practice, the potential metastasis of deeper lymph nodes was further ablated in our previous work, using magnetic graphene oxide as a theranostic agent.(22) However, preparation of these artificial nanomaterials usually requires high cost, complicated synthetic process, and unavoidably toxic catalyst or chemicals,(23, 24) which impede their future clinical application. For the clinical application, exploring an environment-friendly material with simple preparation procedure, good biocompatibility, and excellent therapeutic efficiency is still highly desired. [emphases mine]

From the: Preparation and Characterization of Hu-Ink

To obtain an applicable sample, the condensed Hu-ink was first diluted into aqueous dispersion with a lower concentration. The obtained Hu-ink dispersion without any further treatment was black in color and stable in physiological environment, including water, phosphate-buffered saline (PBS), and Roswell Park Memorial Institute (RPMI) 1640; furthermore, no aggregation was observed even after keeping undisturbed for 3 days (Figure 2a). The nanoscaled morphology of Hu-ink was examined by transmission electron microscopy (TEM) (Figure 2b), which demonstrates that Hu-ink mainly exist in the form of small aggregates. These small aggregates consist of a few nanoparticles with diameter of about 20–50 nm. Dynamic light scattering (DLS) measurement (Figure 2c) further shows that Hu-ink aqueous dispersion possesses a hydrodynamic diameter of about 186 nm (polydispersity index: 0.18), which was a crucial prerequisite for biomedical applications.(29) In the X-ray diffraction (XRD) pattern, no other characteristic peaks are found except carbon peak (Figure S1, Supporting Information), which confirms that the main component of Hu-ink is carbon.(25) Raman spectroscopy was a common tool to characterize graphene-related materials.(30) D band (∼1300 cm–1, corresponding to the defects) and G band (∼1600 cm–1, related to the sp2 carbon sites) peaks could be observed in Figure 2d with the ratio ID/IG = 0.96, which confirms the existence of graphene sheetlike structure in Hu-ink.(31) The UV–vis–NIR spectra (Figure 2e) also revealed that Hu-ink has high absorption in the NIR region around 650–900 nm, in which hemoglobin and water, the major absorbers of biological tissue, have their lowest absorption coefficient.(32) The high NIR absorption capability of Hu-ink encouraged us to investigate its photothermal properties.(33-35) Hu-ink dispersions with different concentrations were irradiated under an 808 nm laser (the commercial and widely used wavelength in photothermal therapy).(8-13) [emphases mine]

Curiosity satisfied! For those who’d like to investigate even further, here’s a link to and a citation for the paper,

New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes by Sheng Wang, Yongbin Cao, Qin Zhang, Haibao Peng, Lei Liang, Qingguo Li, Shun Shen, Aimaier Tuerdi, Ye Xu, Sanjun Cai, and Wuli Yang. ACS Omega, 2017, 2 (8), pp 5170–5178 DOI: 10.1021/acsomega.7b00993 Publication Date (Web): August 30, 2017

Copyright © 2017 American Chemical Society

This paper appears to be open access.

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.

Graphene ribbons in solution bending and twisting like DNA

An Aug. 15, 2016 news item on ScienceDaily announces research into graphene nanoribbons and their DNA (deoxyribonucleic acid)-like properties,

Graphene nanoribbons (GNRs) bend and twist easily in solution, making them adaptable for biological uses like DNA analysis, drug delivery and biomimetic applications, according to scientists at Rice University.

Knowing the details of how GNRs behave in a solution will help make them suitable for wide use in biomimetics, according to Rice physicist Ching-Hwa Kiang, whose lab employed its unique capabilities to probe nanoscale materials like cells and proteins in wet environments. Biomimetic materials are those that imitate the forms and properties of natural materials.

An Aug. 15, 2016 Rice University (Texas, US) news release (also on EurekAlert), which originated the news item, describes the ribbons and the research in more detail,

Graphene nanoribbons can be thousands of times longer than they are wide. They can be produced in bulk by chemically “unzipping” carbon nanotubes, a process invented by Rice chemist and co-author James Tour and his lab.

Their size means they can operate on the scale of biological components like proteins and DNA, Kiang said. “We study the mechanical properties of all different kinds of materials, from proteins to cells, but a little different from the way other people do,” she said. “We like to see how materials behave in solution, because that’s where biological things are.” Kiang is a pioneer in developing methods to probe the energy states of proteins as they fold and unfold.

She said Tour suggested her lab have a look at the mechanical properties of GNRs. “It’s a little extra work to study these things in solution rather than dry, but that’s our specialty,” she said.

Nanoribbons are known for adding strength but not weight to solid-state composites, like bicycle frames and tennis rackets, and forming an electrically active matrix. A recent Rice project infused them into an efficient de-icer coating for aircraft.

But in a squishier environment, their ability to conform to surfaces, carry current and strengthen composites could also be valuable.

“It turns out that graphene behaves reasonably well, somewhat similar to other biological materials. But the interesting part is that it behaves differently in a solution than it does in air,” she said. The researchers found that like DNA and proteins, nanoribbons in solution naturally form folds and loops, but can also form helicoids, wrinkles and spirals.

Kiang, Wijeratne [Sithara Wijeratne, Rice graduate now a postdoctoral researcher at Harvard University] and Jingqiang Li, a co-author and student in the Kiang lab, used atomic force microscopy to test their properties. Atomic force microscopy can not only gather high-resolution images but also take sensitive force measurements of nanomaterials by pulling on them. The researchers probed GNRs and their precursors, graphene oxide nanoribbons.

The researchers discovered that all nanoribbons become rigid under stress, but their rigidity increases as oxide molecules are removed to turn graphene oxide nanoribbons into GNRs. They suggested this ability to tune their rigidity should help with the design and fabrication of GNR-biomimetic interfaces.

“Graphene and graphene oxide materials can be functionalized (or modified) to integrate with various biological systems, such as DNA, protein and even cells,” Kiang said. “These have been realized in biological devices, biomolecule detection and molecular medicine. The sensitivity of graphene bio-devices can be improved by using narrow graphene materials like nanoribbons.”

Wijeratne noted graphene nanoribbons are already being tested for use in DNA sequencing, in which strands of DNA are pulled through a nanopore in an electrified material. The base components of DNA affect the electric field, which can be read to identify the bases.

The researchers saw nanoribbons’ biocompatibility as potentially useful for sensors that could travel through the body and report on what they find, not unlike the Tour lab’s nanoreporters that retrieve information from oil wells.

Further studies will focus on the effect of the nanoribbons’ width, which range from 10 to 100 nanometers, on their properties.

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

Detecting the Biopolymer Behavior of Graphene Nanoribbons in Aqueous Solution by Sithara S. Wijeratne, Evgeni S. Penev, Wei Lu, Jingqiang Li, Amanda L. Duque, Boris I. Yakobson, James M. Tour, & Ching-Hwa Kiang. Scientific Reports 6, Article number: 31174 (2016)  doi:10.1038/srep31174 Published online: 09 August 2016

This paper is open access.

Nanotechnology and biocompatibility; carbon nanotubes in agriculture; venture capital for nanotechnology

One of the big nanotechnology toxicity issues centers around the question of its biocompatibility i.e. what effect do the particles have on cells in human bodies, plants, and other biological organisms? Right now, the results are mixed. Two studies have recently been published which suggest that there are neutral or even positive responses to nanoparticles.

Researchers at Lund University (Sweden) have conducted tests of nanowires, which they are hoping could be used as electrodes in the future, showing that microglial cells break down the nanowires and almost completely clean them away over a period of weeks. You can read more about the work here on Nanowerk. I would expect they’ll need to do more studies confirming these results as well more tests establishing what happens to the nanowire debris over longer periods of time and what problems, if any, emerge when electrodes are introduced in succession (i.e. how many times can you implant nanowires and have them ‘mostly’ cleaned away?).

The other biocompatibility story centers on food stuffs. Apparently carbon nanotubes can have a positive effect on crops. According to researchers in Arkansas*, Mariya Khodakovskaya, Alexandru Biris, and their colleagues, the treated seeds (tomato) sprouted twice as fast and grew more than twice as much as their untreated neighbours. The news item is here on Nanowerk and there is a more in-depth article about agriculture and nanotechnology here in Nanowerk Spotlight. (Note: I have checked and both of the papers have been published although I believe they’re both behind paywalls.)

It seems be to a Nanowerk day as I’m featuring the site again for this item. They have made a guide to finding venture capital for startup nanotechnology companies available on their site. From the item,

To help potential nanotechnology start-up founders with shaping their plans, Nanowerk, the leading nanotechnology information service, and Nanostart, the world’s leading nanotechnology venture capital company, have teamed up to provide this useful guide which particularly addresses the funding aspects of nanotechnology start-ups, along with answers to some of the most commonly asked questions.

You can read more here.

*’Arkansaa’ corrected to ‘Arkansas’ on Dec. 7, 2017.