Tag Archives: nanofactories

Ginger nanoparticles for inflammatory bowel disease

I guess we’ll have to add ginger to the list of folk medicines (tumeric is another) which are being discovered by nanomedicine. An Aug. 17, 2016 news item on ScienceDaily describes the ‘ginger’ research at the US Dept. of Veterans Affairs,

A recent study by researchers at the Atlanta Veterans Affairs Medical Center took them to a not-so-likely destination: local farmers markets. They went in search of fresh ginger root.

Back at the lab, the scientists turned the ginger into what they are calling GDNPs, or ginger-derived nanoparticles. The process started simply enough, with your basic kitchen blender. But then it involved super-high-speed centrifuging and ultrasonic dispersion of the ginger juice, to break it up into single pellets. (Don’t try this at home!)

The research team, led by Dr. Didier Merlin with VA and the Institute for Biomedical Sciences at Georgia State University, believes the particles may be good medicine for Crohn’s disease and ulcerative colitis, the two main forms of inflammatory bowel disease (IBD). The particles may also help fight cancer linked to colitis, the scientists believe.

An Aug. 16, 2016 US Dept. of Veterans Affairs news release (also on EurekAlert), which originated the news item, provides more detail about the research,

Each ginger-based nanoparticle was about 230 nanometers in diameter. More than 300 of them could fit across the width of a human hair.

Fed to lab mice, the particles appeared to be nontoxic and had significant therapeutic effects:

  • Importantly, they efficiently targeted the colon. They were absorbed mainly by cells in the lining of the intestines, where IBD inflammation occurs.
  • The particles reduced acute colitis and prevented chronic colitis and colitis-associated cancer.
  • They enhanced intestinal repair. Specifically, they boosted the survival and proliferation of the cells that make up the lining of the colon. They also lowered the production of proteins that promote inflammation, and raised the levels of proteins that fight inflammation.

Part of the therapeutic effect, say the researchers, comes from the high levels of lipids–fatty molecules–in the particles, a result of the natural lipids in the ginger plant. One of the lipids is phosphatidic acid, an important building block of cell membranes.

The particles also retained key active constituents found naturally in ginger, such as 6-gingerol and 6-shogaol. Past lab studies have shown the compounds to be active against oxidation, inflammation, and cancer. They are what make standard ginger an effective remedy for nausea and other digestion problems. Traditional cultures have used ginger medicinally for centuries, and health food stores carry ginger-based supplements–such as chews, or the herb mixed with honey in a syrup–as digestive aids.

Delivering these compounds in a nanoparticle, says Merlin’s team, may be a more effective way to target colon tissue than simply providing the herb as a food or supplement.

The idea of fighting IBD with nanoparticles is not new. In recent years, Merlin’s lab and others have explored how to deliver conventional drugs via nanotechnology. Some of this research is promising. The approach may allow low doses of drugs to be delivered only where they are needed–inflamed tissue in the colon–and thus avoid unwanted systemic effects.

The advantage of ginger, say the researchers, is that it’s nontoxic, and could represent a very cost-effective source of medicine.

The group is looking at ginger, and other plants, as potential “nanofactories for the fabrication of medical nanoparticles.”

Merlin and his VA and Georgia State University coauthors elaborated on the idea in a report earlier this year titled “Plant-derived edible nanoparticles as a new therapeutic approach against diseases.” They wrote that plants are a “bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles.”

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

Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer by Mingzhen Zhang, Emilie Viennois, Meena Prasad, Yunchen Zhang, Lixin Wang, Zhan Zhang, Moon Kwon Han, Bo Xiao, Changlong Xu, Shanthi Srinivasan, Didier Merlin. Biomaterials Volume 101, September 2016, Pages 321–340         doi:10.1016/j.biomaterials.2016.06.018

This paper is behind a paywall.

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

Plant derived edible nanoparticles as a new therapeutic approach against diseases by Mingzhen Zhang, Emilie Viennois, Changlong Xu, & Didier Merlin. Tissue Barriers Volume 4, 2016 – Issue 2  http://dx.doi.org/10.1080/21688370.2015.1134415 Published online: 11 Feb 2016

This paper too is behind a paywall.

An entire chemistry lab (nanofactory) in a droplet

I love the blue in this image, which illustrates the thousand-droplets test, research suggesting the possibility of a nanofactory or laboratory within a droplet ,

Droplets with a diameter of only a few micrometers act as the reaction vessels for a complex oscillating reaction - Photo: Maximilian Weitz / TUM

Droplets with a diameter of only a few micrometers act as the reaction vessels for a complex oscillating reaction – Photo: Maximilian Weitz / TUM

A Feb. 19, 2014 news item on Azonano reveals more,

An almost infinite number of complex and interlinked reactions take place in a biological cell. In order to be able to better investigate these networks, scientists led by Professor Friedrich Simmel, Chair of Systems Biophysics and Nano Biophysics at the Technische Universitaet Muenchen (TUM) try to replicate them with the necessary components in a kind of artificial cell.

This is also motivated by the thought of one day using such single-cell systems for example as “nanofactories” for the production of complex organic substances or biomaterials.

All such experiments have so far predominantly worked with very simple reactions, however. NIM Professor Friedrich Simmel and his team have now for the first time managed to let a more complex biochemical reaction take place in tiny droplets of only a few micrometers in size. Together with co-authors from the University of California Riverside and the California Institute of Technology in Pasadena, USA, the scientists are presenting their findings in the current edition of Nature Chemistry.

The Feb. 18, 2014 TUM press release, which originated the news item, details the experiements,

Shaking once – investigating thousands of times

The experiment is conducted by putting an aqueous reaction solution into oil and shaking the mixture vigorously. The result is an emulsion consisting of thousands of droplets. Employing only a tiny amount of material, the scientists have thus found a cost-efficient and quick way of setting up an extremely large number of experiments simultaneously.

As a test system, the researchers chose a so-called biochemical oscillator. This involves several reactions with DNA and RNA, which take place repetitively one after the other. Their rhythm becomes visible because in one step two DNA strands bind to each other in such a way that a fluorescent dye shines. This regular blinking is then recorded with special cameras.

Small droplets – huge differences

In the first instance, Friedrich Simmel and his colleagues intended to investigate the principal behavior of a complex reaction system if scaled down to the size of a cell. In addition, they specifically wondered if all droplet systems displayed an identical behavior and what factors would cause possible differences.

Their experiments showed that the oscillations in the individual droplets differed strongly, that is to say, much stronger than might have been expected from a simple statistical model. It was above all evident that small drops display stronger variations than large ones. “It is indeed surprising that we could witness a similar variability and individuality in a comparatively simple chemical system as is known from biological cells”, explains Friedrich Simmel the results.

Thus, it is currently not possible to realize systems which are absolutely identical. This de facto means that researchers have to either search for ways to correct these variations or factor them in from the start. On the other hand, the numerous slightly differing systems could also be used specifically to pick out the one desired, optimally running set-up from thousands of systems.

Investigating complex biosynthetic systems in artificial cells opens up many other questions, as well. In a next step, Friedrich Simmel plans to address the underlying theoretical models: “The highly parallel recording of the emulsion droplets enabled us to acquire plenty of interesting data. Our goal is to use these data to review and improve the theoretical models of biochemical reaction networks at small molecule numbers.”

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

Diversity in the dynamical behaviour of a compartmentalized programmable biochemical oscillator by Maximilian Weitz, Jongmin Kim, Korbinian Kapsner, Erik Winfree, Elisa Franco, & Friedrich C. Simmel. Nature Chemistry (2014) doi:10.1038/nchem.1869 Published online 16 February 2014

This paper is behind a paywall.