Tag Archives: Peng Mi

pH dependent nanoparticle-based contrast agent for MRIs (magnetic resonance images)

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This news about a safer and more effective contrast agent for MRIs (magnetic resonance images) developed by Japanese scientists come from a June 6, 2016 article by Heather Zeiger on phys.org. First some explanations,

Magnetic resonance imaging relies on the excitation and subsequent relaxation of protons. In clinical MRI studies, the signal is determined by the relaxation time of the hydrogen protons in water. To get a stronger signal, scientists can use contrast agents to shorten the relaxation time of the protons.

MRI is non-invasive and does not involve radiation, making it a safe diagnostic tool. However, its weak signal makes tumor detection difficult. The ideal contrast agent would select for malignant tumors, making its location and diagnosis much more obvious.

Nanoparticle contrast agents have been of interested because nanoparticles can be functionalized and, as in this study, can contain various metals. Researchers have attempted to functionalize nanoparticles with ligands that attach to chemical factors on the surface of cancer cells. However, cancer cells tend to be compositionally heterogeneous, leading some researchers to look for nanoparticles that respond to differences in pH or redox potential compared to normal cells.

Now for the research,

Researchers from the University of Tokyo, Tokyo Institute of Technology, Kawasaki Institute of Industry Promotion, and the Japan Agency for Quantum and Radiological Science and Technology have developed a contrast agent from calcium phosphate-based nanoparticles that release a manganese ion an acidic environment. …

Peng Mi, Daisuke Kokuryo, Horacio Cabral, Hailiang Wu, Yasuko Terada, Tsuneo Saga, Ichio Aoki, Nobuhiro Nishiyama, and Kazunori Kataoka developed a contrast agent that is comprised of Mn2+– doped CaP nanoparticles with a PEG shell. They reasoned that using CaP nanoparticles, which are known to be pH sensitive, would allow the targeted release of Mn2+ ions in the tumor microenvironment. The tumor microenvironment tends to have a lower pH than the normal regions to rapid cell metabolism in an oxygen-depleted environment. Manganese ions were tested because they are paramagnetic, which makes for a good contrast agent. They also bind to proteins creating a slowly rotating manganese-protein system that results in sharp contrast enhancement.

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These results were promising, so Peng Mi, et al. then tested whether the CaPMnPEG contrast agent worked in solid tumors. Because Mn2+ remains confined within the nanoparticle matrix at physiological pH, CaPMnPEG demonstrate a much lower toxicity [emphasis mine] compared to MnCl2. MRI studies showed a tumor-to-normal contrast of 131% after 30 minute, which is much higher than Gd-DTPA [emphasis mine], a clinically approved contrast agent. After an hour, the tumor-to-normal ratio was 160% and remained around 170% for several hours.

Three-dimensional MRI studies of solid tumors showed that without the addition of CaPMnPEG, only blood vessels were visible. However, upon adding CaPMnPEG, the tumor was easily distinguishable. Additionally, there is evidence that excess Mn2+ leaves the plasma after an hour. The contrast signal remained strong for several hours indicating that protein binding rather than Mn2+ concentration is important for signal enhancement.

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Finally, tests with metastatic tumors in the liver (C26 colon cancer cells) showed that CaPMnPEG works well in solid organ analysis and is highly sensitive to detecting millimeter-sized micrometastasis [emphasis mine]. Unlike other contrast agents used in the clinic, CaPMnPEG provided a contrast signal that lasted for several hours after injection. After an hour, the signal was enhanced by 25% and after two hours, the signal was enhanced by 39%.

This is exciting stuff. Bravo to the researchers!

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

A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy by Peng Mi, Daisuke Kokuryo, Horacio Cabral, Hailiang Wu, Yasuko Terada, Tsuneo Saga, Ichio Aoki, Nobuhiro Nishiyama, & Kazunori Kataoka. Nature Nanotechnology (2016) doi:10.1038/nnano.2016.72 Published online 16 May 2016

This paper is behind a paywall.

A city of science in Japan: Kawasaki (Kanagawa)

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Happily, I’m getting more nanotechnology (for the most part) information from Japan. Given Japan’s prominence in this field of endeavour I’ve long felt FrogHeart has not adequately represented Japanese contributions. Now that I’m receiving English language translations, I hope to better address the situation.

This morning (March 26, 2015), there were two news releases from Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT), Coastal Area International Strategy Office, Kawasaki City, Japan in my mailbox. Before getting on to the news releases, here’s a little about  the city of Kawasaki and about its innovation gateway. From the Kawasaki, Kanagawa entry in Wikipedia (Note: Links have been removed),

Kawasaki (川崎市 Kawasaki-shi?) is a city in Kanagawa Prefecture, Japan, located between Tokyo and Yokohama. It is the 9th most populated city in Japan and one of the main cities forming the Greater Tokyo Area and Keihin Industrial Area.

Kawasaki occupies a belt of land stretching about 30 kilometres (19 mi) along the south bank of the Tama River, which divides it from Tokyo. The eastern end of the belt, centered on JR Kawasaki Station, is flat and largely consists of industrial zones and densely built working-class housing, the Western end mountainous and more suburban. The coastline of Tokyo Bay is occupied by vast heavy industrial complexes built on reclaimed land.

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There is a 2014 video about Kawasaki’s innovation gateway, which despite its 14 mins. 39 secs. running time I am embedding here. (Caution: They highlight their animal testing facility at some length.)

Now on to the two news releases. The first concerns research on gold nanoparticles that was published in 2014. From a March 26, 2015 Kawasaki INnovation Gateway news release,

Gold nanoparticles size up to cancer treatment

Incorporating gold nanoparticles helps optimise treatment carrier size and stability to improve delivery of cancer treatment to cells.

Treatments that attack cancer cells through the targeted silencing of cancer genes could be developed using small interfering RNA molecules (siRNA). However delivering the siRNA into the cells intact is a challenge as it is readily degraded by enzymes in the blood and small enough to be eliminated from the blood stream by kidney filtration.  Now Kazunori Kataoka at the University of Tokyo and colleagues at Tokyo Institute of Technology have designed a protective treatment delivery vehicle with optimum stability and size for delivering siRNA to cells.

The researchers formed a polymer complex with a single siRNA molecule. The siRNA-loaded complex was then bonded to a 20 nm gold nanoparticle, which thanks to advances in synthesis techniques can be produced with a reliably low size distribution. The resulting nanoarchitecture had the optimum overall size – small enough to infiltrate cells while large enough to accumulate.

In an assay containing heparin – a biological anti-coagulant with a high negative charge density – the complex was found to release the siRNA due to electrostatic interactions. However when the gold nanoparticle was incorporated the complex remained stable. Instead, release of the siRNA from the complex with the gold nanoparticle could be triggered once inside the cell by the presence of glutathione, which is present in high concentrations in intracellular fluid. The glutathione bonded with the gold nanoparticles and the complex, detaching them from each other and leaving the siRNA prone to release.

The researchers further tested their carrier in a subcutaneous tumour model. The authors concluded that the complex bonded to the gold nanoparticle “enabled the efficient tumor accumulation of siRNA and significant in vivo gene silencing effect in the tumor, demonstrating the potential for siRNA-based cancer therapies.”

The news release provides links to the March 2015 newsletter which highlights this research and to the specific article and video,

March 2015 Issue of Kawasaki SkyFront iNewsletter: http://inewsletter-king-skyfront.jp/en/

Contents

Feature video on Professor Kataoka’s research : http://inewsletter-king-skyfront.jp/en/video_feature/vol_3/feature01/

Research highlights: http://inewsletter-king-skyfront.jp/en/research_highlights/vol_3/research01/

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

Precise Engineering of siRNA Delivery Vehicles to Tumors Using Polyion Complexes and Gold Nanoparticles by Hyun Jin Kim, Hiroyasu Takemoto, Yu Yi, Meng Zheng, Yoshinori Maeda, Hiroyuki Chaya, Kotaro Hayashi, Peng Mi, Frederico Pittella, R. James Christie, Kazuko Toh, Yu Matsumoto, Nobuhiro Nishiyama, Kanjiro Miyata, and Kazunori Kataoka. ACS Nano, 2014, 8 (9), pp 8979–8991 DOI: 10.1021/nn502125h Publication Date (Web): August 18, 2014
Copyright © 2014 American Chemical Society

This article is behind a paywall.

The second March 26, 2015 Kawasaki INnovation Gateway news release concerns a DNA chip and food-borne pathogens,

Rapid and efficient DNA chip technology for testing 14 major types of food borne pathogens

Conventional methods for testing food-borne pathogens is based on the cultivation of pathogens, a process that is complicated and time consuming. So there is demand for alternative methods to test for food-borne pathogens that are simpler, quick and applicable to a wide range of potential applications.

Now Toshiba Ltd and Kawasaki City Institute for Public Health have collaborated in the development of a rapid and efficient automatic abbreviated DNA detection technology that can test for 14 major types of food borne pathogens. The so called ‘DNA chip card’ employs electrochemical DNA chips and overcomes the complicated procedures associated with genetic testing of conventional methods. The ‘DNA chip card’ is expected to find applications in hygiene management in food manufacture, pharmaceuticals, and cosmetics.

Details

The so-called automatic abbreviated DNA detection technology ‘DNA chip card’ was developed by Toshiba Ltd and in a collaboration with Kawasaki City Institute for Public Health, used to simultaneously detect 14 different types of food-borne pathogens in less than 90 minutes. The detection sensitivity depends on the target pathogen and has a range of 1E+01~05 cfu/mL.

Notably, such tests would usually take 4-5 days using conventional methods based on pathogen cultivation. Furthermore, in contrast to conventional DNA protocols that require high levels of skill and expertise, the ‘DNA chip card’ only requires the operator to inject nucleic acid, thereby making the procedure easier to use and without specialized operating skills.

Examples of pathogens associated with food poisoning that were tested with the “DNA chip card”

Enterohemorrhagic Escherichia coli

Salmonella

Campylobacter

Vibrio parahaemolyticus

Shigella

Staphylococcus aureus

Enterotoxigenic Escherichia coli

Enteroaggregative Escherichia coli

Enteropathogenic Escherichia coli

Clostridium perfringens

Bacillus cereus

Yersinia

Listeria

Vibrio cholerae

I think 14 is the highest number of tests I’ve seen for one of these chips. This chip is quite an achievement.

One final bit from the news release about the DNA chip provides a brief description of the gateway and something they call King SkyFront,

About KING SKYFRONT

The Kawasaki INnovation Gateway (KING) SKYFRONT is the flagship science and technology innovation hub of Kawasaki City. KING SKYFRONT is a 40 hectare area located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International Airport (also often referred to as Haneda Airport).

KING SKYFRONT was launched in 2013 as a base for scholars, industrialists and government administrators to work together to devise real life solutions to global issues in the life sciences and environment.

I find this emphasis on the city interesting. It seems that cities are becoming increasingly important and active where science research and development are concerned. Europe seems to have adopted a biannual event wherein a city is declared a European City of Science in conjunction with the EuroScience Open Forum (ESOF) conferences. The first such city was Dublin in 2012 (I believe the Irish came up with the concept themselves) and was later adopted by Copenhagen for 2014. The latest city to embrace the banner will be Manchester in 2016.