Tag Archives: Sixiang Shi

Better bioimaging accuracy with direct radiolabeling of nanomaterials

Even I can tell the image is improved when the chelator is omitted,

Courtesy: Wiley

A Feb. 9, 2017 news item on phys.org describes a new, chelator-free technique for increased bioimaging accuracy,

Positron emission tomography (PET) plays a pivotal role for monitoring the distribution and accumulation of radiolabeled nanomaterials in living subjects. The radioactive metals are usually connected to the nanomaterial through an anchor, a so-called chelator, but this chemical binding can be omitted if nanographene is used, as American scientists report in the journal Angewandte Chemie. The replacement of chelator-based labeling by intrinsic labeling significantly enhances the bioimaging accuracy and reduces biases.

A Feb 9, 2017Wiley press release (also on EurekAlert), which originated the news item, provides more detail,

Nanoparticles are very promising substances for biodiagnostics (e.g., detecting cancerous tissue) and biotherapy (e.g., destroying tumors by molecular agents), because they are not as fast [sic] metabolized as normal pharmaceuticals and they particularly enrich [sic] in tumors through an effect called enhanced permeability and retention (EPR). Chelators, which have a macrocyclic structure, are used to anchor the radioactive element (e.g., copper-64) onto the nanoparticles’ surface. The tracers are then detected and localized in the body with the help of a positron emission tomography (PET) scanner. However, the use of a chelator can also be problematic, because it can detach from the nanoparticles or bias the imaging. Therefore, the group of Weibo Cai at University of Wisconsin-Madison, USA, sought for chelator-free solutions—and found it in nanographene, one of the most promising substances in nanotechnology.

Nanographene offers the electronic system to provide special binding electrons for some transition metal ions. “π bonds of nanographene are able to provide the additional electron to stably incorporate the 64Cu2+ acceptor ions onto the surface of graphene,” the authors wrote. Thus, it was possible to directly and stably attach the copper isotope to reduced graphene oxide nanomaterials stabilized by poly(ethylene glycol) (PEG), and this system was used for several bioimaging tests including the detection of tumors in mice.

After injection in the mouse model, the scientists observed long blood circulation and high tumor uptake. “Prolonged blood circulation of 64Cu-RGO-PEG […] induced a prompt and persistent tumor uptake via EPR effect,” they wrote. Moreover, the directly radiolabeled nanographene was readily prepared by simply mixing both components and heating them. This simple chelator-free, intrinsically labeled system may provide an attractive alternative to the chelator-based radiolabeling, which is still the “gold standard” in bioimaging.

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

Chelator-Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation by Sixiang Shi, Cheng Xu, Dr. Kai Yang, Shreya Goel, Hector F. Valdovinos, Dr. Haiming Luo, Emily B. Ehlerding, Dr. Christopher G. England, Dr. Liang Cheng, Dr. Feng Chen, Prof. Robert J. Nickles, Prof. Zhuang Liu, and Prof. Weibo Cai. Angewandte Chemie International Edition DOI: 10.1002/anie.201610649 Version of Record online: 7 FEB 2017

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Nanojuice in your gut

A July 7, 2014 news item on Azonano features a new technique that could help doctors better diagnose problems in the intestines (guts),

Located deep in the human gut, the small intestine is not easy to examine. X-rays, MRIs and ultrasound images provide snapshots but each suffers limitations. Help is on the way.

University at Buffalo [State University of New York] researchers are developing a new imaging technique involving nanoparticles suspended in liquid to form “nanojuice” that patients would drink. Upon reaching the small intestine, doctors would strike the nanoparticles with a harmless laser light, providing an unparalleled, non-invasive, real-time view of the organ.

A July 5, 2014 University of Buffalo news release (also on EurekAlert) by Cory Nealon, which originated the news item, describes some of the challenges associated with medical imaging of small intestines,

“Conventional imaging methods show the organ and blockages, but this method allows you to see how the small intestine operates in real time,” said corresponding author Jonathan Lovell, PhD, UB assistant professor of biomedical engineering. “Better imaging will improve our understanding of these diseases and allow doctors to more effectively care for people suffering from them.”

The average human small intestine is roughly 23 feet long and 1 inch thick. Sandwiched between the stomach and large intestine, it is where much of the digestion and absorption of food takes place. It is also where symptoms of irritable bowel syndrome, celiac disease, Crohn’s disease and other gastrointestinal illnesses occur.

To assess the organ, doctors typically require patients to drink a thick, chalky liquid called barium. Doctors then use X-rays, magnetic resonance imaging and ultrasounds to assess the organ, but these techniques are limited with respect to safety, accessibility and lack of adequate contrast, respectively.

Also, none are highly effective at providing real-time imaging of movement such as peristalsis, which is the contraction of muscles that propels food through the small intestine. Dysfunction of these movements may be linked to the previously mentioned illnesses, as well as side effects of thyroid disorders, diabetes and Parkinson’s disease.

The news release goes on to describe how the researchers manipulated dyes that are usually unsuitable for the purpose of imaging an organ in the body,

Lovell and a team of researchers worked with a family of dyes called naphthalcyanines. These small molecules absorb large portions of light in the near-infrared spectrum, which is the ideal range for biological contrast agents.

They are unsuitable for the human body, however, because they don’t disperse in liquid and they can be absorbed from the intestine into the blood stream.

To address these problems, the researchers formed nanoparticles called “nanonaps” that contain the colorful dye molecules and added the abilities to disperse in liquid and move safely through the intestine.

In laboratory experiments performed with mice, the researchers administered the nanojuice orally. They then used photoacoustic tomography (PAT), which is pulsed laser lights that generate pressure waves that, when measured, provide a real-time and more nuanced view of the small intestine.

The researchers plan to continue to refine the technique for human trials, and move into other areas of the gastrointestinal tract.

Here’s an image of the nanojuice in the guts of a mouse,

The combination of "nanojuice" and photoacoustic tomography illuminates the intestine of a mouse. (Credit: Jonathan Lovell)

The combination of “nanojuice” and photoacoustic tomography illuminates the intestine of a mouse. (Credit: Jonathan Lovell)

This is an international collaboration both from a research perspective and a funding perspective (from the news release),

Additional authors of the study come from UB’s Department of Chemical and Biological Engineering, Pohang University of Science and Technology in Korea, Roswell Park Cancer Institute in Buffalo, the University of Wisconsin-Madison, and McMaster University in Canada.

The research was supported by grants from the National Institutes of Health, the Department of Defense and the Korean Ministry of Science, ICT and Future Planning.

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

Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines by Yumiao Zhang, Mansik Jeon, Laurie J. Rich, Hao Hong, Jumin Geng, Yin Zhang, Sixiang Shi, Todd E. Barnhart, Paschalis Alexandridis, Jan D. Huizinga, Mukund Seshadri, Weibo Cai, Chulhong Kim, & Jonathan F. Lovell. Nature Nanotechnology (2014) doi:10.1038/nnano.2014.130 Published online 06 July 2014

This paper is behind a paywall.