Alireza Mehdizadeh

ShERI-DB

Mehdizadeh on 02/18/2009 at 6:45am (UTC)

	The Fundus image database is now ready to release onsite. I hope this will be available on this site for testing from Feb 22nd 2009.

Ultrasmall nanoparticles pin-point cancer

Jul 2, 2008 on 07/08/2008 at 4:49am (UTC)

Functionalized magnetic nanoparticles have attracted considerable interest as disease-specific MRI contrast agents. However, the value of such agents is highly dependent on their size. Overly large particles face problems navigating through fine capillaries and reaching target cells outside blood vessels. They are also at greater risk of being trapped by the body's reticuloendothelial system.

But if the particles are too small, their signal may not be strong enough to make any difference to observable MR contrast. Very small nanoparticles may additionally be excreted before reaching their intended target.

US researchers have now created what they believe are the smallest, functionalized iron oxide nanoparticles to date that are suitable for targeted MRI (J. Am. Chem. Soc. 130 7542). Previously reported polymer-coated iron oxide nanoparticles have typically exceeded 30 nm in diameter, said co-author Shouheng Sun, professor of chemistry at Brown University (Providence, RI). This latest work, the result of collaboration between researchers from Brown and Stanford Universities, has reduced the overall particle size to less than 10 nm - small enough to improve efficacy, but not so tiny that the nanoparticles would be ejected almost immediately from the bloodstream.

"Particles with a diameter less than 7 nm will be removed from circulation very quickly by renal clearance after intravenous administration," Sun said. "We don't want to go below this limit if we want the particles to stay in the circulation long enough to target the desired sites."

The overall size of the nanoparticles is not the only important factor. The ratio between the magnetic core and the polymer shell is critical too. Iron oxide cores need to be sufficiently large and their coatings sufficiently thin for any signal change to be detectable. But if the balance is not quite right and the coating is too thin then the magnetic nanoparticles may simply clump together, making them more likely to be identified as "invaders".

Fine balance
The investigators first synthesized magnetic Fe3O4 nanoparticles with a core size of 4.5 nm and a coating layer of 4-methylcatechol (4-MC) ligands. This was achieved through thermal decomposition of iron pentacarbonyl (Fe(CO)5) in the presence of benzyl ether and 4-MC, followed by air oxidation. The 4-MC surface ligands were then linked directly to a specific peptide, c(RGDyK), via the Mannich reaction, giving the particles a ~2 nm-thick coating.

"4-methylcatechol has never been used before for iron oxide nanoparticle synthesis," Sun told medicalphysicsweb. "The good thing is that with this 4-MC coating, the nanoparticles can be coupled easily to species that terminate with an amine (NH2) group. Both the particle synthesis and the peptide conjugation steps are simple and straightforward."

The peptide-coated particles were stable for several months without precipitation in aqueous dispersion. Dynamic light scattering revealed the overall diameter to be 8.4±1.0 nm. The number of peptide molecules per particle was estimated to be between 100 and 200.
Cancer detection
Cancer detection

The specificity of the coated particles was demonstrated in vitro on two different types of human cancer cells. Iron uptake, taken as a measure of particle accumulation, was approximately five times higher for human glioblastoma cells (U87MG) than for human breast cancer cells (MCF-7).

MR images of mice bearing U87MG tumours and subsequent histology confirmed the ability of the functionalized particles to seek out and bind to target cells. Sites of nanoparticle accumulation could be identified on MRI from changes to signal intensity.

Although iron oxide nanoparticles are considered to be biocompatible, more detailed studies will be needed to confirm that these particular ultrasmall particles are not toxic, Sun said. "During the in vitro test, we did not observe these particles affecting cell viability. However, toxicity is an important and complex issue, especially at the in vivo level," he said.

Additional development work will also be conducted before the nanoparticles are considered for clinical trials. "We want to improve our system by conjugating other kinds of biovectors, apart from the c(RGDyK) peptide, onto the particles, to give them different kinds of targetability," Sun said. "We also plan to attach anti-cancer drugs onto our particles."

Magnetic particles seek out artery plaques

Jul 7, 2008 on 07/08/2008 at 4:42am (UTC)

Researchers in Taiwan have used magnetic nanoparticles to detect and label atherosclerotic plaques in rabbits. The technique, used in conjunction with MRI, will hopefully be extended for use in humans (Appl. Phys. Lett. 92 142504)
Atherosclerotic plaques form from a build up of cholesterol, inflammatory cells and fibrous tissue inside arteries. Some of these plaques, known as vulnerable atherosclerotic plaques (VAPs), easily break up to form blood clots that may then block blood flow to the heart or brain, potentially causing a heart attack or stroke.

Stained aorta
Several imaging techniques are used today to detect these plaques, including angiography, intravascular ultrasound, angioscopy and optical coherence tomography. However, these methods have some limitations when it comes to identifying high-risk coronary artery plaques.
Now, Hong-Chang Yang of the National Taiwan University and colleagues have developed a new technique that employs dextran-coated iron oxide nanoparticles around 45 nm across, biofunctionalized with anti-vascular cell molecule-1 (VCAM-1). These molecules are selectively expressed by arterial walls prone to VAP formation and act as an indicator for the plaques.
Aortic wall darkening
The researchers tested their technique by injecting rabbits that had hypercholesteremia – that is, the animals had soft plaques (assumed to be rich in VCAM-1 molecules) on arterial vessel walls. A day later, MRI examinations were performed on the rabbits. These showed aortic wall darkening (see figure). The animals were then killed and their aortic walls examined using dye stains.
MR images
"The regions that became stained mirrored the aortic darkening seen in the MRI scans," Yang told our sister site nanotechweb.org. "This implies that the aortic walls were anchored with anti-VCAM-1 functionalized magnetic nanoparticles as a marker of increased VCAM-1 expression."
"In addition to demonstrating the feasibility of in vivo artery plaque labelling using VCAM-1 biofunctionalized magnetic nanoparticles in animals, we look forward to using this technique for diagnosing other diseases in animals, and even human beings," added Yang.

SheERI-DB

Mehdizadeh on 07/07/2008 at 7:53am (UTC)

	Shiraz eye and Retinal Image-data Base(ShERI-DB)would be available soon for all researcher on this site thanks to my sincere friend Eng Shahram Mohammadi(Technical mannager and head of medical engineering office of Khodadoust eye hospital in Shiraz). you could find the Db on ShERI-DB page if this site.

<-Back

Continue->