BERLIN – If NanoMed 2009 began with a futuristic look to the broad potential for nanoparticles as building blocks for medical procedures and therapies (see accompanying story), it closed with a more applied view of devices in development (see MDD, Nov. 26, 2008).

Hans Hofstraat, vice president at Philips Research (Eindhoven, the Netherlands), described two programs using magnetically responsive nanoparticles for the detection and diagnosis of cardiovascular disease.

Closest to a clinical application is a point of care (PoC) diagnostic assay being developed using Philip's Magnetic Particle Biosensor Technology.

The MAGNOtech platform uses magnetic nano particles preloaded into the assay card that are coated appropriate ligand molecules formulated for the specific molecules targeted for the diagnosis of a fluid sample from a patient.

The sample is sandwiched on the flat lab-on-chip card and introduced to a hand-held reader.

A magnetic pulse draws all molecules in the sample against the lower layer of the sandwich where targeted molecules bind with the agent formulated for their capture. A second pulse from the top side of the assay card pulls away the non-bound particles, washing the sample.

A laser flashes the active bottom layer and an optic reader measures remaining target molecules assesses the density of targeted molecules in the sample.

The four-minute test utilizes the same optic-laser system found in a common DVD player, lowering the costs and enhancing the portability of the device. The assay card, constructed entirely from plastic components, has no moving parts or embedded electronics and is disposable.

Philips recently applied this technology to a hand-held device for a roadside test for drugs of abuse with Concateno (Oxfordshire, UK) and promised an announcement of a medical application in1Q09 (MDD, Nov. 25, 2008).

At that time Jos Rijntjes, general manager for point-of-care cardiac testing with Philips in Eindhoven, told Medical Device Daily a DVD player "actually is a source for beautiful, and cheap, optics" giving the device a capability to scan the surface of the card and see only the particles that bind.

He explained the magnetic force moves the identified molecules through the solution 100 times faster than using a natural diffusion model, increasing the speed to results.

Hofstraat said "Forensics is a small, niche market but the advantage of an early roll out with a partner for a non-regulated application in drugs of abuse is to give us experience in the field use of this device," he said, adding that when the assay is ready for the clinic, the hand-held reader will be as well.

Another novel Philips development using nanoparticles made from ferrous oxide, commonly known as rust, is being hailed as a breakthrough in cardiovascular diagnosis.

Magnetic Particle Imaging (MPI) made its scientific début the first of March when results from a pre-clinical study conducted at Mount Sinai Heart Center (New York) were published in Physics in Medicine and Biology.

"MPI offers the specificity of SPECT (single photon emission computed tomography) without the radiation and it renders three-dimensional, real-time in vivo images," Hofstraat told MDD in an interview at NanoMed.

Valentin Fuster, MD, PhD, who led the study at Mount Sinai, said Philips' MPI showed "great potential to characterize the disease processes associated with atherosclerosis, in particular those associated with vulnerable plaque formation, which is a major risk factor for stroke and heart attacks."

Hofstraat said the prototype MPI was invented and built at Philips' research center in Hamburg and has so far been used on rodents.

The center has constructed an imitation of a human coronary artery currently being used for further proof-of-concept testing.

The procedure calls for injecting the iron-oxide-based MRI contrast agent Resovist from Bayer Schering Pharma (Berlin), which are nanoparticles measuring approximately 30µ, into the patient's bloodstream (MDD, Jan. 16, 2009).

The particles appear as bright signals to the MPI as they flow in the bloodstream.

The MPI is a scanner like conventional magnetic resonance imaging (MRI) that renders sliced images of the patient and the iron oxide introduced into the body is similar in principle to the contrast agents used for highlighting tissue characteristics during an MRI scan.

But where MRI registers and then renders an image of the magnetic response of the tissues, the MPI enables direct imaging of magnetic nanoparticles themselves, with significant benefits for functional cardiovascular diagnosis.

MPI offers high spatial resolution with short image acquisition times as opposed to the indirect inversion caused by MRI relaxometry that results in a poorer quality spatial resolution.

The MPI allows a cardiologist to see in real time the dynamic concentration changes as the nanoparticles are swept along, enabling measurements of coronary blood supply, myocardial perfusion, and ejection fraction from the heart, as well as wall motion and flow speeds.

"This is revolutionary," said Hofstraat, "It combines high sensitivity, high resolutions and fast acquisition for visualizing functional parameters."

"When combined with other imaging modalities that render the patient's anatomy and other morphology, the cardiologists will be looking at a full depiction of a specific patient's condition in a way that has never been shown before," he said.

The Hamburg-built prototype is not yet ready for prime time, he cautions. "This is still research," he said, estimating that a clinical application for a fully operational human-scale system may be from seven to 10 years away.

While his keynote address focused on magnetic particles, Hofstraat also reviewed for the group the development effort being led by Philips to use nanoparticles for drug delivery (MDD, Jan. 8/Jan. 22, 2009).

Last month Philips announced it is leading a consortium of 15 companies in the SonoDrug program focused on the development of therapeutics transported by nanoparticles to a targeted site in the body where a focused beam of ultrasound then releases the drug (MDD, Feb. 2, 2009).

Funded with €11 million ($14 million) from the European Union's Framework 7 program, the SonoDrug partners will contribute a third of the financing for the four-year program, totaling €5 million ($6.5 million) as well as expertise and in-kind services for research and prototype development.

In the interview with MDD, Hofstraat explained the therapeutics encapsulated in the nano particles are either too toxic to be introduced to the body systemically, or else are nonsoluble, or may be too fragile to resist the body's internal defenses.

The goal, he said, is to release the therapeutic at the targeted site to minimize side effects and maximize the effectiveness of treatment

The SonoDrug actuation device is a combination ultrasound unit being built at Philips research center in Briarcliff Manor, New York that uses conventional ultrasound signals to monitor the delivery of the particles to a selected site, such as a tumor, along with a high frequency ultrasound (HIFU) transducer to trigger the release.

The power range of the HIFU needs to be calibrated to burst the capsules, he said, without burning the body's tissue. n

(MDD Nanotechnology R&D Report 2009 reports on activity in the nanotechnology sector. For more information, call 800-688-2421 or 404-262-5476.)

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