BERLIN – Move over, microsurgeons. Make a little space for nanosurgery.

While we are making this paradigm shift change, let's also get rid of the operating table, the overhead lights and those trays of surgical instruments.

But keep the diagnostic equipment warmed up, and update the software to handle megabytes of real-time molecular imaging.

If mini-minimally invasive microsurgery was the crowning achievement of the last century, nanotechnology is blazing a new trail for diagnosis, therapy and surgical-like interventions for this century.

In his keynote address opening the 6th International Conference on Biomedical Applications of Nanotechnology here, Paras Prasad, PhD, of the University of Buffalo (Buffalo, New York), painted a sweeping vision of how microscopic particles mixing chemical, electro-magnetic and biological properties are poised to reinvent not only how we see and then treat disease but to transform as well our understanding of what disease actually is in the first place.

Held in an aging medical lecture hall of the venerable Charité Hospital, NanoMed 2009, the blessedly shortened version in popular use here, gathered leading researchers from around the world as well as leading medical doctors recognizable from presentations at cardiology and radiology conferences in Europe over the past year.

Convened on an as-needed basis, this sixth meeting since the series began in 1999 is built around 30 accepted abstracts and 40 poster presentations that at first glance would seem to be the stuff of biotechnology with a near-toxic overload of chemistry, biology, genetics and metabolic processes.

Yet a closer look reveals telling language that speaks to the paradigm shift ahead for interventions that are not systemic formulations but surgical actions more precise, and possibly more effective, than surgery itself.

In his presentation, "Transforming Nanotechnology into Solutions for 21st Century Healthcare Challenges," Prasad showed how nanoparticles are increasingly engineered as multifunctional platforms capable of detecting a disease state and treating it selectively as the physician monitors in real time the effects on cellular and even molecular levels.

Quantum dot probes, nanomagnetic ablation, and "bad" gene silencing identical to the effects of dissecting a bad organ, suggest corollaries in conventional surgery.

"Isaac Asimov told us about the Fantastic Voyage, but he described a submarine," Prasad told Medical Device Daily following his speech.

"I would agree you could accurately call what we are doing nanorobotics. The effect is much the same as the kind of intervention Asimov imagined but with multifunctional nano-platforms performing the work," he said.

At the end of the day, literally, the great challenge ahead for nanosurgery is similar to the problem faced by the crew of Asimov's submarine, Proteus: doing the work and then getting out safely.

Or to put it in common medical terms, "Where do these nanoparticles actually go?"

Do they end up in the liver and stay there? Are they excreted? If they are excreted, are they a toxic substance introduced into the environment? Can they be designed to biodegrade? (See MDD, Feb. 13, 2009: "Battle is brewing in Europe over regulation of nanotech.")

Agn s Pottier, head of nanochemistry for NanoBiotix (Paris), told MDD, "This is exactly where we are working now, to be able to clearly know what happens to the particles."

Pottier's work is at the sharp edge of development at NanoBiotix, which is pointed to a milestone first-in-man (FIM) clinical study for its NanoXray product in 2010.

She said to her knowledge NanoBiotix is the only company so close to clinical trials with the concept of what she called "on-off activation of a nanoparticle."

Pottier was quick to distance the NanoXray project from the multimodality platforms described by Prasad in his keynote address saying the current product is a relatively, externally activated device, which is very different from the complex functionalities possible in the future for nano-interventions, she said.

The nanoparticle developed by Nanobiotix is a non-drug agent with an inert and inactive substance called Nbtxr3 that is coated with a material taken up by cancerous cells (MDD, May 7, 2008).

The particles accumulate at a tumor site and can be activated with exposure to common X-ray radiation resulting in tumor necrosis by inducing a chain reaction where a reactive oxygen intermediate blocks the formation of free radicals and arrests the cytotoxic response of tumor cells.

Nearby healthy tissue is not affected and Nanobiotix believes this therapy will revolutionize conventional radiotherapy where an estimated 50% to 60% of all cancer patients are treated at some point with a stream of high-energy gamma rays.

Pottier said the FIM studies for NanoXray will be conducted in France where the particle has been classed as a medical device, and not a therapeutic, by the French regulatory authority, Agence Fran aise de Sécurité Sanitaire des Produits de Santé (AFSSAPS).

Nanobiotix's founder/CEO, Laurent Levy, worked on the discovery and early development of the nanoparticles during post-doctoral studies at what was then known as the State University of New York (SUNY) at Buffalo and licensed the technology from the Institute for Lasers, Photonics and Biophotonics that is directed by Prasad.

Nanobiotix last year was issued patents protecting its development of the NanoXray technologies (MDD, Oct 16, 2008).

"Our technology has been taken a very long way with Nanobiotix," Prasad said with unabashed pride at the podium.

NanoXray is the company's lead project and main focus but the growing expertise in nanomedicine and developing nanoparticle platforms has expanded the scope of the company's interests.

Last year Nanobiotix announced a collaboration with Malaysian Biotechnology (BiotechCorp; Kuala Lumpur, Malaysia) to develop point-of-care (POC) diagnostics and drug delivery systems for tropical diseases, such as malaria (MDD, Sept. 25, 2008 and Oct. 3, 2008).

And last month the company joined a European consortium called SonoDrugs funded by the European Union and led by Royal Philips Electronics (Eindhoven, the Netherlands) to develop local drug delivery using nanoparticles activated by ultrasound. (MDD, Feb. 2, 2009) (See accompanying story, page 1).

In his keynote describing a future for nanotechnology, Prasad moved quickly for a mostly post-doctoral audience outlining the diverse characteristics of the new nanoplatforms that can be engineered, including chemical make up, shape, size, porosity, surface charge, surface characteristics (hydrophilic or hydrophobic) and surface coatings (organic, protein or nucleic acid).

They can be applied in procedures that are in vitro, ex vivo and in vivo, he said.

Prasad showed an example of a nano-imitation of a cell using microbeads that can be introduced into the metabolism coated with antibodies to extract soluble proteins, much like endoscopic aspiration is used today to extract sample tissue.

A nanoparticle might instead be charged with a payload to deliver receptor-specific therapeutics, with the same intent that surgeons today using macro-scale tissue effects and induced necrosis with radiofrequency ablation or cryotherapy.

More intriguingly is a potential in the 21st Century for gene therapies using nanoparticles.

For diseases caused by a failure of gene expression, such as Alzheimer's, Parkinson's disease and cystic fibrosis, Prasad said, nanoparticles can reactivate and rejuvenate gene expression at the specific site of the disease.

In neurogenics he cited research showing the "bad" gene that drives morphine addiction can be "silenced," suggesting an application for nano-delivery.

Challenges to be solved for nanoparticles include breaking through the body's complex defense mechanisms, a problem memorably depicted by aggressive antibodies clinging to Proteus crew member Raquel Welch in Fantastic Voyage.

Crossing these barriers opens new potentials for directly interacting with proteomic and genetic cell structures with controlled delivery of therapeutics.

Other benefits of nanotechnology in diagnosis include multiplexing for disease detection with increased sensitivity and specificity.

"It will not be enough to say the patient has a flu but what kind of flu, or what specific leukemia across all the possible expressions," Prasad said, in order to provide an equally specific and therefore effective therapy. (MDD, Jan. 16, 2009.)

The four-day NanoMed event is divided into sessions on Nanotechnology in Cancer Treatment, Drug Delivery and Controlled Release, Nano Biomaterials and Regenerative Medicine, Nano Bioanalytics and Diagnostic Tools, and Nanomaterials in Dentistry.

In a concluding note, Prasad acknowledged the thin line that nanomaterials, and nanoparticles particularly, walk between pharmaceuticals and medical devices.

Fastest to market, he said, will be products such as NanoXray that are able to convince regulatory authorities the nanoparticle is used as a carrier and are excreted after the therapeutic effect is delivered.

"But if the FDA takes the nanoparticle to be a new drug formulation, then you are back on the pharma track to approval," he said.

The fastest to market of all applications, he said, will be nano beauty aids, particles with properties for deep skin penetration and intradermal delivery that are able to cross skin barriers to stop expression of "bad" genes that may be breaking down collagen, for example.

"Nanocosmetics play in a market that has gone from $19 billion in 2001 to $58 billion in 2008," he said.

These products fall under a completely different set of rules at the FDA as beauty aids and "bypass a lot of things to get to customers," he said.

No Comments