SPECIAL REPORT
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The manipulation of matter at the molecular level, nanotechnology continues to be heralded as one of the most promising technologies for the field of healthcare. Whenever the topic comes up in medical circles, whispers follow about precisely targeted drug delivery systems and microscopic disease-detecting sentinels patrolling our internal organs. While nanotechnology has not yet delivered healthcare breakthroughs on that scale, extensive R&D efforts are putting researchers one step closer to turning possibilities into actualities. The bad news is that Europe may be falling behind in the race to apply that research to commercial products.
Because of the potentially lucrative nature of nanotechnology, countless companies are plunging into the industry pool and fighting to stay afloat. In fact, approximately 35% of medical-oriented nanotechnology companies worldwide have been established since 2000, reports Biomedical Market Newsletter Inc. (Costa Mesa, CA, USA). In this global race to bring nano-technology to the masses, however, Europe may be trailing the pack, according to some analysts.
Despite billions of euros in funding for nano-technology research and development, the technology is not transitioning easily from the lab to the marketplace. Significantly fewer patents for the commercialization of nanotechnology have been filed in Europe than in the United States and the Far East, according to a report released by patent and trademark law firm Marks & Clerk (London).
“Whilst it is good to see significant public investment in Europe, the low number of patents filed shown by our report gives serious cause for concern,” says Rhian Granleese, partner at the firm and coauthor of the study. “Some estimates predict that the value of the nanotechnology products and services market will exceed >1 trillion by 2015, but European institutions and companies may be forgoing their claim to commercial returns by not filing patents on their research.”
The European Science Foundation (ESF) also has acknowledged Europe’s difficulty gaining a footing in the marketplace. “European scientists often lack the ability to harness the entrepreneurial, commercially driven research necessary to enable rapid exploitation,” the ESF states in its policy briefing titled Scientific Forward Look on Nanomedicine. “To win and maintain a leading position in nanomedicine, it is essential that Europe improve technology transfer and shorten timelines from research to market.” To achieve this objective, the organization stresses the importance of establishing a programme in support of commercial and academic ventures. Notably, ESF recommends instituting more GMP manufacturing sites to expedite projects by small and medium-sized businesses to the clinical development phase.
Fostering cross-disciplinary collaborations in nanotechnology and nanomedicine is also key to creating a sustainable industrial programme. Experts and policymakers alike agree that in order to make progress in nanomedicine, researchers from all fields, including chemistry, biomedicine, and even electronics, must come together, communicate, and share ideas.
Making It Stick
While nanotechnology undoubtedly will change the face of modern medicine, there are relatively few actual applications on the market just yet. One that has recently emerged involves the use of nanocoatings to stem nosocomial infections. Hospital related infections are on the rise. In Germany alone, an estimated 600,000 patients acquire nosocomial infections each year, according to Michael Wagener, managing director of sales for Bio-Gate AG (Bremen, Germany). In an effort to curb this problem, Bio-Gate and several other companies are turning to nanotechnology for answers.
Coating implantable devices and medical instruments with silver nanoparticles keeps bacteria at bay due to the element’s antimicrobial properties. The particles are effective at inhibiting the formation of biofilms on coated catheters or implants. “By using very small particles with a huge surface area, the concentration of the antimicrobial agent can be kept very low in comparison with other organic antimicrobial agents,” Wagener says.
Silver-based nanocoatings are used in many applications worldwide, notably in wound dressings and bandages. Researchers are also exploring the option of coating hospital garments with silver-based formulas to prevent the spread of infection among patients.
Nanotechnology-based coatings in general are the focus of extensive R&D throughout Europe. One collaborative effort involving researchers in five countries is exploring the adhesive property that causes cells to stick to other surfaces and determining whether it can be applied to the production of a new generation of biomaterial coatings. Sponsored by the European Union, this project is seeking ways to prevent or promote cell-to-surface adhesion.
Precise, Targeted Drug Delivery
ESF counts colloid and polymer chemistry for drug-delivery applications among its strengths in R&D. And that’s a good thing from a commercial perspective: drug delivery is considered to be one of the fastest-growing sectors of nanotechnology. Research from analysts at the US-based NanoMarkets firm reveals that the global drug-delivery products and services market is forecast to surpass €50 billion by 2009. Nanotechnology-based drug-delivery systems, according to the report, would account for more than €1.3 billion that same year.
Nano-based drug-delivery systems could have a profound impact on the treatment of scores of diseases. Researchers believe that nanocarriers could enable targeted, controlled release of therapeutic agents to treat cancer, for example. The future of drugs and their delivery will evolve from “formulations based on polymer conjugates and liposomes as carriers of drugs” to nanoparticles linked to antibodies or proteins that specifically target diseased tissue, according to Professor Alberto Gabizon of Shaare Zedek Medical Centre and Hebrew University (Jerusalem, Israel). Eventually, nanoparticles will consist of an amalgam of nanomaterials, imaging agents, antibodies, and controlled systems, he says.
A project spearheaded by Cardiff University has a team of British researchers exploring the use of nanomedicine for targeted drug delivery. Deploying a drug-delivery agent into the body is a tricky business, since the body’s immune system is trained to ward off foreign invaders. The key, according to Peter Griffiths, PhD, a researcher and professor at Cardiff’s School of Chemistry, is to build a vehicle that is small enough to travel through the body undetected.
“We are aiming to create a polymer—a long molecule—to act as a shield for the drug, protecting it from the body’s defenses,” says Griffiths. The researchers aim to “guide the molecule into the target cell, and then have it dissolve away safely while the drug dose does its work.” Potential applications for the drug-delivery method include the treatment of cancer, eye disease, and arthritis.
Sensing a Problem
An ounce of prevention is worth a pound of cure, as the saying goes, and while drug-delivery methods may permit healthcare professionals to directly combat cancer, the prospect of an early warning system to detect the formation of a tumour in its earliest stages may be even more exciting.
The Optonanogen project, which is part of the European Commission’s Information Society Technologies (IST), has yielded the creation of a portable biosensor microsystem that detects mutations of a particular gene that is sometimes responsible for breast cancer in women.
Later iterations of the system may enable it to detect anomalies on almost any gene. As a result, medical professionals would be able to warn patients of genetic hazards. The device could produce test results revealing a patient’s predisposition to a disease in just minutes, as compared with hours or days using traditional lab tests.
Roughly the size of a human hand, the microsystem will consist of an array of microcantilevers, an optical detection system, and a polymer microfluidic system. “The hybrid integration of the proposed DNA biochip, in which the array, detector, and fluid transport are miniaturized and integrated into a single unit, will be the first attempt in the integration of a nanobiodevice,” according to IST.
IST further explores nanotechnology’s role in biosensing through its Future and Emerging Technologies initiative. A joint effort by French, Italian, and Spanish researchers, the Spot-Nosed project developed an olfactory nanobiosensor array that mimics the way in which human and animal noses respond to different odours.
Consisting of nanobiotransducers, each with a single olfactory receptor attached onto a metal nanoelectrode, the biosensor replicates the reaction that occurs in animals’ noses when proteins that make up olfactory receptors come in contact with the different odorants. Often, these smells are not detectable by humans.
The researchers plan on extending their research beyond its original scope and equipping the electric nose with the ability to actually recognize smells. If successful, the project’s findings could result in applications that diagnose organ failure, bacterial infections, and terminal diseases, according to Josep Samitier, coordinator of the project.
Keeping It Safe
Largely because of the minute size of the particles and the sometimes surprising properties that the materials display at the molecular level, nanotechnology also raises concern in some quarters. Recognizing that there is legitimate cause to investigate, the European Union funded safety analyses. The Nanotox initiative examines how nanoparticles disperse and their potential side effects in patients. Nanotechnology’s impact on manufacturing and the development of safety standards are also under study. The programme will launch an online European database that links to relevant sites regarding research, policy, and ethics. Moreover, Nanotox will establish guidelines for legislators, regulators, and policymakers based on its assessment of ethics, policies, and codes of practice.
Through the European Commission, other initiatives have been launched to assess the safety of nanoparticles and to further develop testing guidelines. Worker safety in relation to nanoparticles and other nanotechnology-based research is also the subject of investigation.
Nanotechnology boosters found some comfort in a study conducted at the School of Pharmacy at the University of London. Researchers reportedly determined that modified carbon nanotubes—often considered the Holy Grail of nanotechnology—do not have toxic side effects after intravenous injection into the body.
Prior to injecting them into the body, researchers modified the surfaces of the carbon nanotubes to make them more compatible with the body. After entering the body, the nanotubes were detected in the organs but were eliminated and excreted in urine soon after. The researchers involved in the study championed the potential that the nontoxic carbon nanotubes hold for the future of medicine, especially in terms of drug delivery systems.
“We hope that our results will provide help in the search for a new generation of safe and effective medical therapies,” says Kostas Kostarelos, lead author of the study. “The next stage of our work will be to investigate ways of controlling the length of time that these nanotubes remain in the body, to allow them to carry out their work before they are excreted.”
The Future
Pan-European and national bodies have invested significant resources in the exploration of nanotechnology and its potential applications in the healthcare sector. In addition to developing new coatings, drug-delivery methods, and biosensors, Europe is pioneering research in such fields as imaging and tissue regeneration. But the scientific community needs the support of entrepreneurs and forward-thinking public bodies to bring the promise of nanotechnology to the marketplace. There is still room at the bottom, to paraphrase physicist and nanotechnology pioneer Richard Feynman, but hurry: the spaces are filling fast.
