Behind the buzz and beyond the hype:
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Posted: May 7th, 2007
The potential and the pitfalls of nanomedicine
(Nanowerk Spotlight) For centuries, man has searched for miracle cures to end suffering caused by disease and injury. Many researchers believe nanotechnology may be mankind’s first “giant step” toward this goal. Whether these beliefs are based on facts or hope, many corporations and governments are willing to invest a great deal of money to find out what happens when nanotechnology is used for medical applications – the emerging field of nanomedicine. Hundreds of millions, if not billions of dollars have been invested by governments, such as the U.S. National Cancer Institute, and the private sector in nanomedicine research and nanotech-related life sciences ventures. The 2008 budget of the U.S. National Nanotechnology Initiative provides more than $200 million for the National Institutes of Health. The European Union, particularly Germany and the UK, and Japan are also investing heavily in this field. It is difficult to find fault with a technology that promises to cure cancer almost before it starts and prevent the spread of AIDS and other infectious diseases. Scientists around the globe are searching for ways to exploit nanoparticles to improve human health. However, there are toxicological concerns and ethical issues that come with nanomedicine and they have to be addressed alongside the benefits.
The medical advances that may be possible through nanotechnology range from diagnostic to therapeutic, and everything in between.
In the past few decades, imaging has become a critical tool in the diagnosis of disease. The advances in the form of magnetic resonance and computer tomography are remarkable, but nanotechnology promises sensitive and extremely accurate tools for in vitro and in vivo diagnostics far beyond the reach of today’s state-of-the-art equipment.
As with any advance in diagnostics, the ultimate goal is to enable physicians to identify a disease as early as possible. Nanotechnology is expected to make diagnosis possible at the cellular and even the sub-cellular level.
Quantum dots in particular have finally taken the step from pure demonstration experiments to real applications in imaging. In recent years, scientists have discovered that these nanocrystals can enable researchers to study cell processes at the level of a single molecule. This may significantly improve the diagnosis and treatment of cancers. Fluorescent semiconductor quantum dots are proving to be extremely beneficial for medical applications, such as high-resolution cellular imaging. While quantum dots could revolutionize medicine, unfortunately, most are toxic. However, recent studies conducted at the University of California, Berkeley, have shown that protective coatings for quantum dots may eliminate toxicity.
In terms of therapy, the most significant impact of nanomedicine is expected to be realized in drug delivery and regenerative medicine. Nanoparticles enable physicians to target drugs at the source of the disease, which increases efficiency and minimizes side effects. They also offer new possibilities for the controlled release of therapeutic substances. Nanoparticles are also used to stimulate the body’s innate repair mechanisms. A major focus of this research is artificial activation and control of adult stem cells.
Peptide amphiphiles that support cell growth to treat spinal cord injury; magnetic nanoparticles and enzyme-sensitive nanoparticle coatings that target brain tumors; smart nanoparticle probes for intracellular drug delivery and gene expression imaging, and quantum dots that detect and quantify human breast cancer biomarkers are just a few of the advances researchers have already made.
Interestingly enough, there could be massive shifts in economic value among pharmaceutical companies. While the new nanomedicines open up enormous market and profit potentials, entire classes of existing pharmaceuticals such as chemotherapy agents worth billions of dollars in annual revenue would be displaced.
Nanomedicine, and nanotechnology in general, is new and little experimental data about unintended and adverse effects exists. The lack of knowledge about how nanoparticles might affect or interfere with the biochemical pathways and processes of the human body is particularly troublesome. Scientists are primarily concerned with toxicity, characterization and exposure pathways.
A recent article (pdf download, 34 KB) in the Medical Journal of Australia states that safety regulation of nanotherapeutics may present unique risk assessment challenges, given the novelty and variety of products, high mobility and reactivity of engineered nanoparticles, and blurring of the diagnostic and therapeutic classifications of “medicines” and “medical devices.”
Despite these concerns, 130 nanotech-based drugs and delivery systems and 125 devices or diagnostic tests have entered pre-clinical, clinical, or commercial development since 2005, according to NanoBiotech News.
Currently, in the U.S., the NIH is evaluating several safety issues, including particle pathways in the human body; the length of time nanoparticles remain in the body; the effects on cellular and tissue functions; access to systemic circulation through dermal exposure; and unanticipated reactions in vivo. The National Cancer Institute’s Nanotechnology Characterization Laboratory is working to develop standards for advancing the new class of molecular-sized cancer drugs through clinical trials.
The issue of safety is a global concern. In Europe, the SCENIHR Report (pdf download, 234 KB) and the white paper Nanotechnology Risk Governance (pdf download, 1.2 MB) published in June 2006 by the International Risk Governance Council address the issue. Both reports emphasize the lack of data on potential risks associated with nanomedicine and nanotechnology with regard to the human-health and ecological consequences of nanoparticles accumulating in the environment.
One of the world’s leading experts in nanotoxicology is Günter Oberdörster, professor of Toxicology in Environmental Medicine at University of Rochester. "There is a lot of hype surrounding the promises of nanomedicine. Indeed many things look very promising, but until now there are only animal studies to show a proof of principle," Oberdörster told Nanowerk.
Although he is concerned about safety issues related to nanomedicine, Oberdörster said he has faith in the regulatory process: “I am confident that the FDA will require the appropriate toxicity testing before approving any nanomedicine applications.”
But, he cautioned, that testing must be comprehensive. "If toxicity testing is only done in healthy organisms (animal data or controlled clinical studies), adverse effects may still occur in susceptible parts of the population which would require more specific testing," he said, adding that he is far more concerned with nanoparticle applications outside the medical field.
Other than the obvious potential risks to patients, there are other toxicological risks associated with nanomedicine. Concerns over the disposal of nanowaste and environmental contamination from the manufacture of nanomedical devices and materials are valid. “These are potential risks which need to be carefully assessed,” said Oberdörster. “This has not been done yet.”
Beyond the issue of safety lies the question of society’s ethical use of nanotechnology. According to Professor John Weckert of the Centre for Applied Philosophy and Public Ethics, there have been numerous questions raised concerning the ethical use of nanomedicine.
Informed consent, risk assessment, toxicity and human enhancement are just a few of the ethical concerns voiced in this passionate debate. Weckert, who was recently named editor-in-chief of a new peer-reviewed journal called NanoEthics: Ethics for Technologies that Converge at the Nanoscale, believes the discussion of ethics and nanomedicine will bring many more difficult questions for global society. "Genetic testing, for example, might become much easier and more widely available," he explains. "The issue of aborting defective fetuses will become one that more people will have to face," says Weckert.
In fact, nanomedicine will raise many societal questions. According to the European Commission’s Group on Ethics in Science and New Technologies (EGE) the question of informed consent where nanomedicine is involved is complicated. "Consent may not be too difficult to obtain, but when is it informed? And when is it free?" asks the EGE in an opinion paper released in January (The Ethical aspects of Nanomedicine; pdf download, 1.5 MB).
"Informed consent requires the information to be understood. How is it possible to give information about future research possibilities in a rapidly developing research area and to make a realistic risk assessment in view of the many unknowns and the complexities?"
According to the EGE, due to knowledge gaps and the complexity of the matter, it may be difficult to provide adequate information concerning a proposed diagnosis, prevention and therapy needed for informed consent.
Another issue is the fine line between medical and non-medical uses of nanotechnology for diagnostic, therapeutic and preventive purposes. The question of whether nanotechnology should be used to make intentional changes in or to the body when the change is not medically necessary is yet another hot topic in the long list of concerns.
The good news is that these questions are being asked, but there is still much work to be done. According to Weckert, the European Union has taken the lead in raising the question of ethics and nanomedicine. "In the EU, there seems to be more concern about potential problems and therefore more discussion prior to the technology being developed," said Weckert. "The Europeans in general are more sympathetic to the precautionary principle than is the case in the U.S."
Despite the enormous promise of nanomedicine, and the considerable funding going into the field, the research into the ethical, legal and social implications of nanomedicine is comparatively minute. As Peter Singer wrote in his 2003 tutorial "Mind the gap: science and ethics in Nanotechnology": “The science leaps ahead, the ethics lags behind.” As with nanotechnology in general, there is danger of derailing nanomedicine if the study of ethical, legal and social implications does not catch up with scientific developments.