Review Article

Nanomedicine: Research and Practice

Dr. Vijay K. Varadan,
Vijay K. Varadan1,2, Linfeng Chen1, Jining Xie1
1Department of Electrical Engineering, University of Arkansas, Fayetteville, Arkansas 72701
2Department of Engineering Science and Neurosurgery, Pennsylvania State University, University Park, PA 16801

Nanomedicine is generally defined as the medical applications of nanotechnology. Nanomedicine consists of five primary branches, including nanodiagnosis, nanopharmaceutics, implantable nanomaterials, implantable nanodevices, and nanosurgery. Before nanome

*Corresponding author:

Dr. Vijay K. Varadan
vjvesm@uark.edu,
vjvesm@engr.psu.edu

Keywords:

Nanomedicine, Nanodiagnosis, Nanopharmaceutics, Nanomaterials, Nanodevices, Nanosurgery, Toxicity.

Nanomedicine is generally defined as the medical applications of nanotechnology. Nanomedicine consists of five primary branches, including nanodiagnosis, nanopharmaceutics, implantable nanomaterials, implantable nanodevices, and nanosurgery. Before nanomedicine can be applied in clinical practice, the toxicity and environmental impacts should be investigated, and the ethical and social issues should be taken into full consideration.

1.1 Nanotechnology and nanomedicine


Nanotechnology involves the creation, manipulation and applications of materials and devices at the level of molecules and atoms. Research in nanotechnology began with discoveries of novel physical and chemical properties that only appear for structures at nanometer-sized dimensions. It is at this size scale that biological molecules and structures inside living cells operate. Understanding these nanoscale properties permits engineers to build new structures and use these materials in new ways. The same holds true for the biological structures inside living cells of the body. Researchers have developed powerful tools to extensively categorize the parts of cells in vivid detail, and we know a great deal about how these intracellular structures operate. In order to repair them or build new “nano” structures that can safely operate inside the body, fully understanding about cellular structures is needed. This will lead to better diagnostic tools and engineered nanoscale structures for more specific treatments of diseased or damaged tissues.

Nanomedicine is a subfield of nanotechnology. It is often defined as the repair, construction and control of human biological systems using devices built upon nanotechnology standards. Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve.The medical advances that may be possible through nanotechnology range from diagnostic to therapeutic, and everything in between. Nanomedicine seeks to deliver a valuable set of research tools and clinically helpful devices. New commercial applications in the pharmaceutical industry are expected that may include advanced drug delivery systems, new therapies, and in vivo imaging. Neuro-electronic interfaces and other nanoelectronics-based sensors are another active goal of research. Further down the line, the speculative field of molecular nanotechnology believes that cell repair machines could revolutionize medicine and the medical field. Of course, the full potential of nanomedicine is unlikely to arrive until after complex, high-sophisticated, medically programmable nanomachin-es and nanorobots are developed.

1.2 Nanomedicine Taxonomy


Nanomedicine exhibit great varieties, and many taxonomy approaches have been proposed [4, 5, 6, and 7]. In this review, we mainly follow the taxonomy proposed by Gordon and Sagman [4]. This nanomedicine taxonomy classifies some of the leading areas that nanotechnology tools, materials, devices, and intelligent materials and machines are currently applied in medical research, as shown in Table 1.

Table 1. Nanomedicine taxonomy

Branches

Areas

Nanodiagnosis

Imaging and visualization

 

Molecular characterization

 

Genetic testing

Nanopharmaceutics

Drug discovery

 

Drug delivery

Implantable nanomaterials

Structural nanomaterials

 

Tissue repair and replacement

Implantable nanodevices

Sensors and sensory aids

 

Medical devices

 

Neuro-electronic interfaces

Nanosurgery

Nanorobts

 

Surgical aids

Each primary branch of nanomedicine listed in Table 1 will be discussed in details in Sections 2 to 6 of this paper.

1.3 Status and prospects


1.3.1 Funding

Nanomedicine is a large industry, with nanomedicine sales reaching 6.8 billion dollars in this decade, and with over 200 companies and 38 products worldwide, a minimum of 3.8 billion dollars in nanotechnology research and development is being invested every year. Significant amounts of money are being invested in research. USA and European Union are investing billions of dollars and plan to invest more in the future. As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide. About 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. From the possible applications such as drug delivery and in vivo imaging to the potential machines of the future, advancements in nanomedicine are being made every day. It will not be long for the 10 billion dollar industry to explode into a 100 billion or 1 trillion dollar industry, and drug delivery, in vivo imaging and therapy is just the beginning.

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. 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 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.

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. 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.

2.1 Nanoparticle labels


Two types of nanoparticles, quantum dots and magnetic nanoparticles are widely used as labels in nanomedicine.

Nanoparticles such as quantum dot nanocrystals are in the size of a protein molecule or short stretch of DNA. Quantum dots can be engineered to absorb and emit many wavelengths of light with very sharp precision. This makes them ideal for protein-protein interaction studies as they can be linked to molecules to form long-lived probes. They can track biological events by tagging specific proteins or DNA in order to follow their progress through biological pathways. In medicine, quantum dots could be used for diagnostic purposes.

Dendrimers are another interesting and powerful use of nanotechnology in medicine. Dendrimers are nanostructured synthetic molecules with a regular branching structure projecting from a central core. Dendrimers form one layer at a time so the size of the dendrimer is determined by the number of synthetic steps. Each dendrimer is usually only a few nanometers wide. The outside layer can be engineered to be composed of specific functional groups that can act as hooks to specifically bind other molecules such as DNA. Dendrimers may act as effective agents for delivering DNA into cells during gene therapy. While viral vectors typically trigger an immune response, in principle, dendrimers should not.

2.2 Imaging and visualization


Two types of nanoparticles, quantum dots and magnetic nanoparticles are widely used as labels in nanomedicine.

The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging. Quantum dots (nanoparticles with quantum confinement properties, such as size-tunable light emission), when used in conjunction with MRI (magnetic resonance imaging), can produce exceptional images of tumor sites. These nanoparticles are much brighter than organic dyes and only need one light source for excitation. This means that the use of fluorescent quantum dots could produce a higher contrast image and at a lower cost than today’s organic dyes used as contrast media. The downside, however, is that quantum dots are usually made of quite toxic elements.

Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell walls. The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source.

In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast.

For MRI contrast enhancement, two types of nanomaterials are nanoparticles with a magnetic core, and fullerenes to encapsulate contrast agents such as gadolinium.

2.3 Nanosensors and nanochips


Various types of nanosensors and nanochips have been developed.

Sensor test chips containing thousands of nanowires, able to detect proteins and other biomarkers left behind by cancer cells, could enable the detection and diagnosis of cancer in the early stages from a few drops of a patient’s blood.

2.4 Lab-on-a-chip


A lab-on-a-chip device mainly consists of a sample preparation system, a sensing devices, and a reporting devices. DNA arrays typically perform one type of analysis thousands of times. In the event that other experiments or processes are also required, micro and nanofluidic devices such as lab-on-a-chip, can integrate mixing, moving, incubation, separation, detection and data processing in a small portable device.

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.

3.1 Drug discovery


High surface area to volume ratio, allows many functional groups to be attached to a nanoparticle, which can seek out and bind to certain tumor cells. Additionally, the small size of nanoparticles (10 to 100 nanometers), allows them to preferentially accumulate at tumor sites (because tumors lack an effective lymphatic drainage system). A very exciting research question is how to make these imaging nanoparticles do more things for cancer treatment. For instance, is it possible to manufacture multifunctional nanoparticles that would detect, image, and then proceed to treat a tumor? This question is under vigorous investigation; the answer to which could shape the future of cancer treatment. A promising new cancer treatment that may one day replace radiation and chemotherapy is edging closer to human trials. Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then “cooks” tumors inside the body with radio waves that heat only the nanoparticles and the adjacent (cancerous) cells.

Researchers at Rice University under Prof. Jennifer West have demonstrated the use of 120 nm diameter nanoshells coated with gold to kill cancer tumors in mice. The nanoshells can be targeted to bond to cancerous cells by conjugating antibodies or peptides to the nanoshell surface. By irradiating the area of the tumor with an infrared laser, which passes through flesh without heating it, the gold is heated sufficiently to cause death to the cancer cells. Additionally, John Kanzius has invented a radio machine which uses a combination of radio waves and carbon or gold nanoparticles to destroy cancer cells.

Nanoparticles of cadmium selenide (quantum dots) glow when exposed to ultraviolet light. When injected, they seep into cancer tumors. The surgeon can see the glowing tumor, and use it as a guide for more accurate tumor removal.

One scientist, University of Michigan’s James Baker, believes he has discovered a highly efficient and successful way of delivering cancer-treatment drugs that is less harmful to the surrounding body. Baker has developed a nanotechnology that can locate and then eliminate cancerous cells. He looks at a molecule called a dendrimer. This molecule has over one hundred hooks on it that allow it to attach to cells in the body for a variety of purposes. Baker then attaches folic-acid to a few of the hooks (folic-acid, being a vitamin, is received by cells in the body). Cancer cells have more vitamin receptors than normal cells, so Baker’s vitamin-laden dendrimer will be absorbed by the cancer cell. To the rest of the hooks on the dendrimer, Baker places anti-cancer drugs that will be absorbed with the dendrimer into the cancer cell, thereby delivering the cancer drug to the cancer cell and nowhere else (Bullis 2006).

In photodynamic therapy, a particle is placed within the body and is illuminated with light from the outside. The light gets absorbed by the particle and if the particle is metal, energy from the light will heat the particle and surrounding tissue. Light may also be used to produce high energy oxygen molecules which will chemically react with and destroy most organic molecules that are next to them (like tumors). This therapy is appealing for many reasons. It does not leave a “toxic trail” of reactive molecules throughout the body (chemotherapy) because it is directed where only the light is shined and the particles exist. Photodynamic therapy has potential for a noninvasive procedure for dealing with diseases, growths, and tumors.

3.2 Drug delivery


Drug delivery is currently the most advanced application of nanotechnology in medicine. Nanoscale particles are being developed to improve drug bioavailability, a major limitation in the design of new drugs. Poor bioavailability is especially problematic with newer and still experimental RNA interference therapy. Lipid or polymer-based nanoparticles are taken up by cells due to their small size, rather than being cleared from the body. These nanoparticles can be used to shuttle drugs into cells which may not have accepted the drug on its own. The nanoparticle may also be able to specifically target certain cell types, possibly reducing toxicity and improving efficacy.

Nanomedical approaches to drug delivery center on developing nanoscale particles or molecules to improve the bioavailability of a drug. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This will be achieved by molecular targeting by nanoengineered devices. It is all about targeting the molecules and delivering drugs with cell precision. The new methods of nanoengineered materials that are being developed might be effective in treating illnesses and diseases such as cancer. What nanoscientists will be able to achieve in the future is beyond current imagination. This will be accomplished by self assembled biocompatible nanodevices that will detect, evaluate, treat and report to the clinical doctor automatically.

Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacological and therapeutic properties of drugs. The strength of drug delivery systems is their ability to alter the pharmacokinetics and biodistribution of the drug. Nanoparticles have unusual properties that can be used to improve drug delivery. Where larger particles would have been cleared from the body, cells take up these nanoparticles because of their size. Complex drug delivery mechanisms are being developed, including the ability to get drugs through cell membranes and into cell cytoplasm. Efficiency is important because many diseases depend upon processes within the cell and can only be impeded by drugs that make their way into the cell. Triggered response is one way for drug molecules to be used more efficiently. Drugs are placed in the body and only activate on encountering a particular signal. For example, a drug with poor solubility will be replaced by a drug delivery system where both hydrophilic and hydrophobic environments exist, improving the solubility. Also, a drug may cause tissue damage, but with drug delivery, regulated drug release can eliminate the problem. If a drug is cleared too quickly from the body, this could force a patient to use high doses, but with drug delivery systems clearance can be reduced by altering the pharmacokinetics of the drug. Poor biodistribution is a problem that can affect normal tissues through widespread distribution, but the particulates from drug delivery systems lower the volume of distribution and reduce the effect on non-target tissue. Potential nanodrugs will work by very specific and well-understood mechanisms; one of the major impacts of nanotechnology and nanoscience will be in leading development of completely new drugs with more useful behavior and less side effects.

Nanoparticles are promising tools for the advancement of drug delivery, medical imaging, and as diagnostic sensors. However, the biodistribution of these nanoparticles is mostly unknown due to the difficulty in targeting specific organs in the body. Current research in the excretory systems of mice, however, shows the ability of gold composites to selectively target certain organs based on their size and charge. These composites are encapsulated by a dendrimer and assigned a specific charge and size. Positively-charged gold nanoparticles were found to enter the kidneys while negatively-charged gold nanoparticles remained in the liver and spleen. It is suggested that the positive surface charge of the nanoparticle decreases the rate of osponization of nanoparticles in the liver, thus affecting the excretory pathway. Even at a relatively small size of 5 nm, though, these particles can become compartmentalized in the peripheral tissues, and will therefore accumulate in the body over time. While advancement of research proves that targeting and distribution can be augmented by nanoparticles, the dangers of nanotoxicity become an important next step in further understanding of their medical uses. One important area in drug delivery is magnetic drug delivery.

Neuro-electronic interfaces are a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. The computers will be able to interpret, register, and respond to signals the body gives off when it feels sensations. The demand for such structures is huge because many diseases involve the decay of the nervous system (ALS and multiple sclerosis). Also, many injuries and accidents may impair the nervous system resulting in dysfunctional systems and paraplegia. If computers could control the nervous system through neuro-electronic interface, problems that impair the system could be controlled so that effects of diseases and injuries could be overcome. Two considerations must be made when selecting the power source for such applications. They are refuelable and nonrefuelable strategies. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or electrical sources. A nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained.

One limitation to this innovation is the fact that electrical interference is a possibility. Electric fields, electromagnetic pulses (EMP), and stray fields from other in vivo electrical devices can all cause interference. Also, thick insulators are required to prevent electron leakage, and if high conductivity of the in vivo medium occurs there is a risk of sudden power loss and “shorting out.” Finally, thick wires are also needed to conduct substantial power levels without overheating. Little practical progress has been made even though research is happening. The wiring of the structure is extremely difficult because they must be positioned precisely in the nervous system so that it is able to monitor and respond to nervous signals. The structures that will provide the interface must also be compatible with the body’s immune system so that they will remain unaffected in the body for a long time. In addition, the structures must also sense ionic currents and be able to cause currents to flow backward. While the potential for these structures is amazing, there is no timetable for when they will be available.

Virtually all disease, injury and wear to the body can be traced to the cellular level. Current medical technology does not provide a means for doctors to treat selective cells or “edit” disease from genetic code. Instead comparatively crude tools are used that themselves tax the body. Surgery, while lifesaving, is also an invasive process that causes the body significant stress. In many cases treatment involves removing entire segments of the body leaving a patient scarred or without the ability to bear children, all of which affects quality of life. If an organ is destroyed a patient is relegated to waiting on a donor list. Drugs often treat the byproduct of a problem, not the problem itself. At best, drugs affect the entire body rather than delivering medicine directly where it is needed. Chemotherapy indiscriminately kills cells, healthy and cancerous, yet cancer sometimes returns.
(In this section, the applications of magnetic nanotubes in neuron growth and regulation will be discussed.)

5.1 Nanorobots


At Rice University, a flesh welder is used to fuse two pieces of chicken meat into a single piece. The two pieces of chicken are placed together touching. A greenish liquid containing gold-coated nanoshells is dribbled along the seam. An infrared laser is traced along the seam, causing the two sides to weld together. This could solve the difficulties and blood leaks caused when the surgeon tries to restitch the arteries he/she has cut during a kidney or heart transplant. The flesh welder could meld the artery into a perfect seal.

The somewhat speculative claims about the possibility of using nanorobots in medicine, advocates say, would totally change the world of medicine once it is realized. Nanomedicine would make use of these nanorobots (e.g., computational genes), introduced into the body, to repair or detect damages and infections. According to Robert Freitas of the Institute for Molecular Manufacturing, a typical blood borne medical nanorobot would be between 0.5-3 micrometers in size, because that is the maximum size possible due to capillary passage requirement. Carbon would be the primary element used to build these nanorobots due to the inherent strength and other characteristics of some forms of carbon (diamond/fullerene composites), and nanorobots would be fabricated in desktop nanofactories specialized for this purpose.

Nanodevices could be observed at work inside the body using MRI, especially if their components were manufactured using mostly 13C atoms rather than the natural 12C isotope of carbon, since 13C has a nonzero nuclear magnetic moment. Medical nanodevices would first be injected into a human body, and would then go to work in a specific organ or tissue mass. The doctor will monitor the progress, and make certain that the nanodevices have gotten to the correct target treatment region. The doctor wants to be able to scan a section of the body, and actually see the nanodevices congregated neatly around their target (a tumor mass, etc.) so that he or she can be sure that the procedure was successful.

Nanorobotics or molecular nanotechnology involves the creation of complex mechanical systems constructed from the molecular level. Richard Feynman was the first to propose using machine tools to make smaller machine tools which can make smaller machine tools down to the atomic level. DNA makes an ideal material for the construction of nanomachines due to its stiffness. The intermolecular interactions of DNA are well-known and can be easily predicted. The self-assembly of DNA further facilitates its use as a construction material. Dr. Nadrian Seeman pioneered the use of DNA as a construction material and can make virtually any regular 3D shape. In 1999 his group succeeded in building the first nanoscale robotic actuator from DNA. DNA and later, nanotubes, have been used to construct molecular tweezers which can be used to physically manipulate nanostructures. Research into the construction of nanomotors has advanced greatly and nanomotors will form an important part of future nanorobots. Carlo Montemagno at Cornell has mutated the central rotating shaft of ATPase to have metal-binding amino acids that allow the ATPase to bind to nanoscale nickel pedestals. A silicon bar 100 nanometers long was bound to the rotor subunit of each ATPase by self-assembly, creating an ATP-powered molecular motor. These nanorobots may eventually form sophisticated cellular factories, used to synthesize drugs, repair damaged DNA, and releasing drugs on command.

Nanomedicine’s promise is to take humankind a giant step forward in how health is maintained and illness is treated. If born out, in vivo nanorobots would have the ability to travel directly to the problem cells and repair whatever malady exists at the cellular level without added trauma, pain, or disfigurement. Nanorobots are so tiny they would work in swarms, injected into the bloodstream in aqueous solution. For the first generations of people treated by nanomedicine, nanorobots might only perform very simple tasks. They might monitor body chemistry (for diabetics, for instance) or they might carry medicine directly to cancerous cells. Later incarnations of nanorobots are expected to eradicate disease through prevention at an early stage, making later drug treatments unnecessary.

It is believed that nanorobots will repair organs by traveling to the organ itself and regenerating healthy tissue where it is needed. Some scientists believe they will be able to reverse spinal damage and paralysis by repairing nerve, cartilage and bone. Regeneration of limbs will ultimately be possible. It may even be possible to reverse the aging process itself by repairing, and perhaps preventing, age-related wear on the body. The human lifespan and quality of life is expected to extend far beyond its current state. Eventually healthcare would operate from a wholly preventative posture. With a simple means of early detection and repair, there would be far less sickness to treat.

Using drugs and surgery, doctors can only encourage tissues to repair themselves. With molecular machines, there will be more direct repairs. Cell repair will utilize the same tasks that living systems already prove possible. Access to cells is possible because biologists can stick needles into cells without killing them. Thus, molecular machines are capable of entering the cell. Also, all specific biochemical interactions show that molecular systems can recognize other molecules by touch, build or rebuild every molecule in a cell, and can disassemble damaged molecules. Finally, cells that replicate prove that molecular systems can assemble every system found in a cell. Therefore, since nature has demonstrated the basic operations needed to perform molecular-level cell repair, in the future, nanomachine based systems will be built that are able to enter cells, sense differences from healthy ones and make modifications to the structure.

The possibilities of these cell repair machines are impressive. Comparable to the size of viruses or bacteria, their compact parts will allow them to be more complex. The early machines will be specialized. As they open and close cell membranes or travel through tissue and enter cells and viruses, machines will only be able to correct a single molecular disorder like DNA damage or enzyme deficiency. Later, cell repair machines will be programmed with more abilities with the help of advanced AI systems.

Nanocomputers will be needed to guide these machines. These computers will direct machines to examine, take apart, and rebuild damaged molecular structures. Repair machines will be able to repair whole cells by working structure by structure. Then by working cell by cell and tissue by tissue, whole organs can be repaired. Finally, by working organ by organ, health is restored to the body. Cells damaged to the point of inactivity can be repaired because of the ability of molecular machines to build cells from scratch. Therefore, cell repair machines will free medicine from reliance on self repair.

6.1 Toxicological concerns


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 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.”

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. The Europeans in general are more sympathetic to the precautionary principle than is the case in the US. In the EU, there seems to be more concern about potential problems and therefore more discussion prior to the technology being developed.

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.

The authors hope that this review might help young researchers and students getting excited about Nanotechnology and Nanomedicine Research and contributing to the International Journal of Nanotechnology and Nanomedicine Research.

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[2] Freitas, R. A., 2003, Nanomedicine, Vol. IIA: Biocompatibility, Landes Bioscience, Georgetown.
[3] Varadan, V. K., Chen, L. F., and Xie, J. N., 2008, Nanomedicine: Design and Applications of Magnetic Nanomaterials, Nanosensors and Nanosystems, Wiley, Chichester.
[4] Gordon, N., and Sagman, U., 2003, Nanomedicine Taxonomy, Canadian NanoBusiness Alliance, Toronto.
[5] Morrow, K. J., Bawa, R., and Wei, C. M., 2007, “Recent advances in basic and clinical nanomedicine”, Medical Clinics of North America, 91(5), pp. 805-843.
[6] Jotterand, F., 2007, “Nanomedicine: how it could reshape clinical practice”, Nanomedicine, 2(4), pp. 401-405.
[7] Freitas, R. A., 2005, “What is nanomedicine?”, Nanomedicine: Nanotechnology, Biology, and Medicine, 1, pp. 2- 9.

Published: 09 May 2017

Copyright:

Copyright: © 2017 Dr. Vijay K. Varadan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.