Your mother was right; good things do come in small packages, sometimes so small that a conventional lab microscope cannot see them. Nanotechnology, the science of the extremely tiny, has become the new high-tech frontier and an important emerging industry with a projected annual market of around one trillion US dollars by 2015.
Although serious work on this infinitesimally small order of magnitude only commenced in laboratories about ten years ago, scientists now project revolutionary advances in the medical, pharmaceutical, diagnostics and imaging sectors arising from the application of nanotechnology to health.
By all accounts, nanomedicine will constitute one of the most exciting fields of study in medicine in the coming decades. This fast-developing and increasingly lucrative field, which involves manipulating atoms and molecules to create tiny devices, smaller than one-thousandth the diameter of a human hair, holds extraordinary promise for the diagnosis, prevention and treatment of disease.
A nanometre is one-billionth of a meter, and it is at this size scale – about 100 nanometres or less – that biological molecules and structures inside living cells operate. More than just an extension of "molecular medicine," nanomedicine aims to employ nanoscale machine systems to address medical problems, and to maintain and improve human health at the molecular scale.
The European Science Foundation believes that nanomedicine is about to deliver “a healthcare paradigm shift” in which it will be possible to monitor people on the basis of known genetic predispositions, diagnose disease before there are any symptoms, administer drugs that are precisely targeted, and use non invasive imaging tools to demonstrate that the treatment was effective.
A recent ESF report notes that Europe is particularly strong in many areas of nanotechnology needed for advances in nanomedicine and that several European companies are at the cutting-edge of research in this area.
Bringing together experts from all over Europe and further afield, a new EU NANOMED project was launched in February this year to examine all aspects of nanomedicine and provide an objective answer to claims that this rapidly evolving field will change the face of healthcare forever.
The panel will for the first time look at all aspects - Economic, Patient Attitudes, Regulatory, Ethics and Communication - and enable EU policy makers to properly direct what has already been identified a major area for strategic investment in the new Framework V11 programme. The final report will be presented at the end of the year.
“Working at the nanoscale is already leading to new highly targeted medicines, improved imaging and diagnostics of disease and even a new generation of implantable sensors for monitoring your health,” surmises Professor Sir John Beringer, who is chairing the project.
In terms of therapy, one of the most significant impacts of nanomedicine will mostly likely be realised in drug delivery. Nanoparticles can enable doctors to target drugs at the source of the disease, which increases efficiency and minimises side effects. The first nanotechnology-based targeted drug delivery systems are already on the market, with numerous others in clinical trials or under development. Drug delivery accounts for approximately 80 percent of global sales in nanomedicine and 58 percent of patent filings worldwide. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide.
Some recent advances in this area include a potential new arsenal for meningitis treatment and the war on drug-resistant bacteria and fungal infections with the development of novel peptide nanoparticles by scientists at the Institute of Bioengineering and Nanotechnology (IBN) of Singapore.
The unique chemical structure of these stable bioengineered nanoparticles provides for the first time membrane-penetrating components on their surface, which allows them to traverse the blood brain barrier, offering a superior alternative to existing treatments for brain infections.
Pre-clinical tests, reported recently in Nature Nanotechnology, have shown that IBN's peptide nanoparticles are also biocompatible and cause no damage to the liver or kidneys at tested doses.
In the battle against cardiovascular disease, researchers and engineers in California have developed a nanoparticle that specifically detect and attack atherosclerotic plaques. The new development is described in a recent issue of the Proceedings of the National Academy of Sciences.
The nanoparticles in this study are lipid-based collections of molecules that form a sphere called a micelle. The micelle has a peptide, a piece of protein, on its surface, and that peptide binds to the surface of the plaque.
This tiny technology is also taking on cancer, in a very big way. Much of this pioneering research in recent months is focusing on targeting cancer with 'smart bombs'. Scientists at the University of Central Florida (UCF) have just released details about their newly engineered nanoparticles with a dual role, as diagnostic and therapeutic agents, that could someday target and destroy tumours, sparing patients from toxic, whole-body chemotherapies.
The researchers used Taxol - one of the most widely used chemotherapeutic drugs - for their cell culture studies, just published in the journal Small. Taxol normally causes many negative side effects because it travels throughout the body and damages healthy tissue as well as cancer cells. However, the Taxol-carrying nanoparticles engineered in the UCF laboratory are modified so they carry the drug only to the cancer cells, allowing targeted cancer treatment without harming healthy cells. This is achieved by attaching a vitamin (folic acid) derivative that cancer cells like to consume in high amounts.
In addition, the nanoparticles carry a fluorescent dye and an iron oxide magnetic core so that their locations within the cells and the body can be seen by optical imaging and magnetic resonance imaging (MRI). That allows a doctor to see how the tumour is responding to the treatment.
The nanoparticles also can be engineered without the drug and used as imaging (contrast) agents for cancer. If there is no cancer, the biodegradable nanoparticles will not bind to the tissue and will be eliminated by the liver. The iron oxide core will be utilised as regular iron in the body.
In a feat of trickery, immunologists at Dartmouth Medical School in New Hampshire, USA, recently devised a Trojan horse to help overcome ovarian cancer, unleashing a surprise killer in the surroundings of a hard-to-treat tumour.
Using nanoparticles, the team has reprogrammed a protective cell - the dendritic cells - that ovarian cancers have corrupted to feed their growth, turning the cells back from tumour friend to foe.
Their research, published online July 13 for the August Journal of Clinical Investigation, offers a promising approach to orchestrate an attack against a cancer whose survival rates have barely budged over the last three decades.
The National Cancer Institute – the US Government’s principle agency for cancer research – fully recognises nanomedicine’s massive potential, creating the Alliance for Nanotechnology in Cancer in the hope that its multi-million dollar investment in this branch of nanomedicine could lead to breakthroughs in terms of detecting, diagnosing, and treating various forms of cancer.
This enterprise is already producing results; in recent weeks researchers involved in a MIT/Harvard collaboration announced the development of an implantable diagnostic device offering continuous cancer monitoring, while scientists at the University of Massachusetts have devised a “chemical nose” array of nanoparticles and polymers to differentiate not only between healthy and cancerous cells but also between metastatic and non-metastatic cancer cells.
And there is progress towards drug-free cancer treatment as nanoparticle-based photothermal ablation is showing extraordinary promise as an unusually effective and potentially revolutionary cancer therapy.
This approach uses light at near-infrared wavelengths that pass through tissue, in combination with gold-based nanoparticles specifically engineered to absorb that light and convert it to heat.
The light-absorbing nanoparticles serve as highly localised heat sources that destroy cells in their immediate vicinity by hyperthermia. This method has been shown to be highly effective in extensive animal studies, with tumour remission rates above 90 per cent.
The US FDA recently granted approval for initial human trials of this therapy for head and neck cancer.
Researchers at the University of California recently presented their pioneering work in this area to the American Chemical Society's 237th National Meeting in March this year. They have developed the first hollow gold nanospheres - smaller than the finest flecks of dust - that search out and "cook" cancer cells far more effectively than their sold gold counterparts.
These new cancer-destroying nanospheres show particular promise as a minimally invasive future treatment for malignant melanoma, the most serious form of skin cancer, the researchers say.
The hollow gold nanospheres are equipped with a special "peptide." That protein fragment draws the nanospheres directly to melanoma cells, while avoiding healthy skin cells. After collecting inside the cancer, the nanospheres heat up when exposed to near-infrared light, which penetrates deeply through the surface of the skin. In recent studies in mice, the hollow gold nanospheres did eight times more damage to skin tumours than the same nanospheres without the targeting peptides.
The next step is to try the nanospheres in humans. This requires extensive preclinical toxicity studies. The mice study is the first step, but the researchers acknowledge there is a long way to go before it can be put into clinical practice.
However, the first human trials of nanoparticle-delivered 'suicide' genes that can slow and even halt ovarian tumour growth are expected to commence within 18 to 24 months according to a report in Cancer Research, a journal of the American Association for Cancer Research. US researchers revealed that nanoparticle delivery of diphtheria toxin-encoding DNA selectively expressed in ovarian cancer cells reduced the burden of ovarian tumours in mice. A number of the treated tumours failed to grow at all.
"This report is definitely a reason to hope. We now have a potential new therapy for the treatment of advanced ovarian cancer that has promise for targeting tumour cells and leaving healthy cells healthy," said lead researcher Prof Janet Sawicki from the Lankenau Institute for Medical Research in Pennsylvania.
Another highly attractive area of nanomedicine is diagnostics at nanoscale. The aim is to identify a disease at the earliest possible stage. Ideally, a single cell with ill behaviour would be detected and cured or eliminated.
Making enormous strikes in this area is a research team at the University of Nottingham who are developing revolutionary ultrasonic nanotechnology that could allow scientists to see inside a patient’s individual cells to help diagnose serious illnesses.
The components of this new technology would be many thousand times smaller than current systems. Ultrasound refers to sound waves that are at a frequency too high to be detected by the human ear, typically 20 kHz and above. Medical ultrasound uses an electrical transducer the size of a matchbox to produce sound waves at much higher frequencies, typically around 100 to 1000 times higher to probe bodies.
The Nottingham researchers are aiming to produce a miniaturised version of this technology, with transducers so tiny that you could fit 500 across the width of one human hair, which would produce sound waves at frequencies a thousand times higher again, in the GHz range.
Dr Matt Clark of the Ultrasonics Group in the university’s Division of Electrical Systems and Optics explains: “To produce nano-ultrasonics you have to produce a nano-transducers, which essentially means taking a device that is currently the size of a matchbox and scaling it down to the nanoscale. How do you attach a wire to something so small?
“Our answer to some of these challenges is to create a device that works optically — using pulses of laser light to produce ultrasound rather than an electrical current. This allows us to talk to these tiny devices.”
Tissue engineering and nano-scaffolding:
New concepts for nanotechnology in regenerative medicine give hope to many patients with organ failure or severe injuries. An extraordinary revelation by American military researchers in December last year took many by surprise when they claimed to have unlocked the secret to regrowing limbs and recreating organs in humans who have suffered major injuries.
Using "nanoscaffolding", Army researchers said they had regrown a man's fingertip and the internal organs of several test subjects. Their pioneering work was revealed officially at the 26th Army Science Conference in Florida in December 2008.
A very fine apparatus, a scaffold, made of polymer fibers hundreds of times finer than a human hair, are put in place of a missing limb or damaged organ. The nanoscaffold guides cells to grab onto it so they can begin to rebuild missing bones and tissue. Over time, the scaffold breaks down and is naturally passed from the body.
Dr John Parmentola, director of research and laboratory management for the US army, explained that by using nanoscaffolding the military was able to regrow a man's fingertip, restoring everything he had lost - the nail, the bone, the tissue.
Dr Parmentola added the military has been able to regrow "whole bladders" in people who have had bladder damage. The technology has also been used to repair the wall of a woman's uterus.
Several breakthroughs with nanoscaffolding preceded the US army's stunning announcement. Back in June 2006, researchers from the University of Sheffield in England used nanoscaffolding to repair skin damage in people with third-degree burns and they discovered that skin cells will “sort themselves” into the right arrangement if given a proper foothold.
In February 2008, a PhD student from Monash University in Melbourne, Australia, unveiled research into how nanoscaffolding could repair nerve damage. And later that year, researchers at the City University of Hong Kong, reported claims that nanoscaffolding would soon revolutionise bone grafts and implants.
While it is difficult to find fault with a technology that promises to cure cancer almost before it starts and prevent the spread of deadly infectious diseases, there are toxicological concerns and ethical issues that come with nanomedicine and they have to be addressed alongside the benefits.
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.
Although nanoparticles have been linked to lung damage, for example, it has not been clear how they cause it. However, this summer Chinese researchers discovered that a class of nanoparticles being widely developed in medicine - ployamidoamine dendrimers (PAMAMs) – can cause lung damage by triggering a type of programmed cell death known as autophagic cell death.
Also, they were able to block the process by using an autophagy inhibitor to prevent the cell death and counteracted nanoparticle-induced lung damage in mice. Their study is published in the newly launched Journal of Molecular Cell Biology.
A group of academics and industrialists in the US recently collaborated on a unique blueprint that will serve to educate the first generation of nanobiologists on the known physical and chemical properties of nanomaterials as well as particulars on the nano-bio interface. The authors’ analysis, published in the July issue of the journal Nature Materials, should help identify the potential risks of engineered nanomaterials and to explore design methods that will lead to safer and more effective nanoparticles for use in a variety of treatments and products.
The high-risk, high-payoff global nanotechnology phenomenon is in full swing. There is enormous excitement and expectation regarding nanotechnology’s potential impact on every aspect of society – even space travel. At NASA’s Ames Research Center, for instance, researchers are developing nano-based medical technologies that could be injected into astronauts to detect and kill cancers caused by the massive cosmic radiation exposure expected during a years-long manned Mars mission (proposed for launch in 2020).
The creation of nanodevices, such as nanobots capable of performing real-time therapeutic functions in vivo, is one eventual goal. Already this year researchers at Harvard University have created the smallest-yet nanodevice propulsion system. The corkscrew flagella nanoscale device mimics the way that some bacteria swim and overcomes some of the limitations of other proposed propulsion systems for nanoscale devices.
A mere 5,500 years took us from the wheel to the double helix. Then 50 years to the human genome. In the coming years significant research will be undertaken in various areas of nanomedicine – generating both evolutionary and revolutionary products. These efforts will traverse new frontiers to the understanding and practice of medicine. Even if we don't see the nanorobots of Fantastic Voyage fame for a few years, nanomedicine still has immense potential to impact all of our lives.