Nanomedicine could outdo surgery
Nanoparticles programmed to dispatch drugs to specific parts of the body could make surgery a thing of the past, writes David Tan
Imagine swallowing a pill of tiny molecular robots that can hone in on any injured part of your body and perform repairs. In 1959, the Nobel Laureate Richard Feynman predicted that we would one day be able to "swallow the doctor" to heal ailments from inside our bodies.
Today, nanotechnology is bringing the dream of that pill closer to reality. Medicines are being developed to be just like the small seeds of the burr plant, covered in tiny hooks that cling onto your socks as you walk through the grass. Submicroscopic nanoparticles are designed to bind tightly to specific targets within the body and release drugs slowly and steadily.
"If you put 1,000 nanoparticles side by side they are about the width of a human hair," says Dr Juliana Chan, adjunct assistant professor at the Nanyang Technological University (NTU) in Singapore.
Hong Kong University Professor So Kwok-fai specialises in neuroscience and has developed a nanoparticle in collaboration with MIT to support regeneration after nerve damage. Explaining why this treatment is needed, So says: "The central nervous system is unable to repair itself because the nerve microenvironment does not support neuron regeneration."
The nanoparticle is made by linking amino acids, the building blocks of protein. When the nanoparticles come in contact with blood, they self-assemble into a nanofibre scaffold. This scaffold can bridge gaps in damaged tissue and provide a framework for nerve regeneration. For example, So has tested his formulation on laboratory animals to repair optic nerveS, resulting in functional vision.
An unexpected finding was that the nanoparticles were able to stop bleeding, a major problem during neurosurgery. During a surgical experiment, So's team was surprised to find that the laboratory animal did not bleed after the nanoparticle solution was applied. They realised that the nanoparticles were an effective means to stop bleeding, which leads to faster recovery after surgery. "An analogy would be like beavers building a dam with wood instantaneously so the flow of water can be stopped right away," says So.
With the discovery of a way to stop bleeding almost instantly during neurosurgery, this important risk can be better managed. He says: "Normally it would take more than 90 seconds for platelets to amass at the site of the wound, form a blood clot and stop the bleeding. But the application of the nanomaterial was able to stop the bleeding within 15 seconds."
Dr Kenneth Wong, clinical assistant professor at HKU's Department of Surgery, studies the use of nanoparticles made from silver. His research focuses on applying silver nanoparticles to skin burns, surgical wounds and even bone fractures to help repair and regeneration. Wong's team has shown that silver nanoparticles can stimulate skin cells to grow and divide more rapidly to close a wound, as well as push underlying cells to help contract the wound. Silver nanoparticles are now incorporated into wound dressings for treatment.
Over in Singapore, NTU's Chan first started working on "nanoburrs" in Professor Robert Langer's laboratory at the Massachusetts's Institute of Technology (MIT) in the US, where she developed nanoparticles to deliver drugs to injured blood vessels. Nanoburrs are nanoparticles coated with a sticky protein that makes them cling onto artery walls while they slowly release drugs.
To treat atherosclerosis, which is caused by accumulation of fat within blood vessels that serve the heart, doctors may perform surgery and use a microscopic balloon to open up the narrowed blood vessels. However, this treatment could damage the artery walls and when the body repairs the damage, the blood vessels become narrow again. To prevent this, drugs are applied to limit the growth of scar tissue within the blood vessel.
Just 60 nanometres (or 60 billionths of a metre) wide, the MIT nanoparticles can carry a drug load and bind only to damaged parts of the blood vessels around the heart. They are made from materials that are compatible with the body and can be broken down harmlessly when finished.
Nanoburrs are layered like an onion. The outer coating protects the internal layers as the particle travels through the blood and is made from a material less easily detected by the body's immune system. This outer coating also comprises protein "hooks", like the outer covering of burr seeds, which can bind to specific targets in the body. The middle layer is a fatty material while the inner core contains the drug. Once bound, the nanoparticles release the drug gradually over a long period of time. This can be over days and weeks, which is much longer than when we take regular medication.
Chan believes that nanoparticles are making more drugs available.
"Nanoparticles have revolutionised the delivery of drugs. Drugs with poor profiles that were routinely discarded, for being too hydrophobic [water-repellent] for example, and previously had poor bioavailability can now be encapsulated in nanoparticles to improve their solubility and pharmacokinetic profiles."
Researchers at the Brigham and Women's Hospital in the US are also using nanoparticles to tackle inflammations. Inflammation is caused by large numbers of white blood cells infiltrating a site in the body. Prolonged excessive inflammation causes diseases such as atherosclerosis, arthritis and type 2 diabetes.
Nanoparticles carrying anti-inflammatory drugs and designed to attach to inflamed tissues are effective in delivering treatment to where it is needed. Because the nanoparticles release their anti-inflammatory cargo slowly over time and in a sustained manner, this form of treatment can be used to bring inflammation under control.
"These targeted polymeric nanoparticles are capable of stopping neutrophils, which are the most abundant form of white blood cells, from infiltrating sites of disease or injury at very small doses," says Dr Nazila Kamaly, co-leader of the research team.
"This action stops the neutrophils from secreting further signalling molecules, which can lead to a constant hyper-inflammatory state and further disease complications. We are excited about the potential of these nanomedicines in cardiovascular diseases, such as atherosclerosis."
Professor Ira Tabas of Columbia University in the US, says: "The beauty of this approach is that it takes advantage of nature's own design for preventing inflammation-induced damage, which - unlike many other anti-inflammatory strategies - does not compromise host defence and promotes tissue repair."
How safe are these nanoparticles to human health?
A key concern with any medical treatment is the potential toxic effects on the patient. This is especially important with nanoparticles because of their tiny size and ability to either escape immune detection or reduce the immune response. Scientists and doctors are working together to study the potential side effects of this new form of treatment.
Wong explains: "A lot of research has indeed been done on the toxicology of nanomaterials. However, these have been either done in in-vitro cultures (in laboratory dishes) or on animal experiments. Only with long-term use will we be able to see any potential problems in the future."
Nevertheless, the exciting advances being made in nanoparticle research are now making it possible for us to "swallow the doctor", making Richard Feynman's prediction a reality.