In 1959, Nobel-winning physicist Richard Feynman famously said: “There’s plenty of room at the bottom.” He was referring to the revolutionary potential of manipulating and controlling materials at the nanoscale.
During his classic talk, which took place at the annual meeting of the American Physical Society at the California Institute of Technology, he challenged the audience: “Why cannot we write the entire 24 volumes of the Encyclopaedia Britannica on the head of a pin?”
In the five decades since then, innovations in nanotechnology have given rise to batteries that last longer and electronic circuits with nanoscale features. Even in medicine, researchers have used nanoparticles to target disease precisely at the tissue, cellular or even molecular level – a field now commonly called nanomedicine.
Traditionally, medicines are small molecules that target one or more biological pathways. Futuristic nanomedicines, however, are combinations of drugs and materials (natural or synthetic), at the size range of 100-1000 nm – a thousand of them lined up in a row are roughly the diameter of a human hair. These materials, usually synthetic or natural polymers and lipids, are often used to package hydrophobic drugs and make them more soluble. These tiny “packets” of drug-filled nanoparticles travel in the bloodstream and unload the drugs at sites of disease.
Among the many inspiring innovations taking place in nanomedicine, here are five areas that we believe will experience significant growth in the years to come:
- Nanomedicine that responds to stimuli
Researchers have long tried to find ways to deliver therapeutic drugs to disease sites without affecting healthy tissue (and therefore minimizing side effects). It turns out that disease sites such as solid tumours have physiological features that differentiate them from healthy tissue. The local microenvironment of tumours, for example, has been shown to be more acidic and hotter than surrounding tissue, although this phenomenon has not been observed in all cases.
To call these nanoparticles “smart” is probably a bit of a stretch; they are, after all, not imbued with artificial intelligence. But researchers have developed nanoparticles that respond to stimuli that include pH, temperature and even enzymes that are overexpressed in the microenvironment of the cancer. For example, thermally responsive polymers swell and release their drug payload in the tumour microenvironment.
Apart from endogenous (internal) stimuli, nanoparticles can also be made to respond to external stimuli; a magnetic field, light or ultrasound, for example. Researchers have engineered nanoparticles that contain both iron oxide nanoparticles and anti-cancer drugs and concentrated them in tumours by using an external magnetic field.
- Nanomedicine that knows its destination
The pioneering work of Robert Langer at the Massachusetts Institute of Technology has made it possible for nanoparticles to stay in the blood circulation for significantly longer periods than before. By conjugating a synthetic polymer known as poly(ethylene glycol) (PEG) to nanoparticle surfaces, the nanoparticles were shown to circulate for up to 24 hours in the blood instead of only minutes.
Since the 1994 study, scientists have designed second and third generation nanoparticles that possess even more sophisticated characteristics: they have tethered antibodies, DNA or RNA aptamers, or small molecules to the surface of these PEG chains to send the nanoparticles to specific cancer tissue – think of it as writing an address on a postcard. For example, cancers are known to upregulate folate receptors on their cell surface; nanoparticles with folate molecules displayed on their surfaces are thus more readily taken up by these cancer cells.
- Nanomedicine manufactured in novel ways
It is critical that the nanoparticles be manufactured uniformly and reproducibly so that their properties can be well controlled. However, synthesizing millions – and billions – of precisely engineered nanoparticles is no easy feat.
Scientists led by Joseph Desimone at the University of North Carolina at Chapel Hill have developed a technique called particle replication in non-wetting templates (PRINT) to manufacture nanoparticles that are highly controlled for size, shape, surface chemistry and composition. In this method, nanoparticles are cast from a template and subsequently peeled off. Other synthetic techniques include the use of microfluidic devices to synthesize nanoparticles.
Nanomedicine researchers have adopted “green synthesis” methods to design metallic nanoparticles such as silver, iron, platinum and gold nanoparticles. By adding metal salts to the growth medium of bacteria, fungi and algae, the microbes become biological factories that convert the metal ions fed to them into nanoparticles.
- Nanomedicine that fights superbugs
The improper and excessive use of antibiotics has led to the evolution of antibiotic resistant bacterial strains, colloquially known as superbugs. Because our antimicrobial arsenal has not evolved as quickly as these superbugs, nanomedicine researchers have adopted clever approaches to tackle this growing public health problem.
Researchers led by Yi Yan Yang at the Institute of Bioengineering and Nanotechnology in Singapore, in collaboration with IBM Research, have developed a biocompatible and non-toxic hydrogel to coat surgical surfaces, instruments and implants.
Upon contact with contaminated surfaces, the hydrogel’s positive charge attracts negatively charged microbial membranes, rupturing the bacterium’s membrane and killing it. The hydrogel has been shown to kill several clinically relevant microbes within a minute of contact, including superbugs such as methicillin-resistant Staphylococcus aureus and multi-drug-resistant Mycobacterium tuberculosis.
- Nanomedicine that evades the immune system
Our immune systems are evolutionarily primed to eliminate objects that the body considers as “foreign”. This innate mass surveillance, however, also eliminates a good fraction of drug molecules we administer to treat disease.
To tackle this longstanding problem, researchers led by Liangfang Zhang from University of California San Diego took inspiration from nature and designed biomimetic nanoparticles. Very much like Harry Potter’s invisible cloak, by isolating the membranes of red blood cells and camouflaging polymer nanoparticles within them, the nanoparticles were rendered “invisible” to immune cells and circulated for longer in the bloodstream.
Dubbed “cell ghosts”, their longer residence time in the bloodstream reduces the need for frequent dosing. Zhang and colleagues have used the cell ghost nanoparticles in various applications that include bioremediation (removal of pollutants), vaccination and cancer drug delivery.
The Annual Meeting of the New Champions 2015 will take place in Dalian, China, from 9-11 September.
Author: Juliana Chan is an assistant professor at Nanyang Technological University in Singapore and a Young Global Leader. Sangeetha Krishnamurthy is a post-doctoral research fellow at Nanyang Technological University.
Image: A tray containing cancer cells sits on an optical microscope in the Nanomedicine Lab at UCL’s School of Pharmacy in London May 2, 2013. REUTERS/Suzanne Plunkett