The latest “big thing” in medical research is unbelievably small. It is the world of nanomedicine, where drugs and devices are so tiny they are measured in a billionth of a meter, dwarfed by the smallest grain of sand.
Nanomedicine is a broad term that covers a wide range of applications, from pharmaceuticals to infinitesimally small particles that can be guided to an exact location in the body for diagnostic purposes or heated to destroy tumors, and even tiny robots that may one day circulate in patients’ arteries to remove heart-attack-inducing plaque.
“We’re entering an era of personalized medicine,” said Omid Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s Hospital in Boston. “We’re going to see much more specific and targeted agents that are smart and can go around the body, find disease and deliver therapeutics when needed but not when unnecessary.”
“WE’RE GOING TO SEE MUCH MORE SPECIFIC AND TARGETED AGENTS THAT ARE SMART AND CAN GO AROUND THE BODY, FIND DISEASE AND DELIVER THERAPEUTICS WHEN NEEDED.”OMID FAROKHZAD
DIRECTOR, LABORATORY OF NANOMEDICINE AND BIOMATERIALS, BRIGHAM AND WOMEN’S HOSPITAL
The potential benefits of nanomedicine have spawned dozens of new health care startup companies, often spinning out of university labs and funded by venture capital. Some predict the sector may rival the biologic revolution, which produced blockbuster drugs from biological sources such as recombinant DNA and created an industry now worth an estimated US$200 billion, according to IMS Health, an information and technology services company serving the health care industry.
THE POWER OF IMPERCEPTIBLE
Why is small better? Consider a disease like cancer. Current treatments usually involve some form of chemotherapy, powerful drugs that attack cancer tumors. Because they are absorbed generally throughout the body, however, chemotherapy drugs also cause a range of unwelcome side effects, from hair loss to heart damage.
In the International System of Units, “nano” means one-billionth. A sheet of paper is about 100,000 nanometers thick. A strand of human DNA is 2.5 nanometers in diameter.
Nanomedicine avoids such side effects by targeting only the tumor. For example, tumors build blood vessels with microscopic fissures a nanometer wide. Unlike traditional medicines with larger molecules, drugs manufactured into molecules a billionth of a meter in size can slip through these holes and accumulate, a process called the “enhanced permeation and retention” effect, or EPR.
“With enhanced permeation, the drug accumulates in the tumor more than in the healthy tissue, and retention means it gets in and stays there,” said Steve Rannard, a chemistry professor at the University of Liverpool and co-founder of the British Society for Nanomedicine.
Rannard has helped found three startup companies, including one that uses nanotechnology to reduce the molecular size of conventional drugs for treating HIV, which causes the disease AIDS. Because people with HIV must take drug therapies daily for the rest of their lives, dramatically reducing the size of the drug dosage will make the pills easier to swallow; reducing the dosage may also cut costs for governments and insurers that pay for the drugs. Rannard is working on an even smaller version of the medicine that can be injected into a patient’s muscle tissue, where it slowly releases over a period of weeks, making it easier for patients to adhere to their dosing schedule.
“If we can find ways that decrease the pill burden, you’ve got an area where nanomedicine can make a big contribution in the future,” Rannard said.
In India, scientists are using tiny polymer nanomedicines with molecules of RNA, the building blocks of life, to treat tuberculosis. The disease affected 2.2 million people in India in 2014, more than a fifth of the world’s cases, said Prajakata Dandekar Jain, an assistant professor at the department of Pharmaceutical Sciences and Technology at the Institute of Chemical Technology in Mumbai.
“We are working on molecules that are going to destroy the protein responsible for the survival of the tuberculosis bacteria,” Jain said. The nanomedicine will be so small that it can infiltrate through the cell wall of the mycobacterium tuberculosis, the bug that causes the disease. Jain’s lab is also using EPR to work on cancer treatments.
A FAST-GROWING FIELD
To manage nanomedicine’s complexity, research projects are bringing together scientists from a wide range of fields, including chemistry, physics, biology and engineering, and that is contributing to an explosion of research.
By 2000, when nanomedicine had existed for 20 years, the entire field had produced a total of just 1,200 research papers. Since then, the number of papers has doubled every year. Today, scientists are churning out 14,000 new studies and 125,000 papers annually .
Nanomedicine may prove revolutionary, Brigham and Women’s Farokhzad said, if it can convert drugs that must be injected into forms that can be taken orally. The challenge is that proteins such as those in many of the latest biologic drugs cannot pass through the digestive system, forcing patients to take the drugs intravenously. This makes compliance difficult because so many people hate being jabbed with large needles.
In hopes of changing this, Farokhzad’s team studied how nursing infants absorb human antibodies from breast milk. While early attempts to exploit this mechanism failed, Farokhzad said, his team managed to put thousands of molecules of insulin – which is almost always injected – on a nanoparticle, which is easily absorbed in the digestive tract. “We’ve got some pretty amazing results,” he said, paving the way for eventual oral insulin treatment.
To fight obesity, Farokhzad’s lab created nanoparticles that target fat tissue as other nanodrugs target cancer tumors. Instead of destroying the fat, the nanoparticles promote the formation of new blood vessels that help transform white adipose tissue, where fat is stored, into brown adipose tissue, a kind of “good fat” that burns energy. Mice given this treatment lost 10% of their body weight, offering hope for those with chronic obesity.
Instead of using the EPR method, the fat treatment used polymers specially encoded with targeting molecules. These molecules bind with proteins in the blood vessels surrounding fat tissue, but not with proteins found elsewhere in the body. “It’s a lot like using a GPS system to navigate in your car,” Farokhzad said.
Pharmaceuticals are not the only form of medicine where nanoparticles can make a contribution. One newly discovered treatment is to inject a patient with tiny particles of iron called super paramagnetic iron oxide nanoparticles, or SPIONs. Using magnets, SPIONs can be directed to a specific location in the body, such as a known tumor. Once in place, turning up the magnetic force heats the SPIONs and kills the tumor. The beauty of the process, Rannard said, is that the heat is localized inside the tumor, but does not damage other parts of the body.
A similar form of treatment has been tried with gold nanoparticles, because gold has a similar heating effect. Instead of using magnets, however, scientists heat the gold nanoparticles with an ultraviolet laser, which penetrates the skin. The heated nanoparticles destroy tumors without side effects.
Nanoparticles can also be deployed for non-invasive diagnostic imaging. For example, SPIONs can be deployed to show how blood vessels have developed in a tumor and surrounding tissue. The result is a kind of map that helps physicians determine the best treatment.
Another application marries technology from the Internet of Things with nanoparticles, a process dubbed “smart dust.” For example, Proteus Digital Health, a technology firm based in Redwood City, California, is already marketing a package called Proteus Discover. It consists of an ingestible sensor the size of a grain of sand that, when it reaches the stomach, transmits the data it collects to a small skin patch. In a different application, when attached to a small capsule of medicine, the sensor alerts health care professionals that the patient is taking their medicine as prescribed.
ARE NANO SURGEONS NEXT?
While many more applications are being explored, even more fantastic treatment are on the drawing boards. For example, scientists have developed nano-sized robots that can be directed by light or magnetism; the hope is they will be able to perform specific tasks, like removing arterial plaque. But those concepts are still many years away from being implemented.
“These things seem farfetched today, but they will be bread-and-butter applications a few decades from now,” Farokhzad said. “We’re already seeing the substantial benefits that nanomedicine can bring to patients.”
For more information on this emerging field, check out the Nanomedicine: Nanotechnology, Biology, and Medicine journal: