Nanobots are tiny biological machines that can deliver drugs to the target destination to make them more efficacious and reduce side effects, which are the biggest challenges of drug delivery.
Traditional drug treatments, for example cancer chemotherapy, can come with toxic compounds that indiscriminately damage healthy tissues. Nanobots could circumvent this issue by protecting the drug until it’s delivered to the intended target. The goal is getting the right dose to any part of the body without collateral damage.
To achieve this, nanobots are made by combining inorganic elements or materials with biological components, such as cells, proteins or DNA. This requires the collaboration of researchers from several branches of science. “In robotics we see materials scientists and biologists working more closely with us than ever, for good reason,” says Bradley Nelson, Professor of Robotics and Intelligent Systems at ETH Zürich. “We get insight into problems we were stuck on, such as new adhesives based on gecko feet and their use of van der Waals forces, or helical microrobots based on flagellated bacteria locomotion.”
Nanorobots could be inserted into human veins or ingested, and start a journey within our human body. They could motor through them or traverse the source of disease using astute biological disguises and mechanisms, and after finishing their mission, self-degrade safely.
Delivering drugs to their target
The best way to access different parts of the body is through the highways of the circulatory system: blood vessels. But it will not be an easy voyage for the nanobots. In the blood, there are many free-moving cells and other components that can hinder their movement.
Researchers at the Max Planck Institute for Intelligent Systems, in Stuttgart, created so-called ‘microrollers’ that can stick to the inner walls of blood vessels, even against blood flow, and can navigate blood vessels with the help of a magnetic field. The microrollers are coated on one side with magnetic materials used to move them through the body and on the other side with antibodies to recognize tumor cells.
Each part of our bodies presents its unique challenges for the robots. A research team at Purdue University have successfully piloted a biorobot through the colons of a mouse and a pig. The rotatory robot was controlled by a magnetic field and armed with a polymer coating that keeps the payload from acting on other organs before it reaches its target site.
Magnetic force has been the most popular way of directing nanobots to their targets. MagnebotiX, a spin-off of the ETH Zurich, develops magnetic field generators and micromagnetic agents for researchers working in this area.
Other external forces to move the robots have been used like sound, electricity, or even microorganisms such as bacteria, exploiting their ability to swim through biological environments and find favorable conditions. ‘DNA origami’ has also been used to create nanobots that can carry a payload and open when their target is found. Even immune and sperm cells have been studied as driving sources for biological robots. The latter, colloquially called spermbots, offer advantages for treating cervical cancer and gynecologic problems due to their natural ability to move in the female reproductive system.
The most difficult mission: reaching the brain
The brain is the hardest place in our bodies to reach. In order to do that, nanobots would need to cross the blood brain barrier, an extremely selective biological defense that allows just some nutrients and molecules to pass through, keeping pathogens out.
“There is work using ultrasound to cross the blood brain barrier, but we still cannot direct a drug across it as easily as we’d like. This would provide some advantages, but you still need to get the drug to the right place at the right time. And this assumes you have the right drug and can attach it to your nanobot somehow,” said Nelson.
In spite of these obstacles, there have been promising steps in this area. To treat glioma, a type of brain cancer, scientists from the Harbin Institute of Technology in China, designed ‘neutrobots’ that can travel inside the brains of mice and stop the growth of tumor cells. The team loaded the cancer drug paclitaxel into magnetic nanogels that can cross the blood brain barrier by hiding inside a type of immune cells known as neutrophils.
The future of nanobots for drug delivery
In the future, nanobots may integrate a variety of hybrid structures, cell and tissue types, building blocks of DNA strands and proteins, and a range of mechanisms that could give them sensitivity to different pathogens. They also could include vascular networks for transporting nutrients, and neural networks for sensing and processing information.
One branch of research focuses on creating xenobots: living robots made out of different types of cells, such as muscle cells for moving around and skin cells for interacting with the environment. “They can be much smarter than all of those [other nanobots], since they are made of skin cells which already have a lot of sensors, secretion machinery, computational machinery, etc. All this stuff that otherwise has to be created from scratch, these cells already have,” tells me Michael Levin, Professor of Biology and Director of the Allen Discovery Center at Tufts University.
While the first xenobots have been created using frog cells, in the future it might be possible to make them out of human cells. “Xenobots, once made from human cells, are ideal in the gut and other large spaces. They won’t cross the blood-brain barrier, but they can be smart to identify wounds, specific chemical signals, cancer cells, etc.” Levin comments.
Because a single nanobot can’t carry enough medication to treat a disease, researchers are also trying to understand how they can move as swarms. It could be hundreds, thousands, even millions of them, depending on the target. “Swarm robotics gives you advantages concerning robustness. Not all robots need to be successful for the system to be successful, and it allows each robot to carry small payloads that combine into sufficient payloads to get the job done,” said Nelson.
Using nanobots for drug delivery is still in early stages of research. Manufacturing at the nanoscale faces problems related to the fabrication, integration, and the interaction with complex biological environments. “There are groups moving in this direction in which nanobots will be used for drug delivery, but I think it takes a strategy to move into the clinic, not just a single research result and, voila, all problems solved”, said Nelson.
Scientists in the field still have many challenges to tackle, such as the limited lifespan of biobots, the lack of intelligent perception, and a lack of imaging techniques that can track nanobots in real time. Another challenge is that the immune system may identify them as threats to be eliminated before they can deposit their drug cargo — to address this, scientists are researching materials that do not trigger an immune response inside our bodies.
Overcoming these obstacles, humanity could have at its disposal armies formed by smart biological living machines, with adaptive skills to fight against diseases that are impossible to cure with current methods.
“There is massive suffering worldwide due to numerous health problems and disparities in healthcare,” Levin claims. “It cannot be addressed with traditional approaches, but requires true regenerative medicine.”