American futurist and Google's chief engineer Ray Kurzweil predicts that medical nanorobots will connect the human brain to the cloud brain (cloud computing system) in the future, thereby improving human intelligence and extending human lifespan.
With the continuous advancement of micro- and nanotechnology and the progress of interdisciplinary science, research on micro- and nanorobots has developed rapidly in the past decade. The driving methods of micro- and nanorobots have evolved from chemical fuel-driven to chemical fuel-free driving, the building materials have expanded from metals and artificial polymers to biocompatible and biodegradable materials, the research depth has deepened from in vitro studies to in vivo studies, and the application scope includes drug delivery, bone repair, photothermal therapy, thrombus removal, and toxin clearance, etc.
Not long ago, Wu Zhiguang, associate professor at the Center for Micro-Nano Technology Research, Institute of Basic and Interdisciplinary Sciences, Harbin Institute of Technology, collaborated with Professor P. Fischer's team at the Max Planck Institute for Intelligent Systems in Germany to achieve for the first time controllable and efficient swarm motion of nanorobots in the vitreous humor of the eye. The research results, titled "Swarm-Lubricated Micro-Thrusters Traversing the Intraocular Vitreous Hull," were published online in Science Advances.
Addressing the pain points of ophthalmological treatment
With an aging population and the increasing presence of screens in daily life, the incidence of eye diseases is rising. However, due to the presence of multiple blood-eye barriers within the human eye, conventional drug delivery methods struggle to reach the posterior part of the eyeball.
Wu Zhiguang explained to the China Science Daily that the droplet method has difficulty crossing the barrier between the lens and the vitreous body, while the blood transport method is also limited due to the obstruction of the blood-retinal barrier.
"Currently, the industry believes that intravitreal injection of drugs is a relatively efficient method. However, the drugs diffuse very slowly in the vitreous body and lack targeting. These biological barriers result in low efficiency and lack of targeting when delivering drugs to the retina," said Wu Zhiguang. He added that surgical treatments, because they directly affect the eyes, put patients under both physical and mental stress, and the recovery time is long, affecting their daily lives.
For the reasons mentioned above, the application of nanorobots in ophthalmic treatment has always been highly anticipated: First, their extremely small size allows them to be injected into the eye through a pinhole with a diameter of only micrometers, minimizing the impact on the eye and requiring no additional rest, making them a non-invasive treatment; second, nanorobots can move freely within the vitreous humor of the eye, traversing the vitreous barrier and carrying drugs to the target area of the retina, which scientists have high hopes for.
Ophthalmic nanorobots that can move freely
Achieving movement of nanorobots within the vitreous body is not easy. From a macroscopic perspective, the vitreous body is a viscoelastic fluid similar to a gel, while from a microscopic perspective, the main body of the vitreous body is a three-dimensional mesh with collagen as the main framework and water and hyaluronic acid embedded inside.
"Therefore, we envisioned that if nanorobots could traverse the three-dimensional mesh of the vitreous body, it would be possible to achieve controllable movement of nanorobots within the vitreous body." Since 2016, Wu Zhiguang and his colleagues have conducted numerous experiments on how to achieve intraocular movement of nanorobots. They ultimately designed a helical magnetic nanorobot with a surface coated with a nano-liquid lubricating layer, with a diameter of only 500 nanometers.
Wu Zhiguang explained that this nanorobot resembles a tadpole of nanometer size, consisting of a spherical head about 500 nanometers in size and a spiral tail about 2 micrometers in length. A magnetic material for magnetic actuation is located between the head and tail. Under the influence of an external rotating magnetic field, this nanorobot can move back and forth by rotating itself, much like bacteria. Furthermore, the movement of the nanorobot can be controlled by adjusting the external magnetic field.
At the beginning of their research, the team was unable to find any way to observe the movement of even a single nanorobot. Furthermore, the nanorobots were too small to understand what was happening. Ultimately, they devised a "large-scale observation" approach, starting with relatively simple and fundamental research, creating numerous macroscopically visible magnetic structures to facilitate observation.
Wu Zhiguang stated that it was the observation of the movement behavior of these macroscopic magnetic structures in glass that provided experience for the later ability of nanorobots to move in glass.
New difficulties arose one after another. During the experiment, even though the size of the nanorobots was smaller than the three-dimensional mesh within the glass, they still could not move within the glass. What could be the reason for this?
"Our observations under a microscope revealed that the nanorobots in the vitreous body could not rotate a full circle under an external rotating magnetic field as they would in pure water. We speculate that this may be caused by the entanglement of the nanorobots by biomolecules in the vitreous body," said Wu Zhiguang.
To address the entanglement problem, the research team explored various modification methods to help the nanorobots escape the entanglement of biomolecules. They ultimately conceived of using a liquid lubrication interface inspired by the pitcher plant. This pitcher plant-like lubrication interface allows the nanorobots to break free from the entanglement of biomolecules within the glass, ultimately enabling controllable movement of the nanorobots within the glass.
Medical nanorobots are viewed favorably.
This ophthalmic nanorobot has achieved controllable movement within a real pig eyeball. Wu Zhiguang explained that pig eyes are very similar to human eyes in terms of biological composition and size, making them an ideal research model.
In the experiment, researchers injected nanorobots into pig eyes, activated an external rotating magnetic field, and used optical coherence tomography (OCT), a technique commonly used in ophthalmology, to observe the nanorobots' position on the retina. The results showed that, through the controlled guidance of an external magnetic field and optical tomography, nanorobots can be manipulated to precisely accumulate in a very small area of the retina, providing a foundation for future research on targeted drug delivery using nanorobots.
Professor Tu Yingfeng of Southern Medical University commented, "Currently, most drugs, after entering the human body, mainly diffuse to the affected area through the circulatory system. This method has drawbacks such as low efficacy and significant side effects, especially since there has been no good solution for dealing with multiple biological barriers in the body. To address this problem, self-propelled nanorobots are considered capable of overcoming biological barriers and actively transporting drugs, a revolutionary technology that will revolutionize biomedicine and has thus become an important direction in the field of biomedical technology. This biomimetic, lubricated intraocular nanorobot enables controllable movement of nanorobots within the eye, allowing them to traverse the vitreous humor to reach the target area of the retina without causing damage. This technology has broad application prospects."
Industry experts emphasize that the most important and urgent application of nanorobots in the medical field is currently. However, medical nanorobots are still in the research and development stage and have not yet entered clinical use; many supporting technologies need to be developed and improved.
Taking ophthalmic nanorobots as an example, Wu Zhiguang said that the current direction of movement control still relies on manual manipulation of external magnetic fields. The research team has recently been working with experts in the fields of control and navigation in the hope of developing intelligent nanorobots like self-driving cars.
How will nanorobots develop in the future? Huang Xiaoqiu, a researcher at the Faculty of Engineering at Tohoku University in Japan, divides their development into three stages: "The nanorobots currently under development belong to the first generation, which are organic combinations of biological and mechanical systems. This generation of nanorobots can be injected into human blood vessels for health checks and disease treatment; the second generation of nanorobots are directly assembled from atoms or molecules into nanoscale molecular devices with specific functions, capable of performing complex nanoscale tasks; the third generation of nanorobots will include strong artificial intelligence and nanocomputers, and will be an intelligent device capable of human-computer dialogue."
Nanotechnology will no longer be just high-tech gadgets for superheroes in Hollywood blockbusters, but will genuinely benefit human life. American futurist and Google's engineering director, Ray Kurzweil, predicts that medical nanorobots will connect the human brain with cloud brains (cloud computing systems), thereby enhancing human intelligence and extending lifespan. By 2030, nanorobots will have settled within the human body, circulating throughout the body via the bloodstream, becoming part of human-machine integration.
