Mini doctors in blood vessels: How far is the nano robot in reality?

Nano robot diagnosis for human disease

And the possibility of opening up the possibility

But before clinical clinical, it is still facing safety,

Drivers, body navigation and many other challenges

At the end of July, scientists from the French Institute of Health and Medical Sciences, the National Science Research Center and the University of Montpellier published an article on the nano robot they built with DNA in the "Nature · Communication" magazine. Scientists use nano robots to understand the molecular mechanism of cell mechanical sensitivity to study many biological and pathological processes.

As early as the science fiction movie "Wonderful Journey" released in 1966, people have a new imagination on the treatment of diseases: a single cell to repair and treat the human body to deal with the disease. In the movie, surgeons were narrowed to one million -in -one, and they entered the human body for vascular surgery by miniature submarine.

This is not a night. In the micro world, scientists hope that nano robots can reach places where humans cannot reach, such as blood. If they are put into clinical use, they will cruise, put drugs, and carry out micro -"surgery" in the human body at a scale of one billion meters ... to open up new possibilities for the diagnosis and treatment of human diseases.

In 2021, 16 years after the scientific problem that promoted basic scientific research was released before the last time the "Science" magazine was released, the magazine again released the world's most cutting -edge scientific issues. Among them, in the field of artificial intelligence, the first question is: Will the injection -resistant nano -robotic robot be a reality?

Almighty "doctor" in blood vessels

On the stage in the field of biotechnology, in the past two years, because of the new crowns worldwide, the most "beautiful scenery" is the MRNA technology: Pfizer/ Biontech and Modner's success, this new technology will take this new technology Pushing to the spotlight, the income of hundreds of billions of dollars makes it the most profitable "dark horse" in the history of pharmaceuticals.

Humans have found that MRNA (messenger ribonic acid) has been more than 60 years. However, this technology has made a slow progress in this technology. Entering the 21st century, the delivery technology of lipid nanoparticles (LNP) as a carrier, to a certain extent solve the problems such as MRNA's easy degradation and delivery efficiency in the body, so that the MRNA technology has developed rapidly and entered clinical applications.

Zhao Yiping, an outstanding research professor at the Department of Physics at Georgia University in the United States, told China News Weekly that since the rise of nanotechnology in the 1990s, a very important driving force that drove it to develop is the development of chips. However, the driving force in this field gradually turned to medical applications. In 2020, the Chinese Society of Micro -Microfin Technology wrote: The nano -biology combining nanotechnology and biomedicine will be an important part of the 21st century life science, and nano robots will also be the most seductive achievements in nano -biology.

However, unlike the "robot" we usually envision, nano robots are not some of the electronic devices such as batteries and chips and have a pair of metal armor. Today, even the most precise mechanical processing technology can not create traditional robots swimming in the body. Nano robots are synthesized and prepared through physical and chemical methods to prepare molecules and micro -nano materials with special structures and functions.

Tao Wei, assistant professor of Harvard Medical College and a professor at the Blagen Women's Hospital Affiliated to Harvard University, is a scientist in the direction of biomedical engineering. His research content focuses on the intelligent delivery system of drugs. Good transportation tools. In an interview with "China News Weekly", he said that there are actually many effective drugs in clinical practice, but one of the reasons is that the drug cannot accurately reach the lesion and releases the drugs. , Poor treatment effects and other issues.

In fact, in the past 30 years, the scientific community has found that the use of nanoparticles as a carrier to achieve accurate delivery of drugs has not achieved the expected results. After being wrapped in nanoparticles, after injection into the blood, it can only passively circulate with the flow of blood. There is no obvious difference from direct injection of drugs compared with the direct injection of drugs. The field is facing a more frustrated situation.

Scientists designed "nano robots" consisting of DNA origami structure. Figure/"Nature · Communication"

With the rise of nano robots, new progress has been made in accurate delivery of drugs. Nano robots can move independently in the human body, break through a series of biological barriers in the body, find the lesion site, and complete the drug delivery. It is an important part of the precision medical era.

Taking thrombolytic drugs as an example, Zhao Yiping introduced that there is a tissue protease in the blood that can prevent blood condensation. The elderly are easily condensed in a certain part due to physical function changes, especially the brain. As a treatment, doctors will quickly enter a TPA (tissue protease primary activated factor) in the patient's body, but it will flow throughout the body, which may cause the blood vessel wall to rupture a certain place in severe cases. The treatment efficiency is only 20 %. In 2018, his research team and partners reported a way to guide nano robots with magnetic force to allow these nanoparticles to assemble in the thrombus and then put the drugs. The thrombo -dissolving rate increases by 4 times.

For more tricky delivery parts, nano robots also showed positive potential in early breakthroughs. The brain is the most difficult place for nano robots to reach, because they need to pass through the blood -brain barrier -this is a very selective biological defense system that allows only some nutrients and specific molecules to pass the pathogens. Cerebal tumor is called "brain killer" and is one of the most tricky tumors in neurosurgery. Due to the special position of this tumor, it is difficult to perform thorough surgical resection, and residual tumor cells have become the root cause of future recurrence. If you want to treat this disease, the drug must pass through the blood brain barrier. After 8 years of hard work, He Qiang, a professor at Harbin University of Technology, designed a delivery strategy. They are putting anticancer drugs in magnetic nanogelry, and the gel's external bacterial membrane is "camouflage" and hidden in an immune cell called "neutral cells". Through the role of external magnetic fields and chemical fields, nano robots pass through the blood -brain barrier to achieve active targeted drug delivery in the part of brain gum tumor. The efficiency of ordinary nano -load delivery is about 0.7 %. This new method has increased the delivery efficiency of anti -tumor drugs to about 14 %. The article was published in "Scientific Robotics" last year, which is an important research progress in the industry. He Qiang said that future delivery efficiency is expected to break through.

Today, in the preliminary experiments, nano robot scientists around the world have used this miniature machine to treat various diseases. Tao Wei pointed out that in the field of medicine, in addition to drug delivery, nano robots can also be used for vaccine preparation, micro -tissue imaging, and disease testing. Because of its wide use, He Qiang pointed out that nano robots have a disruptive significance for the diagnosis and treatment paradigm of human future diseases. "In theory, nano robots can treat all diseases in the future."

About 10 years ago, when Zhao Yiping's parents were hospitalized at the same time because of stroke diseases, he began to be interested in how to use nano -robots in the field of stroke. In 2014, he published with the partner for the industry to use the nano robot for stroke treatment in the industry for stroke treatment with stroke treatment. The first paper. Generally speaking, disease treatment usually uses two methods of physics and chemistry, such as surgery and kidney stones is the former, and the drug is the latter. The nanotechnology designed by them also combines two methods of physical and chemistry. It is equipped with thrombolytic drugs on the robot. When they enter the stroke parts, in addition to releasing the drug, they can also use the mechanical effects of robots and thrombosis. Dredging blood vessels. This treatment idea is also known as "micro -nano surgery".

It is rarely noticed that in the field of condensing state physics, scientists also use microfanan robots as a model, called "active colloid" to study the formation and metastasis mechanism of tumors, as well as birds and fish groups Wait for complex group behavior in nature. This field of theoretical research has attracted widespread attention at home and abroad in recent years.

Driver and control of nano robots

Einstein has predicted that the development of science in the future is nothing more than continuing to march into the macro and micro -world. Nano -robot is practicing miniaturization to the end.

In 1959, in a well -known speech on nanotechnology, "There is a lot of space at the bottom of the material", the Nobel Prize winner Richard Fermann pioneered the early concept of nano robots. He believes that human beings may build a molecular -sized micro -machine in the future, which can use molecules and even a single atom as architectural components to build substances in a small space.

1 nanometer is 1 billionth of 1 meter, and about 50 microns width of the hair is also 50,000 times wider than a 1 -nanometer material. The size of nano robots is usually only tens to hundreds of nanometers. Beyond this range, it is difficult to produce sufficient driving force to promote their movements, and it becomes fatal thrombosis in blood vessels because of its large volume.

In "Magic Journey", a team of American doctors who narrowed the version of the American doctor boarded a submarine with a micron scale and entered the blood of the injured diplomat. Although the blood fluctuations caused by the heartbeat of the diplomat at each time, the submarine was on the edge of the submarine at any time, and the human antibody also regarded the submarine as an enemy to attack. The heroic protagonist was still able to manipulate the submarine to danger in the blood, and finally eliminated thrombus.

The best way to enter different parts of the body is the "highway" of the circular system -blood vessels. But for very, very small nano -machines, the blood flow of the human body is enough to rush them to "people upside down." The smaller the object, the greater the impact of air and water molecules, and the movement is very chaotic. Some scholars described that the movement of controlling nanoparticles is like controlling the fourth rotor drone to send the courier to the distant village in the storm.

Nano robots are a highly intersection of disciplines. The disciplines involve at least include biology, materials, physics, chemistry, artificial intelligence, micro -nano electronics, and so on. Since the beginning of the 21st century, people have synthesized many different types of micro -nano -materials and delicate elements. Scientific researchers can move these micro -nano -standard artificial molecules and particles independently through various methods such as chemical energy, electrical energy, magnetic energy, and light energy under various methods.

Magnetic power has always been the most mainstream way to drive nano -robots. On July 21 this year, an article published in "Nature · Machine Intelligence" stated that it was inspired by the internal protein motor movement of the biological cells along the cell microtubal movement. Micro -tube can quickly and reliable magnetic micro -nano robots in a complex body environment. E. coli, sperm cells, and grass ties, etc., swim in harsh environments and find food in a harsh environment. Some scientists also look for the inspiration of driving nano robots from nature. For example, the team led by the nano scientist Oliver Schmidt at the German Cairnitz Institute of Technology designed a hybrid robot based on sperm cells. Sperm is one of the fastest cells. Under the guidance of the magnetic field, the team uses sperm -assembled nano robots to transport the drug to the tumor occurrence of the female reproductive tract. In 2018, the paper published in the journal " On ACS NANO.

After the nano -robot is stable and autonomous, how to accurately "navigate" these micro -robots to a specific lesion site, there are two ideas. The first is like the idea of ​​driverless cars today. It is completed through algorithm control+imaging system. The former is responsible for designing and planning the best route to reach the destination, and the latter is tracking and positioning these miniature robots.

Another idea is closer to science fiction. He Qiang, a professor at Harbin University of Technology, introduced that it does not rely on external forces, but uses biological methods to let these miniature robots find the lesions themselves. For example, just like bacteria can rely on specific signals to find food. With the advancement of biomedicine, some biochemical signs released by the lesion can "guide" nano robots to go autonomously.

At the end of 2004, a papers published in the Journal of the American Chemistry Society first reported the nanotechnology -driven nanotechnology prepared by artificially prepared. Golden platinum nanoscope achieved autonomous movements by catalyzing hydrogen peroxide. The paper.

Through the blood vessels in the human body, nano robots can walk to different parts of the body. Figure/IC

In 2016, the Nobel Prize in Chemistry was awarded three scientists, the reason for the award was "design and synthesis of molecular machines." At that time, the Nobel Prize Judging Committee pointed out that at present, molecular machines are in the concept application stage, but in the future, it is expected to be used for more accurate disease testing, drug transmission, ultra -high -density information storage, energy storage, new materials, sensors and more and many such as. Fields, the application prospects are unlimited.

Around 2008, when He Qiang began to intervene in this direction, there were less than 10 papers published in the world. Now, He Qiang introduced that at least 50 research groups that specialize in nano robots have been specially studied in China. Zhao Yiping, one of the first Chinese scientists who carried out the research of nano -robotics and a professor of research professor at the Department of Physics at the University of Georgia, told China News Weekly that according to his observation, about half of the articles in the direction of micro -nano robots are published by domestic scholars.

In an article in January this year, the Wall Street Journal wrote that for decades, computer scientists and physicists have speculated that nanotechnology may completely reshape our lives at any time and launch a wave of "saving human" invention waves at any time. Essence "Although things have not developed as they predict, the nano -technology revolution is quietly carried out."

Since 2019, He Qiang said that the Ministry of Science and Technology is listed nano -robots as a new and important research direction of nano -medicine; among local governments, nano robots have also been written into official plans. Take Heilongjiang Province, where he is located as an example, in the "Fourteenth Five -Year Plan" Biological Economic Development Plan issued in March this year, Heilongjiang Province proposed to vigorously cultivate the 10 billion -level biomedical engineering industry demonstration base, including accelerating the development of nano robots , High -throughput biochemical analyzer, automated immunochemical analyzer and other high -end medical equipment.

Before clinical, there is still a long journey

Theoretically, nano robots can be self -degraded safely after the human body can start a journey through intravenous injection or oral intake to eliminate the source of the disease.

However, Zhang Ying and others of the Key Laboratory of the Molecular Structure and Nano Technology of the Chinese Academy of Sciences Zhang Ying and others wrote in a summary article published by the end of last year that in order to meet the actual needs of biomedical applications, nano robots are biological safety, drive, driver, driver, and There are still many challenges in many aspects such as navigation.

Taking safety as an example, Zhang Ying and others pointed out that nano robots enter the body's possible impact on the organism, and how to eliminate from the body after completing the task is worthy of attention. Choosing materials with good biocompatibility, biodegradation, and reliable and safe materials are the key.

In terms of body navigation, the current mainstream design is to accurately position and track the movement of nano robots in the body through imaging technology. However, He Qiang pointed out that the most advanced imaging system of the body can not yet "see" nano -level objects, that is, it is impossible to "watch" to a single nano robot. It can only be located in real time and path planning by tracking the nano robot cluster. And the speed of the imaging cannot keep up with the speed of nanoparticles in the blood. The breakthrough in this area is possible in the next 10 years.

In addition, nano robots still have many difficulties that have not yet been resolved. For example, Tao Wei pointed out that the human environment is more complicated than the environment of small animals. Various proteins in the blood may be adsorbed on nano robots, "covering" some of the original surface targeted or intelligent design, so that they The real delivery efficiency in the human body is not high enough. Another challenge is that the immune system may identify nano -robots as a threat to eliminate before they removed the loaded drugs. To solve this problem, scientists are also studying materials that will not cause immune response in our body. In Zhao Yiping's view, the current "nano robot" has engine and fuel, but there is no "brain". People cannot be intelligently used by chips and programming. "More appropriate.

The Chinese Micro -Micro -nanotechnology Society wrote in a popular science article published in 2020 that the nano robot currently developed is the first generation and is an organic combination of biological systems and mechanical systems. The nano -device with specific functions can perform complex nano -level tasks; the third -generation nano robot will contain strong artificial intelligence and nano computers, which is a smart device that can perform human -machine dialogue.

With the rapid progress of micro -nano -robotics, although it may cause ethical issues, it is also worthy of attention. In 2020, an article "The Environment and Health Risks of the Royal Institute of British Chemistry (RSC)" published on the website of the "Royal Institute of British" states that there are two potential hazards of this cutting -edge technology: one is that nano robots use harmful body to use harmful bodies The material and ultraviolet rays are the loss of force or targeted out of control. In addition, it is necessary to discuss how the current regulatory framework adapts to the development of nano robots.

Just like people's concerns about artificial intelligence, nano robots may also go out of control and change from the elimination of diseases to destroying our bodies. Self -media also expressed concerns about the growth rate of nano -robots beyond control and self -replication. Zhao Yiping pointed out to China News Weekly that this worry is not necessary at all. Because most of the preparation materials for nano robots are some life -free or organic materials, even robots assembled by DNA, because structural design and lack of enzymes such as enzymes cannot copy themselves.

"Many times the more advanced technology, the more potential threats may be greater." He Qiang said that scientific researchers cannot talk about the advantages of nano robots for the sake of funds, and do not talk about potential threats. In his opinion, after 10 years, the discussion of the ethics and legal norms around nano robotics will become very important matters.

Why the nano -robot has not yet advanced to the clinical trial stage, He Qiang said that the real reason is that from cell experiments, animal experiments to clinical trials, and a large number of R & D work to be completed, the cost is very high and long.

Some startups have begun to incubate this field. For example, in 2017, a headquarters of California startup Bionautlabs was established. The micro -robot developed by the company can be sent to the depths of the human brain to treat diseases that cannot be cured by other methods. In April of this year, according to the Daily Mail, the company plans to conduct first human clinical trials for its micro -injection robot within two years.

After the far -reaching public health incident, Tao Wei said that with the rapid approval and wide use of the MRNA vaccine, more and more people have begun to pay attention to the fields of nanoparticles and drug delivery technology. And capital began to actively invest in. "Tao Wei described," This feeling is like. It turned out that this field was slowly exploring on the countryside, and suddenly entered the highway. "

In March of this year, a article published in the magazine of "Nature", entitled "Micro -Medical Robotic Robots Jumping out of science fiction", obviously, to put the robot air to the tumor parts that are difficult to touch in the human body to the human body. ,there's still a long way to go. However, the rise of animal living experiments in this field and the participation of more and more clinicians show that micro -robots may be sailing and embarked on a long journey to clinical clinical.

(Intern Du Yin also contributed to this article)

Send 2022.8.15 Total Issue 1056 "China News Weekly" magazine

Magazine title: Mini doctor in blood vessels: How far is nano robot shot in reality?

Reporter: [email protected])

Edit: Du Wei

Operation editor: Xiao Ran

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