Put a micro robot to let the cell "what to hit"

Release date: 2018-07-11

Visual China

The futurist Ray Kuzwell is happy again.

This is what Bill Gates thinks is the most accurate prediction for the future. I said this a few years ago: "Under the microscope, I saw my white blood cells surrounding a pathogen and then destroying it, but it was too slow, the whole process needed One hour. I believe that in the future, nanobots can be transplanted into the body and do the same work in a matter of seconds."

Recently, Science and Robotics magazine published a miniature robot developed by scientists from the City University of Hong Kong to transport cells to a designated location under the control of magnetic force. The robot in the body of Kuzwell has a "eyebrow". Although it has no self-awareness and is controlled by the physical forces of the outside world, it has already made the prophecy a reality by virtue of the ability to let the cells "find which to hit" and "what to stop" in the living body. Big step.

The fate of the cell "following the flow" or being rewritten

“Return” is one of the main means of cell therapy. Injecting cells back into the human body is like putting a small boat back into the waterway. The human body is a densely-weaved “waterway network”. If there is no effective and powerful “navigation” equipment, it can only “follow the flow”. Unable to reach the cell treatment at the specified location, the efficacy will be greatly diluted or even not working.

Scientists have tried a variety of methods. "The use of chemical, biological, and physical forces can be used to achieve targeted cell placement." Yang Guanghua, a special expert in the National Thousand Talents Program, said that, for example, CAR-T cell therapy, which has been clinically applied, utilizes antigenic antibodies in organisms. The force generated by the reaction. By modifying a T cell (a type of immune cell), a "CAR" capable of recognizing a tumor by an antigen-antibody reaction is mounted thereon, and once the protein on the surface of the tumor cell is recognized by the CAR, it is "anchored" to the target tumor cell. On, play a role.

The micro-robot under magnetron uses physical force to control the cells. The research team of the City University of Hong Kong covers the surface of the carrier with nickel, so that the weak magnetic force can navigate or even anchor the cell "boat" that enters the "channel" of the blood vessel. "For example, using cells to repair soft tissue, to allow cells to root and grow where they need to be repaired, after the cell suspension has been injected into the human body, the cells may not be able to stay in the desired position, and there is always difficulty in locating. If the technology Really clinical, will solve this problem." Yang Guanghua said.

In addition to being able to locate the cell carrier, it is also necessary to solve the problem of loading. In order to transport the target cells as much as possible, the paper shows that the research team used computers to simulate the movement of different shapes of "cell carriers" in different blood vessels, and determined that the use of a hollow spherical configuration and extending the "antenna" can carry more cell.

"This research has given a new design idea and exploration direction in the field of cell therapy." Yang Guanghua believes that micro-robots, like trucks carrying rescue teams, must be able to "go in, get accurate, and get out." To validate these three points, the research team experimented with multiple viscous cultures, transparent zebrafish embryos, and mice, demonstrating that micro-robots created by 3D printing can sail, reach destinations, and carry cells The specified location is in effect.

To be able to "get in, get it right, come out"

If the human body is another "Avatar World", then scientists have never stopped trying to implement a precise impact on the world, and every design is exquisite. Whether it is targeted therapy or precise treatment, future medicines are striving to accurately attack or repair the lesions. The current "different world" control methods, including genes, proteins and even compounds, have their own "target" matches. Characteristic substances, as well as external field control forces such as ultrasonic, magnetic, optical, and force.

“Nano-gun technology combines the two types to complete the 'killing' of the tumor site.” As an industry promoter of cell therapy and gene therapy, Yang Guanghua’s “nano-gun” was completed more than a month ago. The first clinical trial of an elderly lung cancer patient. The "bullet" of the nano-gun is exquisitely designed, and it also needs to accomplish the three major tasks of "getting in, going right, getting it right".

To this end, the "bullet" consists of three parts, including a nitroimidazole, a drug delivery carrier made of nanomaterials, and a radioisotope 188.

The bombardment of external force helps the "bullet" airborne around the tumor site. The nitroimidazole in the drug can actively diffuse through the hypoxic cell lipid membrane of the tumor with strong reducing ability, so it can be accurately positioned. After anchoring the target, it is assembled. The nanocarriers made of lysine dendrimers immobilize the "kill target", allowing tumor cells to continuously ingest 铼188 and nitroimidazole. Nano-gun technology has been authorized by the international PCT worldwide and has been the most revolutionary patented technology for cancer treatment by the French Cancer Center.

Another fascinating design comes from the National Nanoscience Center of the Chinese Academy of Sciences. Scientists have created an "automated bomb" using DNA origami technology, which only explodes around the tumor.

The data show that with the development of DNA nanotechnology, DNA can be used as a folded configuration. A "bomb" consisting of four thrombin molecules carried by a flat rectangular DNA folded cardboard. It is wrapped into a hollow tube before explosion, and the thrombin molecules are encapsulated in the tube, and the nuclear expression of the tumor is highly recognized. The fixed-strand DNA fragment of rensu is bound, and only when it reaches the periphery of the tumor, the fixed chain is bound by the combination of nucleolin, and the "bomb" is also detonated, exploding the thrombin molecule, forming a huge blood vessel in the blood supply for the tumor tissue. Thrombosis, killing the tumor.

In addition, through the photodynamic therapy device of the photosensitizer and the light "inside", the light source is used to excite the photosensitizer to generate a large amount of singlet oxygen and simultaneously release the fluorescence, killing the cells that do evil in the body, and is constantly improving and clinical application. The use of ultrasound to deliver microvesicles carrying immune-related genes or antigens to tumor cells or immune cells will enhance the efficacy of tumor immunotherapy.

For clinical use, it also needs to address challenges such as metal toxicity.

"Micro-robots have their unique advantages and do not require specific binding sites. They are a 'universal' cell-carrying technology." Yang Guanghua said that it has great potential, but further exploration is needed to solve the problem in clinical applications. Removal and nickel-titanium toxicity issues.

According to a paper from the General Hospital of the People's Liberation Army entitled "Carcinogenic Mechanism of Nickel and Nitinol Alloys", a large number of animal experiments have shown that including inhalation of animals, instillation into the trachea, and the injection of nickel compounds in various parts, Both successfully induced malignant tumors. Although the mechanism is not clear, the evidence suggests that it is related to free radical production.

The 3D printed micro-robot is covered with nickel and titanium to increase magnetic and biocompatibility. The paper shows that although titanium-nickel alloy has strong corrosion resistance and wear resistance, corrosion will exist to varying degrees. As a result, nickel precipitation increases, and long-term existence is bound to cause cancer.

"There is still a long way to go for clinical treatment, especially in terms of safety evaluation. Further research and verification are needed." Yang Guanghua said that "getting in and out" is able to avoid the body. A method of damage. For example, the carrier material in the nano-gun "bullet" uses a self-degradable nano-material to solve this problem.

In addition, in order to prove that manipulation in the blood vessels is feasible, the research team also used microfluidic chips to simulate a more complex vascular structure, demonstrating that micro-robots can transport cells in such a system. However, it is not known how much the real human environment and the simulated environment are different. At a Xiangshan Science Conference, some academicians said that there may be undetected vibrations in the blood flow of the human body. Whether the performance of micro-robots in "exercise" can be consistent with "actual combat" remains to be further tested. In the real environment of the body, micro-robots may face serious challenges beyond imagination.

"The magnetic force that controls the movement of micro-robots is very weak, and the blood pressure in the human body is huge. Therefore, it is a challenge to accurately and effectively operate the robot to achieve the medically demanding standards." Yang Guanghua said that clinical application It is required to have stable effects and high safety. To achieve "reaching standards", it may be necessary to carry out in-depth research involving cross-disciplines such as fluid motion models.

Source: Technology Daily

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