A variety of micro and nano drug carrier robots rely on self-propulsion movements to cross the barrier of multiple biological barriers to send drugs to the bottom of the eyeball or deep in the brain tissue, so that the thorny medical problems such as glaucoma, epilepsy, glioblastoma, stroke hemiplegia and so on can be solved. With the deepening of research, researchers at the Micro and NanoTechnology Research Center of Harbin Institute of Technology are turning these seemingly sci-fi scenarios into reality step by step.
The reporter learned from Harbin Institute of Technology (hereinafter referred to as Harbin Institute of Technology) on April 19 that the research paper "Double Response Biological Hybrid Neutrophil Robot for Active Targeted Delivery" completed by professors He Qiang and Wu Zhiguang of the university's micro and nanotechnology research center was recently published online in the international journal "Scientific Robot". Prior to this, the results of a series of scientific research projects of swimming micro-nano robots independently developed by the research group have also been published in more than 20 international journals such as "German Applied Chemistry", "Advanced Functional Materials", "MIT Science and Technology Review", "Journal of the American Chemical Society", etc., with a maximum impact factor of 27.4 points, laying the leading position of Chinese scientists in the field of medical nanorobot research at home and abroad.
The construction of active drug transportation channels has become a hot spot in the industry
According to reports, conventional drug delivery, such as injection, medicine, infusion, etc., is based on the spread of drug molecules or carriers in the blood, resulting in inefficient delivery. Some scholars have made statistics on drug delivery in the past 30 years, and found that after about 12 hours of traditional delivery, less than 1% of the drugs reached the target location. This means that the vast majority of medications have been lost on the road. Therefore, the construction of a new type of drug active transportation channel has become a research hotspot in the industry.
In 1966, a foreign film called "The Fantastic Journey" depicted a medical scientist suffering from a serious illness, and in order to survive, he had to make a risky decision to reduce five of his colleagues to nano-size, inject them into his body, and let them "swim" directly to the lesion area to treat him. Inspired by this illusory story, researchers have been dreaming of creating and inventing a nano-robot that can swim autonomously, load drugs on the robot, let the robot carry out "free swimming" in the human body, and finally go directly to the lesion site to exert its medicinal effect.
Looking back in history, the first to propose the idea of micro-nano machines was Nobel Prize winner and theoretical physicist Richard Feynman. In 1959, he envisioned building micro-nano-scale micro-nano machines from atoms or molecules. In a lecture titled "There is a lot of space at the bottom of matter," Feynman described that in the future it is possible for humans to build a molecule-sized miniature machine that can construct matter in a very small space using molecules or even individual atoms as building blocks. This is undoubtedly the ideal shore that chemists and biologists intend to achieve.
Happily, since 2004, a variety of chemical and external physics (such as photoelectromagnetic heat)-driven swimming micro-nano robots have emerged in the industry, which can swim efficiently in water. However, the human internal environment is very complex, especially in the body, there are also a variety of biological barriers such as blood-brain barriers and blood-eye barriers, which protect the human body from the invasion of foreign bacteria and viruses at the same time, but also prevent these robots from accurately delivering drugs to the patient area.
Atomically assembled "swimmers" can fool the immune system
Professor Wu Zhiguang, director of the Micro-nano Actuator and Microsystem Branch of the China Society of Micro and Nanotechnology and doctoral supervisor of HIT, said that the early swimming micro-nano robots were basically composed of components such as micro-electromechanical systems, and their own materials were mainly metals, metal oxides and artificial polymers. After such micro-nano robots enter the body, they cannot be degraded at first, so they have great danger; secondly, these metals and metal polymers are exogenous substances of the human body, with poor biocompatibility, once they enter the body, they will trigger the "alarm" of the immune system, and then be surrounded by immune cells, resulting in "death before the teacher", before reaching the lesion, it may have been "strangled" by the human immune system. To this end, Wu Zhiguang's team used their brains to disguise micro-nano robots as natural cells for the first time, deceiving the identification of the immune system.
In addition, "the first thing to be solved in the development of micro-nano-size robots is the driving problem, and many driving methods in the macroscopic world are difficult to achieve in the microscopic world." Wu Zhiguang said, "If a person lies in a bathtub full of water, he can float up." But if you condense people into nanoscales, water feels like a very thick syrup that makes people unable to move. ”
Scientists have found that there are many micro- and nano-scale things in nature that can travel at will, such as molecular motors, biological motors, bacteria, sperm, etc., which can move forward with the help of asymmetrical regional fluid fields generated during oscillation. Based on this principle, the researchers designed a series of swimming micro-nano robots and introduced them into the field of biomedical research. As early as 2010, He Qiang set up the first domestic swimming nanorobot research and development team at HIT, under his organization, Wu Zhiguang and his colleagues applied chemical methods to assemble atoms into micro-nano structures for the first time, and successfully performed controlled swimming under the chemical field or external light and magnetic field, and even directly guided to the target cell.
Clinical translational application depends on two important links
"However, if these micro-nano robots want to be transformed and applied in the clinic in the future, there are two important links that cannot be avoided." Wu Zhiguang explained that first of all, micro-nano robots must be able to move in complex human environments. "One is to be able to actively break the cell membrane, the second is to be able to operate in the blood, and the third is to be able to move in biological fluids such as vitreous bodies in the eyes and mucus of the gastrointestinal tract." When swimming against the blood flow, the flow rate has a greater impact on micro-nano robots. The research team found that there are many animals and microorganisms in nature that survive in fluid environments, and in order to better adapt to the fluid environment, these beings often choose to move close to the substrate. Inspired by this, He Qiang's team developed two kinds of swimming micro-nano robots that can move along the substrate, as well as a robot with a smaller size than the pore size of the biohydrogel, which can freely shuttle through the vitreous of the eye, and the accuracy of its movement direction is within 9 square millimeters, reaching a level that is unattainable by conventional ophthalmic drug carriers.
The second is the imaging and control problem of swimming micro-nano robots. Wu Zhiguang explains: "The size of the nanorobot is small, generally much lower than the conventional imaging resolution, and the contrast with biological tissue is insufficient. To this end, the research team wrapped the robot to increase its appearance size; at the same time, with the help of the action separation method, extracted and mastered the action behavior completely from the swimming micro-nano robot, distinguished it from the biological tissue, and finally completed the real-time imaging and accurate control of the mobile micro-nano robot, laying a solid foundation for the application of the mobile micro-nano robot in the biomedical field.
Among the important achievements that have been made, He Qiang's team has for the first time developed a robot that effectively and stably carries anti-cancer drugs such as paclitaxel, relying on the self-developed control system, breaking through the blood-brain barrier and hematoma barrier, sending drugs into the depths of brain lesions, significantly enhancing the concentration and targeting efficiency of paclitaxel, and making the stubborn "fortress" of glioblastoma disintegrate from the inside. The international cooperation project "A group of smooth miniature spiral robots through the vitreous body of the eye" participated by Wu Zhiguang, and the robot "small tadpole" made of nano-scale 3D printing technology successfully "swam" into the eyes of experimental animals, and in less than 30 minutes, it has "landed on the beach" to the retina, which is 10 times faster than the speed of similar size drug particles through the eye, opening up a new path for the treatment of glaucoma, macular edema and cataracts in the future. Many well-known academic journals such as Science and Nature have reported their research progress and given high praise.
Going forward, nanoscale technology will no longer be just the cool technology that superheroes in Hollywood blockbusters have, it will become a part of human life. American futurist and Google engineering director Ray Kurzweir predicted that in the future, medical nanorobots are expected to connect the human brain and the cloud brain (cloud computing system) to improve human intelligence and prolong human life. In 2030, swimming nanobots will settle in the human body, with blood circulation throughout the human body, laying the groundwork for precision medicine.
"The prospect is bright, the future can be expected!" He Qiang said frankly that the road to exploration in the future is still very difficult and long, after all, biological medical devices or drugs must undergo a long period of multi-stage clinical experiments and observations to blossom and bear fruit. (Li Liyun)
Source: Science and Technology Daily