Nano "rocket" escorts genetic drugs to the focus
2021-12-29
The "launch vehicle" is ready to go. It will pass through many obstacles and accurately help the "missile" hit the "bull's-eye"... Is this the scene in the launch site? No, it all happens at the micro level. This "rocket" with only about 100 nm is a "polymer gene / drug carrier" constructed by Tian Huayu, a researcher of Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Recently, this research achievement won the first prize of Jilin Natural Science Award in 2021. In recent years, researchers have been trying to build efficient, safe and low-cost polymer carriers to plug in the wings of gene therapy, a high-profile medical technology. Academician Chen Xuesi of Changchun Institute of Applied Chemistry, Chinese Academy of Sciences recognized the importance and urgency of developing high-performance polymer gene vectors as early as 20 years ago. He once said: "on the one hand, we should do profound basic research, analyze basic scientific problems, and know why, which is the premise to ensure that our research can be at the international leading level. On the other hand, we should explore problems in actual needs and strive to promote the industrialization and commercialization of polymer gene vectors." The achievement of this award is the reward of the researchers of the Institute for 20 years. Gene therapy faces the problem of "ammunition" transportation The essence of gene therapy is to achieve the purpose of treatment by regulating genes. Gene therapy usually needs to construct therapeutic genes, and then send these genetic materials into genetically abnormal cells to repair abnormal genes and produce beneficial proteins. Since the birth of gene therapy technology in the 1970s, it has been regarded as a revolution in the field of medicine and pharmacy. It is expected to cure all kinds of diseases caused by gene defects or abnormalities. After years of technical iteration, renewal and accumulation, gene therapy has made rapid progress. A number of breakthrough treatment methods and gene therapy drugs have come out one after another, and a series of clinical results have been achieved. Because of its excellent performance, gene therapy has attracted the attention of scientists all over the world. In the 1990s, scientists from various countries successively carried out relevant research: in 1992, Italian scientists successfully modified hematopoietic stem cells with retrovirus for the first time. In the following 20 years, positive results have been achieved in gene therapy of hemophilia, solid tumor and leukemia. By 2017, The United States approved the second therapy based on modifying patients' autoimmune cells to treat patients with specific lymphatic cancer. Gene therapy has once again set off a research upsurge. In recent years, many governments in China have also taken gene therapy as the key core technology for the future scientific and technological innovation and development in their scientific and technological development plans. However, such a magical gene therapy faces a key problem: how to transport genes or drugs to the target. For example, a powerful weapon lying on a launcher is not lethal. Take gene therapy tumor as an example. If you want the "ammunition" to work, you must have a "carrier rocket" to send it to its destination. "The human environment is more complex than the atmosphere. It is very difficult to transport the modified genes to the cells in need of treatment and avoid normal cells at the same time." Tian Huayu told Science and technology daily. Polymer carrier ensures transportation efficiency and safety For gene therapy, the ideal vector should not only carry a sufficient number of gene or drug "ammunition", but also have no toxicity and pathogenicity to human body, so as to ensure safety; It should not only be strong enough to protect the "ammunition" from nucleases, but also accurately find tumor cells and enter the nucleus. Polymer carriers are generally cationic polymers, which have the advantages of safety, low toxicity, easy functionalization and mass production. However, their low transfection efficiency and lack of intelligent response are a difficult problem for researchers all over the world. Tian Huayu led researchers to adopt the strategy of "introducing multiple interactions and synergy", graft p-toluenesulfonyl protected arginine on polylysine to obtain high-performance polymer carrier, and make electrostatic interaction, hydrogen bond interaction and hydrophobic interaction cooperate, so that the driving force of carrier entering cells changes from single to multiple, It greatly increases the efficiency of carrier entering cells. "This is like the upgrading of rockets. Previously, it was only a single-stage rocket. Now we connect or bundle multiple rocket engines in series, which greatly increases the power of the rocket." Tian Huayu said that the polymer carrier can self assemble into nanoparticles. The transmission electron microscope results show that the assembly of nanoparticles is spherical, with an average size of about 75 nm. More interestingly, researchers also designed a "invisibility cloak" for this nano "rocket". Tian Huayu explained that this is because the requirements of the circulatory system and the tumor site for the physical and chemical properties of the gene carrier are contradictory when the polymer carrier transmits gene material to the tumor tissue in vivo. "The cationic polymer itself has a positive charge. We hope to use the excess positive charge to help it enter the tumor cells, but during transportation, it is easy to interact with negative proteins in body fluid or with non-target tissue cells, resulting in nonspecific phagocytosis, which seriously affects the transmission efficiency of complex nanoparticles to the target tissue." Tian Huayu said. Therefore, researchers skillfully wrapped the "rocket" tightly with dialdehyde polyethylene glycol and compressed its volume, so that it can deceive the negative proteins in the body and enter tumor cells efficiently. After reaching the destination, the "invisibility cloak" will be "removed" in the special acidic environment of tumor cells. The carrier is upgraded from single function to multi-function From the practical effect, this new polymer carrier realizes the efficient transmission of gene materials in vivo, and has achieved exciting results in anti-tumor therapy. The experimental results showed that the endocytosis efficiency and tumor growth inhibition rate of tumor cells were significantly improved by this method. Moreover, researchers also introduced detection and combined treatment units into the carrier to build a multi-functional carrier, which improved the ability of real-time monitoring and treatment of diseases. "The polymer carrier system we constructed has the ability of gene and photoacoustic dual-mode imaging and the function of gene and photothermal combined therapy. The above characteristics upgrade the polymer carrier from single function to multi-function, and has the ability to diagnose and treat tumor tissues as a whole and double kill." Tian Huayu said. Polymer carrier combined with shielding system has become a universal carrier platform after carrying genetic materials, proteins and chemotherapeutic drugs. Using this platform, Tian Huayu and others further constructed two nano drug delivery systems based on the response of tumor acidic microenvironment - chemotherapy drug loading system and gene loading system, and then developed a new immune cocktail therapy. This therapy has shown excellent therapeutic efficacy in several tumor models. Localization of gene transfection reagents to break foreign monopoly Related links Since Chen Xuesi laid out an efficient gene therapy vector 20 years ago, industrialization and commercialization is one of the main objectives of this technology. Although it will take some time for gene vectors to move towards clinical treatment, the time is ripe for the industrialization of gene transfection reagents. As a key link of gene therapy, the core technology of gene transfection reagent has always been monopolized by foreign companies. In view of this, with the encouragement and leadership of Chen Xuesi and the strong support of the Ministry of science and technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Department of science and technology of Jilin Province, researcher Tian Huayu has been engaged in the research and development of gene transfection reagents for 20 years, making innovations and overcoming difficulties on the basis of previous studies, China has completely got rid of the difficult dilemma of being controlled by others in this field. "A breakthrough has been made in domestic gene transfection reagents, which has changed the current situation of China's dependence on imports of gene transfection reagents." Tian Huayu said. At present, the research team has successfully developed three varieties of gene transfection reagents and is gradually expanding the market. At present, they have been used in more than 50 universities, hospitals and scientific research institutions. (outlook new era)
Edit：Yuanqi Tang Responsible editor：Xiao Yu
Source：
Special statement: if the pictures and texts reproduced or quoted on this site infringe your legitimate rights and interests, please contact this site, and this site will correct and delete them in time. For copyright issues and website cooperation, please contact through outlook new era email：lwxsd@liaowanghn.com
Recommended Reading Change it 
Home
