Put on the nano "coat" of medication to directly reach the lesion

Exosomes efficiently load drug molecules and achieve targeted delivery. (Courtesy of Shenzhen Advanced Institute)Editor's noteIn recent years, the Chinese Academy of Sciences Shenzhen Advanced Technology Research Institute (hereinafter referred to as "Shenzhen Advanced Technology Research Institute") has focused on health and medicine, robotics, new energy and new materials, big data and smart city and other fields, in high-end medical imaging, low-cost health, medical robots and functional rehabilitation technology, urban big data computing, brain science, advanced electronic packaging materials, tumor precision treatment technology Major technological achievements in the fields of synthetic biological devices are constantly emerging

Exosomes efficiently load drug molecules and achieve targeted delivery. (Courtesy of Shenzhen Advanced Institute)

Editor's note

In recent years, the Chinese Academy of Sciences Shenzhen Advanced Technology Research Institute (hereinafter referred to as "Shenzhen Advanced Technology Research Institute") has focused on health and medicine, robotics, new energy and new materials, big data and smart city and other fields, in high-end medical imaging, low-cost health, medical robots and functional rehabilitation technology, urban big data computing, brain science, advanced electronic packaging materials, tumor precision treatment technology Major technological achievements in the fields of synthetic biological devices are constantly emerging. To showcase the significant scientific and technological achievements of Shenzhen Advanced Institute, Shenzhen Business Daily has launched a "Achievements Come" column today, reporting a series of scientific and technological innovation achievements of Shenzhen Advanced Institute.

Shenzhen News Network, October 24, 2023(Chen Xiaohui, Chief Reporter of Shenzhen Business Daily) In the science fiction film "Fantastic Journey", in order to save a scientist whose cerebral blood vessels were damaged, five doctors were reduced to several million parts in size and injected into the scientist's body for vascular surgery.

This precise "navigation" to the lesion is now being achieved in the pharmaceutical field, utilizing nano drug carrier technology.

The biological structure of exosomes.

With the development of the biopharmaceutical industry and the rapid iteration of innovative drugs, the problem of insufficient utilization of drug components in the human body has always existed. Nanocarrier technology helps drug molecules enter the body and be transported to accurate treatment locations in an accurate manner at an accurate time, improving the efficiency of drug utilization in the human body. To carry drugs on drug carriers, a series of emerging nanotechnology systems are needed Yang Hui, director of the Intelligent Sensing Center of the Institute of Biomedical and Health Engineering of the Chinese Academy of Sciences Shenzhen Institute of Advanced Technology (hereinafter referred to as "Shenzhen Institute of Advanced Technology"), said that at present she is leading her team to engage in the research and development of new nano engineering and micro/nano flow control technology. It is expected that drugs will be carried into clinical trials within a year or two to promote the research, development and large-scale production of new nano drugs.

Drug carrier technology determines whether drug molecules can become drugs

Currently, therapeutic drug molecules mostly appear in the form of biological molecules such as antibodies or nucleic acids, such as nucleic acid drugs, which are widely recognized as "sharp tools" for combating stubborn diseases such as tumors and Alzheimer's disease. Based on a wide range of application scenarios and mature technological systems, many pharmaceutical companies have flocked to the nucleic acid drug research and development track. However, the development of nucleic acid drugs still faces many problems, with drug delivery technology being the most concerned.

It is understood that nucleic acid drugs usually face three major difficulties in entering the body: firstly, the molecular weight and negative charge of nucleic acids prevent them from freely passing through biofilms; Secondly, ribonucleic acid (RNA) is easily degraded by enzymes in plasma and tissues, quickly cleared by the liver and kidneys, and recognized by the immune system; The third reason is that after entering the cell, the "card" cannot function in the endosomes. To overcome difficulties, drug delivery technology is needed.

Without the use of drug delivery technology, general drug molecules entering the body will undergo liver and kidney metabolism, resulting in minimal therapeutic effect. If the dosage is too large, it may also cause damage to the digestive organs, "Yang Hui said, The drug delivery system is a technical system that comprehensively regulates the distribution of drugs in the human body in terms of space, time, and dosage. It is equivalent to putting a 'coat' on drug molecules, allowing them to enter the body and deliver an appropriate amount of drug molecules to the correct position at the appropriate time, and complete the expected release, thereby increasing the utilization efficiency of drug molecules, improving efficacy, and reducing toxic side effects

Moreover, drug delivery will greatly shorten the drug development cycle. We all know that drug development has a long cycle and high investment, requiring a certain validation cycle from drug discovery to final patient application. However, using drug delivery technology can directly 'tailor the drug to the case', greatly shortening the validation cycle, reducing capital costs, and improving the efficiency of drug development, "said Yang Hui.

Innovative drug delivery and production methods

So, how does medication achieve precise delivery? What are the methods of drug delivery?

Lipid nanoparticles are one of the most widely used delivery systems in the research and application of nucleic acid drugs, "Yang Hui told reporters. Lipid nanoparticles are commonly referred to as LNP technology in the industry, equivalent to the" coat "of nucleic acid drug molecules, tightly encapsulating nucleic acid. After these lipid nanoparticles loaded with drug molecules enter the human body, they will have a protective effect, preventing the drug molecules from being digested and absorbed by enzymes in the body.

At the same time, the components rich in these lipid nanoparticles themselves are the main components of the cell membrane, so they have a natural affinity for the cell membrane and can fuse with the cell membrane to release the messenger RNA molecules carried into the cell for drug action.

In addition to lipid nanoparticles, exosomes delivery systems are also one of the main delivery methods, which is also one of the main technologies studied by Yang Hui's team. According to Yang Hui, exosomes are membranous vesicles released into the extracellular matrix by the fusion of intracellular vesicles and cell membranes. Market research company GrandViewResearch predicts that by 2030, as a drug delivery system alone, the exosomes therapy market size will reach $2.28 billion.

So, how were these delivery "coats" manufactured? This cannot be achieved without the production tools of drug delivery technology.

We have innovated the production method of drug delivery technology and developed exosomes nanoengineering technology. This technology achieves precise and reliable micro/nano scale biological/biochemical reactions, and can load exogenous substances (therapeutic drugs) into exosomes with high throughput and efficiency, for the discovery and development of breakthrough drug delivery vehicles, treatment and diagnostic products. "Yang Hui introduced that the team pioneered the ExoNP platform, On the basis of not damaging exosomes and loaded substances, the ExoNP platform can meet the efficient and high-throughput loading and delivery needs of different types of drug molecules (nucleic acids, proteins, peptides, and small molecules, etc.) on exosomes, and can be applied in fields such as tumors, autoimmune diseases, neurodegenerative diseases, and infectious diseases.

Yang Hui stated that the team has also innovatively created a data mining platform for key extracellular membrane proteins and a large-scale production solution for extracellular drug formulations. In the future, they will continue to provide disruptive technologies from chip laboratories to large-scale production of drug GMP, assisting in the research and production of nanomedicines, providing new precise targeted drug carriers for new drugs such as chemical drugs, nucleic acid drugs, protein drugs, and achieving a complete and scalable process flow, Accelerate the large-scale production of drugs.

Within one or two years, drugs will be loaded into clinical trials

At present, we have collaborated with some pharmaceutical companies, whether in the fields of nucleic acid drugs, protein drugs, or chemical drugs. It is expected that drugs carried by our nanocarrier technology will enter clinical trials within one to two years. "Yang Hui said of the progress in the transformation of team research achievements. In terms of instrument development as a drug development tool, she revealed that some "tools" will also receive medical device registration certificates next year.

Yang Hui stated that Zhongke Baicheng not only provides drug delivery solutions and technologies, but also has the ability to produce "outerwear". It will provide solutions throughout the entire process from carrying solutions, drug delivery technology research and development, clinical trials, to large-scale production, aiming to become an excellent partner in global pharmaceutical and biotechnology. Source: Shenzhen Business Daily

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