Freeze-drying is a common way to preserve fresh fruits and vegetables on the market, through the treatment method of low temperature and then vacuum, the water in the vegetables and fruits is directly sublimated from ice to water vapor, so as to achieve the effect of dehydration and preservation. Freeze-drying technology can maintain the color and flavor of food, and can retain most of the nutrients in the food, won the love of many consumers.
Gu Zhen's scientific research team.
So can people also freeze-dry some body tissues, maintain their internal active ingredients and structure, give full play to their own characteristics as an active material, and use them in the field of biomedicine?
A few days ago, the team of Professor Gu Zhen and Li Hongjun of the School of Pharmacy of Zhejiang University and the Jinhua Research Institute of Zhejiang University joined the team of Chief Physician Zhao Peng and Chief Physician Chen Dong of the First Affiliated Hospital of Zhejiang University School of MedicineFor the first time in the world, it is proposed to use freeze-drying technology to turn body tissues into active biomaterials, and then load drugs to exert efficacy. In this study, the lymph nodes removed from the body were freeze-dried, and their porous structure and a large number of active ingredients were effectively retained, which were used as a medium for storing and delivering anti-tumor cell drugs to achieve the purpose of being more powerful and longer-lastingIn animal models, it has been verified that this technique can effectively inhibit the postoperative development of malignant tumors.
The results were published on March 6 in the internationally renowned journal Nature Materials.
Schematic diagram of lyophilized lymph node delivery of CAR T cells** tumor.
Use local materials to kill two birds with one stone
In recent years, the use of cell drugs as tumor targeting** has been on the rise. For example, by adding a "probe" to immune T cells, chimeric antigen receptor T cells (also known as CART cells) that can accurately identify and target tumor cells are synthesized, which has been used in clinical treatment of hematological tumors and achieved significant efficacy.
However, how CART cells can function in solid tumor sites in a lasting and efficient manner has always been a long-standing problem. Scientists have tried to "build" all sorts of things near tumorsA "bunker" that can be loaded with CART cellsIt is often hindered by factors such as physical barriers and immunosuppressive environment, as well as the immune rejection reaction faced by the materials used to build the "bunker", which affect the efficacy.
We're thinkingIs it possible to use some body tissue in the body to load CART cells? Gu Zhen introduced, "We first thought of the lymph nodes that often need to be dissected during tumor surgery, so that local materials can be used to avoid the rejection problem caused by exogenous carriers." ”
When performing malignant tumor resection surgery, it is often necessary to dissect the lymph nodes in the area, and determine whether these lymph nodes have metastasis through pathological testing, so as to accurately guide the follow-up ** after surgery. And these removed lymph nodes themselves are also very important immune organs in the human body, for exampleThe "arsenal" of the immune systemIt is naturally a suitable place for T cells to survive, train and expand.
"Can the advantages of the two be further superimposed, not only allowing lymph nodes to protect CART cells, but also promoting the anti-tumor activity of cells, so as to achieve two birds with one stone? ”Gu Zhen further introduced the research ideas.
Since 2021, researchers at Zhejiang University have been working how to make the "arsenal" a "bunker".
Freeze-dried "lock freshness", with many advantages and good effect
How do I make more room for lymph nodes to load CART cells? Gu Zhen's team, which has long-term scientific research practice in the field of medical cryotechnology, creatively proposed to carry out lymph node tissueFreeze dryingideas.
During lyophilization, the water in the lymph nodes is frozen into ice and quickly sublimated, creating more cavities to house T cells. The lyophilized lymph node tissue has strong water absorption and can quickly absorb CART cells.
Lyophilized lymph node scanning electron microscopy** (left, where the purple spheroids are CART cells) and fluorescence imaging** (right, where the green spheroids are CART cells) loaded with CAR-T cells
How effective is lyophilized lymph nodes?
Through comparative experiments, the researchers found that the CART cells loaded in the lyophilized lymph nodes were co-cultured with tumor cells for 3 days, and the expansion of CART cells was artificially prepared as a gel carrier3.5 times。After 7 days of culture, the lyophilized lymph node experimental group was able to differentiate T cells into more memory phenotypes, which was indicativeThe use of lyophilized lymph node carriers can make CART** more effective and longer-lasting.
InTumor model studies of human tumor cell lines and patient tumor tissues**lyophilized lymph nodes have significant synergistic effect on CART cells. "The tumor inhibition effect, the number of intratumoral activated CART cells, and the amount of killer factors produced by lyophilized lymph nodes loaded with CART cells** were significantly better than those of the same dose of CART loaded on gel carriers. Li Hongjun said.
Zhao Peng said: "Lyophilization has the function of 'locking freshness', and the lyophilized lymph nodes are returnedThe abundant cytokines, chemokines, and ligands are retained, which plays an important role in maintaining the activity and function of CART cells. ”
Clinic-oriented, clinical-serving
Researchers at Zhejiang University are looking forward to lyophilized lymph node technology.
In the future, lyophilization of lymph nodes and loading of cellular drugs can be completed in just a few hours, and even within the time of a surgical operation, the lyophilized lymph nodes loaded with drugs can be buried back in the cavity after tumor resection, as a cart cell reservoir, a continuous release of drugs to remove local residual microscopic tumors and inhibit the ** after surgery.
Lymph nodes are lyophilized.
This study showed a strong ...Characteristics of a combination of basic and clinical。Most of our team is dedicated to clinical practice, and we usually lead students to observe clinician ward rounds and surgeries. Gu Zhen said"The team is working together to refine some clinical research protocols so that it can help patients as soon as possible. ”
Not only that, lyophilized tissue technology can not only be used to modify lymph nodes and load CART cells, but also provide a new idea for future scientific research. Chen Dong said"Freeze-drying technology can also be extended to other tissues and organs to prepare biomaterials with special properties for use in the biomedical field. ”
As the anonymous reviewer commented, this work is highly innovative and has the potential to meet important clinical needs in oncology.
The first authors of the study were Shi Jiaqi, a Ph.D. student at the School of Pharmacy, Zhejiang University, Wei Wu, a Ph.D. student at the School of Medicine, and Dong Chen, the First Affiliated Hospital of Zhejiang University School of Medicine.
Text reporter: Li Junyuan, student reporter group of Zhejiang University Rong ** Center, Ke Yineng audio and video production: Yang Luoluo, Liu Yuxiang, just be happy|Research**Courtesy of the team interviewed.
Today's editor: Li Junyuan, student journalist group of Zhejiang University Financial ** Center.
Editor in charge: Tan Shuai.
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