The development of tumors is inseparable from the supply of nutrients from blood vessels. Therefore, blockage of blood vessels is expected to end the allometric growth of malignant tumors, and will also significantly reduce the risk of tumor cells metastasizing to other sites. Starting from this basic idea, the medical community has developed a method of vascular embolization in the treatment of tumors in recent years. It aims to cause ischemic necrosis of the supply artery and microvessels of solid tumors through embolizing agents, and then achieve the goal of starving the tumor. From the perspective of the development trend of modern medicine, vascular embolization interventional therapy has the advantages of minimally invasive, safe, low toxic and side effects, reproducible, and definite efficacy, and can provide the best benefit plan for tumor patients, especially those who have lost the opportunity for surgical resection .
In fact, until now, vascular embolization, especially hepatic arterial chemoembolization, has become one of the preferred treatments for liver cancer. Due to the significant clinical value of tumor embolization agents, countries in the world, especially in Europe and the United States, have been intensifying research and development, constantly innovating, and many products have been approved by the US FDA and European clinical applications. For China, the most clinically used embolizing agent products are basically imported from Europe and the United States. The tumor embolization treatment field is facing the unfavorable situation of shortage of resources, high cost, and many imitation products. It needs to be changed urgently. Undoubtedly, in this medical practice, the choice of embolizing agent plays an important role in ensuring the therapeutic effect and patient survival rate.
Commonly used vascular embolization materials generally include solid embolization agents and liquid embolization agents, where solid embolization agents include blood clots, granular embolization agents, gelatin sponges, gel microspheres, drug-loaded microspheres, stainless steel coils, etc., which require special catheters Delivery to blood vessels; liquid embolization agents include anhydrous alcohol, sodium cod liver oleate, iodized oil, and Onyx liquid embolization system, etc., which can be delivered to blood vessels through ordinary catheters, but the operation is complicated, the preparation is difficult, and it is not easy to remove after use. It can be said that since the development at home and abroad, embolizing agents with good maneuverability, high-efficiency embolism and high-definition contrast effects are all very lacking.
Around 2013, the Liu Jing laboratory of the School of Medicine of Tsinghua University first proposed a subversive liquid metal vascular embolization method for treating tumors and angiography technology. The principle is that the metal fluid embolization agent is directly injected into a specific blood vessel location by means of an injection device. In order to implement precise embolization of the target tumor. With the help of medical imaging systems such as CT, X-ray, and DSA, liquid metal embolization agents can achieve high-definition contrast, and are not easily washed away by blood flow. They can fully block the entire blood vessel cross section, have good controllability, and have no obvious toxic and side effects. , It is not easy to mistakenly embolize, and the dosage is standard. Most of these advantages are not easy to have with traditional embolizing agents. This kind of surgery is relatively easy to implement, and the liquid metal embolization agent can be infused into a specific blood vessel site through the microsurgical process, and then the tumor apoptosis is observed. The whole process is different from classic tumor therapy such as surgical resection, radiotherapy, and chemotherapy Such a violent operation is equivalent to fighting a tumor battle without smoke. Once the new method was proposed, it triggered a series of reports on international scientific news and professional websites. However, the performance of pure liquid metals or their alloys is still limited and needs to be improved.
Recently, on the basis of years of continuous research, Liu Jing's group reported a new generation of functional compound tumor embolism agent: liquid metal / calcium alginate (LM / CA) hydrogel, which is flexible and easy to operate, injectable and It can be developed and loaded with drugs, and can be made into tumor preparations with specific functions as required. In the study, the LM-liquid metal was introduced into small particles by ultrasound, which were evenly dispersed in the aqueous solution of sodium alginate (SA-sodium alginate). Combined with the calcium ion solution, it can quickly form a solid state in situ Liquid metal / calcium alginate (CA-calcium alginate) hydrogel.
A large number of principle tests have shown that this hydrogel has a high degree of vascular compliance, good hydrophilicity, uniform structure, and good plasticity. After injection into the body, the combination with the blood vessel is tight and reliable, and it can be used as a high-performance vascular embolization agent to block blood vessels. Carry out tumor treatment for tumor and surrounding tissue ischemic necrosis. The outstanding advantage of LM / CA hydrogel is that it has rapid curing ability, which can achieve rapid embolization in a fixed point in the blood vessel; secondly, because the liquid metal has excellent X-ray developing ability, the hydrogel has visibility in the blood vessel, Greatly improve the precise positioning of materials during the surgical operation; due to the introduction of the idea of multi-functional composite materials, the new embolization preparations still have a lot of room for further expansion of performance. Prior to this, most of the widely used clinical embolization agents had relatively weak imaging functions, which severely restricted the efficient implementation of the corresponding surgery.
This achievement was published online in the internationally renowned journal Small with the title of "Injectable and Radiopaque Liquid Metal / Calcium Alginate Hydrogels for Endovascular Embolization and Tumor Embolotherapy". Tsinghua University School of Medicine 2016 doctoral student Linlin Lin, 2017 doctoral student Duan Minghui Teacher Xie Zhongchen from the Center is the co-first author of this article, Liu Jing, a professor in the Department of Biomedical Engineering of Tsinghua University School of Medicine, and a dual-researched researcher at the Institute of Physical and Chemical Technology, Chinese Academy of Sciences, is the corresponding author.
1. Injectability and plasticity of materials
The LM / CA hydrogel has a low viscosity before curing, has excellent fluidity and injectability, and greatly simplifies the injection operation of the material.
2. Excellent biocompatibility and visibility
Experimental studies in vivo and in animals show that LM / CA hydrogel has excellent biocompatibility. Within four weeks, the liver and kidney functions of the mice were not abnormal, and the results of in vitro hemolysis and coagulation tests were not abnormal. At the same time, the LM / CA hydrogel has X-ray and CT developability, which will provide strong support and help for the positioning of the embolization material during the surgical operation.
3. Simple operation, precise positioning and rapid embolization
The LM / CA hydrogel can be injected into the blood vessel at a fixed point using a disposable syringe, which can accurately locate the material position under the guidance of X-ray or DSA. LM / CA hydrogel has excellent vascular embolization effect, and the tumor embolization treatment effect is remarkable.