With the rapid development of nanotechnology, it is cross-integrated with various disciplines, and new research fields and discipline growth points are continuously produced. Especially in recent decades, nanotechnology has rapidly penetrated into the field of biomedicine, forming a brand-new research field-bio-nanomedicine. It applies nanotechnology to the field of biomedicine, involving materials, physics, chemistry, biology, medicine and quantum science and many other disciplines, forming a comprehensive interdisciplinary.
Bio-nanomedicine has become an important direction for the development of nanotechnology, and has quickly become the frontier and hot spot of the development of biotechnology in various countries in the world, with a wide range of applications and clear industrialization prospects. This rapidly developing new research field will provide new technologies and methods for modern biomedical research, reveal new perspectives for important biomedical issues at the nanometer scale, and reveal relevant new principles and possible practical applications.
At present, the field of bio-nanomedicine covers many aspects. The main research directions include nano-biological effects and safety, nano-toxicology, biosensing, tissue engineering, medical imaging, drug delivery, diagnosis and treatment of diseases (especially tumors), etc.
In recent years, Chinese researchers have firmly grasped the opportunities of the booming development of bio-nanomedicine, constantly challenged themselves, and high-level scientific research results have emerged one after another. They have made many new breakthroughs in the field of bionanomedicine and have occupied an important position in the field of international bionanomedicine. Based on the discussion and consensus of the 384th Young Scientist Forum of the Chinese Association for Science and Technology-Bio-Nanomedicine Young Scientists Forum, this article reviews cutting-edge research in the field of bio-nanomedicine, and looks forward to the opportunities, challenges and developments in this field.
Perfect combination of "self" and "artificial"

Nanomaterials are easily recognized and eliminated by the body‘s immune system, which greatly limits their applications. Inspired by nature, people carry out biomimetic structural designs that combine the "self" nature of organisms with the advantages of "artificial" nanomaterials.
The team led by Yan Xiyun, a researcher at the Institute of Biophysics of the Chinese Academy of Sciences and an academician of the Chinese Academy of Sciences, has conducted research on precision tumor treatment for many years, discovered and defined nanoenzymes, and established nanoenzyme standards. On this basis, they analyzed the binding capacity of natural enzymes and substrates, optimized the bionic design by simulating the active center, and improved the catalytic efficiency of iron-based nanozymes.
At the same time, based on the experience gained, creatively designed nanomaterials from "no enzyme activity" to "enzyme activity", and completed the major strategic transformation from "bionic structure optimization" to "bionic structure design". Fan Kelong, a young scientist in Yan Xiyun‘s research group, has systematically sorted out the past and present of nanoenzyme research as a window connecting inorganic and biological. For the first time, they used ferritin to target brain endothelial cells and intracellular sublocalization properties to achieve the regulation of iron-based nanozymes in the brain to perform catalase activity, combined with ferritin to regulate the polarization of liver macrophages Characteristics, to achieve effective treatment of falciparum malaria model.
The research team of Professor Liu Gang of Xiamen University has developed a biomimetic vesicle structure whose vesicle antibody has high drug loading capacity and targeting effect. Biomimetic modification of red blood cells is a current hot spot. Many proteins on red blood cell membranes can inhibit the recognition of red blood cells by the immune system. Therefore, wrapping them on the surface of nanomaterials greatly reduces the immunogenicity of nanomedicine.
Cardiovascular diseases have become a major public health problem due to their high morbidity and mortality. Reducing the mortality of cardiovascular diseases is a major national demand. The preferred strategy for the treatment of these diseases is to replace damaged blood vessels, including natural blood vessels and artificial blood vessels. The patency rate of autologous blood vessels is high, but the source of donors is limited. For artificial blood vessels with a diameter less than 6 mm, the incidence of restenosis is high, and there is still no product for clinical use.
The research team of Professor Zhao Qiang of Nankai University uses two types of active substances that can induce tissue regeneration and regulate vascular function. Through the technical means of engineering materials science and chemical biology, respectively, the bionic construction of active biomaterials is used to create artificial blood vessels that can deliver active substances. And controllable release of nitric oxide hydrogel materials.
In addition to synthetic nanomaterials, people have also turned their vision to viruses. The virus itself is a natural nanostructure. When it is combined with fluorescent nanotechnology, it can provide the possibility to observe the virus infection process in real time.
Cui Zongqiang, a researcher at the Wuhan Institute of Virology, Chinese Academy of Sciences, has established a new single-virus, single-molecule, and ultra-high resolution imaging technology to dynamically analyze key molecular events such as virus invasion, uncoating, integration, latency-activation, and host interaction in real time. And mechanism. At the same time, a variety of functional nanodevices have been created to realize single-molecule event detection, highly sensitive multi-mode biosensing, efficient drug delivery, and integration of diagnosis and treatment, which is of great significance to the biomedical application of viral nanomaterials.
Another cutting-edge research direction of the combination of autologous and artificial is brain-computer interface research. The intersection of biomedicine and automation/data science, brain-computer interface research may bring about the next industrial revolution, which is of epoch-making significance. However, the current experimental raw materials such as high-density electrodes are still monopolized by foreign countries, and it is necessary to find a breakthrough in the combination of nano-materials.

Improve the efficiency of nano-drug delivery

In the drug delivery research of brain diseases and tumors, drug delivery still has obstacles. Although nanomedicine has developed rapidly in the past 20 years, nanomedicine generally has the problem of focusing on design and neglecting efficacy. This is an urgent need for breakthroughs and reforms. This view has become the consensus of nanomedicine research scientists.
Tumor tissues have more vigorous physiological activities, and weak acidity is a completely different microenvironment from normal tissues. When nanomedicine is delivered, the processes of circulation in the body, enrichment in the tumor area, cell uptake, deep penetration of the tumor, and release from the lesion site are very complicated. Aiming at the problem that it is difficult to take nanomedicine in the deep area of the tumor, the research team of South China University of Technology researcher Du Jinzhi used the tumor’s acidic environment to design a nanomedicine with variable size. Taking pancreatic cancer as an example, under normal blood pH environment, large size Nanoparticles are enriched on the surface of the tumor, and after reaching the tumor site, they release small-sized drugs to osmotically kill through redox reactions.
Tumor-associated macrophages are a key node of the tumor microenvironmental regulatory network. By reprogramming macrophages, the tumor microenvironment can be reshaped and drug resistance can be overcome. Therefore, drug-resistant tumors need a comprehensive treatment strategy, which must be used in combination with tumor cells and microenvironment. Huang Yongzhuo, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and his research team focused on the drug resistance of the three main tumor therapies (chemotherapy, molecular targeted therapy, tumor immunotherapy), and developed co-delivery technology to regulate tumor-associated macrophages To overcome resistance. For example, they designed a tumor microenvironment-responsive drug delivery system to modify a tumor enzyme-sensitive penetrating peptide on liposomes to achieve targeted co-delivery of simvastatin and the chemotherapy drug paclitaxel. This treatment strategy has a significant therapeutic effect on drug-resistant lung cancer.
In normal cell activities, autophagy controls many important functions. Regarding the question of whether tumor cells can be activated based on this characteristic, the traditional view is that autophagy induced by nanomaterials is unsafe. However, It is now gradually being used to kill tumor cells. Zhang Yunjiao, associate professor of South China University of Technology, regulates the properties of nanoparticles by modifying the surface of materials, controlling the size and morphology, and adopting the method of "promoting death and autophagy" on tumor cells, and "promoting survival and autophagy and suppressing death on normal cells. Autophagy” strategy. Modification of functional short peptides on rare earth up-conversion luminescent nanomaterials, or adjustment of nano-size screens, realizes the artificial adjustment of the above strategies.
In the process of drug delivery, it is not only necessary to consider biocompatibility and release efficiency, but also how to improve the accumulation of drugs at the lesion site to accurately target the tumor area. Yan Xiyun‘s team used ferritin detection as a new generation of immunohistochemical detection method and applied it to the treatment of malignant brain abuse. Ferritin itself is easy to modify and transform, and can cross the blood-brain barrier. Brain tumors consume a large amount of it. Loading drugs on ferritin breaks the barrier of artemisinin insensitivity to cerebral malaria. It is in the development of malaria treatment. Take a new step.
Humans have group attributes, and tumor cells are not alone. In the process of cancer treatment, tumor cells will have stress escape behaviors. They are not sensitive to traditional treatment. In the face of this situation, "encircling, chasing and intercepting" will not work. Or "blocking" triggers new thinking. Associate Professor Liu Dandan of Hebei University and his team established a tumor stem cell model and constructed a targeted nano drug delivery system to overcome treatment tolerance. They used exocrine HSP90 and nanocells to co-localize to inhibit the initiation of the therapeutic protection mechanism. At the same time, the tumor stem cell nuclear targeting nanosystem inhibited DNA damage repair, and finally increased the sensitivity of its drugs and traditional treatments through homologous targeting and "unblocking induction". Under the above-mentioned joint action, the goal of overcoming treatment tolerance and improving treatment efficiency is achieved.

One stone, two birds, one treatment

The ultrasound contrast agent developed by Dr. Liang Xiaolong of Peking University Third Hospital has increased the drug loading of the drug-carrying contrast agent and reduced toxic and side effects.
In the process of fighting against tumors, scientists found that even if the treatment effect of the originally effective drugs began to decrease when they were used later, this may be caused by the tumor‘s drug resistance mechanism, which is complicated by the tumor itself.
In order to achieve better therapeutic effects, people usually use combination drugs for synergistic effects. Ultrasound is widely used in cancer diagnosis and treatment because of its real-time and strong penetrability. Dr. Liang Xiaolong designed an amphiphilic camptothecin-fluorouridine drug conjugate, which was self-assembled and loaded into a nanometer compound liposome nanomedicine. In tumor cells, the sonoporation effect can cause materials to accumulate in the tumor cells. Ultrasound can target the microbubble structure and transform into nanoparticles, and then interact with esterase and acid to break the ester bond and release the drug, which is significant under the combined action Improve efficacy.
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