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State of the Art in Nanomedicine

Yujun Song1,2,3 and Wei Hou1

1University of Science and Technology Beijing, Center for Modern Physics Technology, School of Mathematics and Physics, 30 Xueyuan Road, Haidian District, Beijing 100083, China

2Zhengzhou Tianzhao Biomedical Technology Company Ltd., Zhengzhou New Technology Industrial Development Zone, 7B-1209 Dongqing Street, Zhengzhou 451450, China

3Key Laboratory of Pulsed Power Translational Medicine of Zhejiang Province, Hangzhou Ruidi Biotechnology Company Ltd., Room 803, Bldg. 4, 4959 Yuhangtang Road, Cangqian Street, Hangzhou 310023, China

1.1 Intractable Diseases and Development of the Related Novel Therapy and Medicines

Lots of people get sick now and then in their lives, reducing their quality of life and even threatening their lives. Many diseases not only cause great suffering for people themselves but also for their families and then of the whole society, particularly for those intractable diseases, such as tumors or cancers, rheumatoid arthritis, cerebrovascular diseases (e.g. stroke, cerebral thrombosis, myocardial infarction), neural diseases (e.g. Parkinson's, Alzheimer's, depression), recurrent and infectious skin diseases (particularly relating to blood, endocrine, and immunity), and highly contagious and lethal infectious diseases (e.g. HIV, COVID-19), and so on. Among them, cerebrovascular diseases are the first killers of people, particularly for those more than 50 years old. There were about 1.79 million people in 2016 who died of these kinds of diseases all over the world, about 31% of global causes of death, according to the statistics of the World Health Organization (WHO). Cardiovascular outpatients in China are already more than 0.29 billion (B). Nearly three million people die from cardiovascular and cerebrovascular diseases in China every year, about 51% of the whole causes of death. Cerebrovascular diseases are the fifth cause of death in 2016, with about 373 deaths per 1 M people. In addition, these kinds of diseases preserve features of high suddenness, high disability rate (about 75% of the surviving patients have varying degrees of loss of labor ability and 40% are severely disabled), high recurrence rate, and more multiple complications (e.g. coronary heart disease, myocardial infarct, vascular dementia, subarachnoid hemorrhage, respiratory tract infection, and sudden deafness). China has entered an aging society like other developed countries (e.g. Japan) even though China is still a developing country. The population of coronary artery disease (CAD) in China has increased from 2.27 M in 2016 to 2.53 M in 2020, with a compound annual growth rate of 2.7%. It was said that China's precision percutaneous coronary artery therapy (PCI) market has increased from ~$25.7 M in 2016 to ~101.4 M in 2020, with a compound annual growth rate of ~ 40.8%. The global market scale of PCI also shows a growth trend, which was $9.49 B in 2019 and was expected about $13.26 B in 2025 with a compound annual growth rate of ~ 5.4% (https://www.163.com/dy/article/HPGQBS2R051481OF.html; https://wenku.baidu.com/view/933bb2d7f624ccbff121dd36a32d7375a417c6c4.html?_wkts_=1711608332102&bdQuery=2023%E7%BB%8F%E7%9A%AE%E5%86%A0%E7%8A%B6%E5%8A%A8%E8%84%89%E6%B2%BB%E7%96%97%E5%85%A8%E7%90%83%E5%B8%82%E5%9C%BA%E8%A7%84%E6%A8%A1).

Although cancers are the second killers of people, next to cerebrovascular diseases, the pain and burden of patients caused by cancers far outweigh the former due to their characteristics of chronic redundant diseases. It is said that there were about 19.29 M new cases of cancers, among which there were 10.06 M male cases and 9.23 M female cases according to the statistics in 2020. There were about 9.96 M death cases, including 5.53 M male cases and 4.43 M female cases. It is expected that there will be more than 21 M new cases in 2030 [1-3]. There are about 4.82 M and 2.37 M new cases of cancers, and about 3.21 M and 0.64 death cases of cancers, in China and the United States, respectively [1]. Partially thanks to innovative drugs and therapies promoted by medical technology, the overall trend of death cases of cancers in the United States is accelerated down since 1991 [1]. It is predicted that the new cases and death cases in 2023 will be continuously reduced by 410 K and 30 K compared with those in 2022. However, in China, the new cases and death cases of cancers in 2022 increased by 250 K and 210 K compared with those two years earlier (2020), and the 2022 death/new incidence rate in China is far more than that in United States (67% versus 27%) [1]. The death cases of lung cancers is the first among all death cases in China, and then the summed death cases of liver and pancreatic cancers. Particularly, the cases of liver cancers in China are almost half of the cases in the world. For many cases, cancers were found to be mostly the terminal stage [4-6]. While, thanks to vigorous anti-smoking measures in the United States, the first death case is breast cancer, not lung cancer, in the United States. The survival rates for some special cancers in China are lower than those in the United States, particularly for breast cancers and colorectal cancers. It is also said that cancer prognosis in China is much worse than that in the United States. China needs to make more efforts to provide effective cancer treatment and improve universal health coverage. New medicine and therapy of high anti-cancer efficiency are extremely urgent currently, especially for China. At the same time, the global market of anti-tumor medicine has increased to $192.2 B in 2022 with a compound annual growth rate of ~12.7% while in China, the sales of anti-tumor drugs have been showing a steady growth trend in recent years. The market size of anti-tumor drugs reached $28.2 B in 2020 and will have an estimated compound annual growth rate of ~16.1% from 2020 to 2025.

As for hyperuricemia and gout, there were about 1.03 billion (B) outpatients all over the world and about 0.18 B in China in 2022. The global market for gout medicine was about $3.0 B. The gout medicine market in China will grow rapidly in the future, which is expected to be about $1.54 B in 2030. China has been known as the country with the largest population of diabetes in the world. The total number of people related to diabetes exceeded 260 million in 2018, including 114.39 M diabetes outpatients and 148.70 M pre-diabetes population. It is forecasted that the number of diabetes people will reach 320 M, which will create a huge market for diabetes medicine, with a potential scale expected to reach $19.3 B.

There are four types of neural diseases: absence of symptoms, release of symptoms, irritation and shock, such as Parkinson's, Alzheimer's, Depression, and Huntington's diseases. There are more than 0.1 B people more than 15 years old with various mental disorders in China, among which there are about 16 M patients with severe mental disorders and most of the rest are people with mental or behavioral disorders such as depression or autism. These kinds of illnesses not only torture patients but also haunt their families for a long time. Particularly, they preserve some certain psychological infectivity (e.g. resulting in mass suicide groups), leading to great social harm. Developing these kinds of drugs for anti-mental disorders has to overcome the obstacle of passing the blood-brain barrier (BBB). It is more difficult for these drugs into nerve cells to break through the protective membranes of dendrites, myelin sheaths, axons, terminals, etc.

Clearly, fighting these intractable diseases is a long and arduous task for human beings, whose key is to develop diagnosis methods for early disease identification, innovative drugs, and subversive therapies. Starting from this century, medicine and health care entered into a rapid transformation period promoted by the interdisciplinary crossover of life science, biology, biophysics, biochemistry, nanotechnology, and information technology [7, 8]. As a result, many creative medicine or medical technologies sprout recently, such as personalized medicine, precise medicine, nanomedicine, and lots of innovative therapies, such as gene therapy (e.g. mRNA, DNA), targeting therapy (e.g. cell targeting, tumor microenvironment targeting), immunotherapy (e.g. PD1, PD-L1, vaccine, CAR-T,), new physical field ablation therapy (e.g. nanosecond pulsed electrical field (nsPEF) ablation), new physicochemical therapy (e.g. ferroptosis, cuproptosis, photothermal therapy, photodynamic therapy, magnetothermal therapy, magnetodynamic therapy), and heavy particle radiation therapy (e.g. proton beam radiation, neutron scattering radiation, boron neutron capture therapy) [7-21].

Particularly, nanomedicines, which are translated from some functional nanomaterials, deal with nanoscale matters that can be used in biomedicine or biomedical engineering as bioprobes for the detection of biomolecule, organelle, cells or tissues, or as biosensors for the diseases or pathological metabolism diagnosis, or special drugs for some disease treatment or life function regulation. Based on nanodrugs and nanomedical engineering, lots of disruptive solutions have been advanced for the treatment of intractable diseases, such as anti-tumor nanomedicines [22], nanodrugs for rheumatoid arthritis [23], efficient nanodrugs for nerve or brain diseases by overcoming brain-blood barriers...