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The human body is like a sophisticated machine, with various organs working every day to maintain daily life activities. But sometimes, just like machine parts are damaged, organ damage also happens frequently. According to data released by the World Health Organization, the number of people who die directly or indirectly from organ damage each year exceeds more than 50% of the total number of deaths worldwide.

Organ damage is a common problem in all clinical departments. In the absence of effective methods/drugs for the clinical treatment of organ damage, "we would like to propose the use of nanotechnology to develop some new nanodrugs with unique functions to efficiently repair damaged organs." Professor Ni Dalong of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine told Shanghai Science and Technology.

"Last year, I was deeply honored to summarize my research results into the concept of 'Nano-Repair Medicine' for the first time, and was fortunate to be the only biomaterial researcher to win the award that year." Ni Dalong said that being selected for the 2023TR35 (Asia Pacific) is both an honor and a new starting point for his scientific research work. "I will continue to deepen the research and development of organ damage repair materials and innovative strategies. Taking this as an opportunity, I will refuse to win by doing nothing, continue to surpass myself, and turn the pressure brought by this honor into a driving force for progress."

01. Provided innovative strategies for repairing multiple organ damage for the first time

Organ damage, such as acute liver/kidney damage, bone and joint diseases, ischemic cardiovascular and cerebrovascular diseases, etc., usually greatly impairs the normal function of the body and even threatens life. Ni Dalong introduced that in clinical diagnosis and treatment, organ damage is usually diagnosed after symptoms appear. Once diagnosed, the current clinical treatment options are usually to remove the causative factors (such as organ damage caused by chemotherapy) and provide organ support treatment.

"If we can use nanoprobes/drugs with diagnostic functions to detect and actively intervene in damaged organs in the early stages of injury, it may be possible to reverse the damage and achieve complete repair of the organs."In the absence of effective methods/drugs for the clinical treatment of organ damage, Ni Dalong's research shows that nano-repair medicine can achieve specific repair of organ damage and has great potential in clinical practice.

Ni Dalong first proposed the concept of nano-repair medicine and provided a variety of innovative strategies for organ damage repair. "We want to actively intervene in the early stages of organ damage or prevent the further deterioration of mid- and late-stage organ damage. Given that many organs are regenerative, we consider using nano-drugs to regulate the physiological homeostatic microenvironment of organ damage, including physical and chemical homeostasis regulation, metabolic homeostasis regulation, and immune homeostasis regulation, in order to maximize the preservation of organ function or even reverse damage."

Innovation also brings challenges. How to balance the innovation and practicality of materials?

It is undoubtedly a challenge to develop innovative nanomedicines that can specifically repair organ damage and have never existed before. The synthesis and preparation of many reported nanomedicines are relatively complex, which limits their practicality and clinical translation potential."The biggest challenge in our research is to find nanomedicines that are easy to prepare, can be mass-produced, meet clinical needs, and are highly innovative."

"At present, our research may focus more on innovation, and we will innovate according to the actual needs of clinical organ damage." Ni Dalong is actively promoting clinical transformation with the clinical departments and pharmaceutical companies of Ruijin Hospital, hoping to achieve efficient repair of organ damage as soon as possible and benefit clinical patients.

02. “Using nanomedicine as a tool to answer clinical questions”

"We mainly communicate actively with doctors in various clinical departments, use nanomedicines to answer or solve clinical problems based on clinical difficulties and pain points."

Ni Dalong actively cooperates closely with clinicians to conduct research based on clinical needs, such as regulating organ physicochemical homeostasis (redox homeostasis, acid-base balance homeostasis) to repair acute liver/kidney/lung damage, regulating metabolic homeostasis to treat osteoarthritis, and regulating immune homeostasis to treat osteoporosis.

"An ideal nanomedicine should be universal."Ni Dalong hopes that the new nanomedicine developed by the team can repair the common pathological and physiological characteristics of organs such as the liver and kidneys, break the boundaries between clinical departments, and achieve universal repair effects. "At the same time, it can also provide 'tailor-made' diagnosis and treatment plans for patients with complex multi-organ injuries, achieve personalized repair, and meet the specific needs of patients."

The following is a dialogue between Shanghai Science and Technology and Ni Dalong:

@Shanghai Technology

What do you think are the potential or limitations of nanomedicine in repairing organ damage?

@Ni Dalong

One advantage of nanomedicine is that it can undergo specific functional modifications, including size and morphology regulation, surface modification, etc. Nanomedicine can be modified according to the repair needs of different organ damage.

For example, we can achieve organ-specific repair by regulating the size of nanoparticles. For example, nanoparticles with a size of about 10-100 nanometers will accumulate in the liver and can be used to specifically repair liver damage. When the size of nanoparticles is reduced to 1-2 nanometers, nanoparticles are metabolized by the kidneys and are more suitable for repairing acute kidney injury.

@Shanghai Technology

What stage of research are we in now?

@Ni Dalong

We have not yet reached the clinical application stage. We are now mainly synthesizing nanomedicines with special functions according to clinical needs, and verifying whether they have the expected repair effect in organ damage through relevant cell experiments and animal experiments. At the same time, we have also developed nanomedicines that are easy to synthesize and clinically transformed, which have shown excellent therapeutic effects in lung injury and inflammatory bowel disease. The nanomedicine is currently in the safety evaluation stage, and we look forward to conducting clinical trials as soon as possible.

@Shanghai Technology

Have you ever had the experience of asking questions during the scientific research process, and what did you gain from it?

@Ni Dalong

After returning to China, I conducted genetic screening with clinicians and found some genes that were specifically expressed in patients with osteoarthritis. I asked the clinicians whether the upregulation of these genes was beneficial or harmful.

Clinicians were also unsure, so we decided to study this using transgenic technology. We knocked out these genes and observed that the bones and joints of mice lacking these genes were more susceptible to disease and more severely damaged, indicating that the upregulation of these genes is to protect the bones and joints and prevent the disease from worsening.

After answering this question, we further thought that since the upregulated genes are beneficial, whether we can use nanomedicines with anti-inflammatory properties to carry these beneficial genes to achieve the joint regulation of physical and chemical homeostasis and metabolic homeostasis to repair osteoarthritis. After the relevant work was published, the editor-in-chief of the top journal in the field of bone and joint diseases made a special highlight comment (Nat. Rev. Rheumatol., 2023, 19,537-539), which affirmed our research work.

It was this question raised in the communication with clinicians that inspired us to base our research on clinical problems and be guided by clinical needs, and finally achieved a series of organ damage repairs, including repair of acute liver/kidney/lung damage (Adv. Mater. 2019/2022), inflammatory bowel disease (Sci. Adv. 2022), osteoporosis (J. Am. Chem. Soc. 2023), osteoarthritis (Sci. Adv. 2023), etc. Our cross-integration of medicine and engineering has not only answered clinical problems and solved clinical needs, but also made our contribution to the comprehensive promotion of the construction of a healthy China.

The views of companies and experts do not represent the official position

Author: Xu Zhi

Edited by: zy