Exclusive Interview with Professor Shi Xiangyang of Donghua University: My Years in the U.S. Taught Me That Doing Scientific Research Is Best Done Back Home

In 2008, a young man in his thirties stood at Pudong Airport, laden with numerous bags.

“I’m back, and this time I’m staying for good. Contributing to the nation’s medical cause is more rewarding than anything else,” he said.

He isProf. Xiangyang ShiAfter studying abroad for many years, he has finally returned to his homeland. During his time at the University of Michigan in the United States, he served as a Research Assistant Professor. Upon returning to China, he was invited to continue his affiliation and currently serves as a Visiting Research Fellow at the University of Michigan’s Institute for Nanotechnology in Medicine and Biological Sciences. He also concurrently holds the position of “Invited Director of Nanotechnology” at the University of Madeira in Portugal. His academic standing is considerable; he serves as Associate Editor-in-Chief for the China region of the Wiley journal *WIREs Nanomedicine and Nanobiotechnology*, on the editorial board of the American Chemical Society’s flagship journal *Bioconjugate Chemistry*, and is a Senior Member of the Chinese Chemical Society, Executive Director of the Beijing Society of Physiological Sciences, and Council Member of the Shanghai Society of Biophysics.

This time, driven by the aspiration to advance China’s biomedical nanotechnology, he returned to Donghua University, where he served as Professor, Doctoral Supervisor, and Deputy Dean of the College of Chemistry, Chemical Engineering and Biotechnology (now the College of Biological and Medical Engineering).

In a fast-paced metropolis like Shanghai, one must always stay a step ahead. Therefore, Professor Shi Xiangyang has led his team to continuously innovate in the field of nanotechnology-based tumor therapy, developing“Functional Nanogels Loaded with Copper Sulfide Nanoparticles for Photoacoustic Imaging-Guided Photothermal Therapy of Tumors”(hereinafter referred to as tumor photothermal therapy) and other emerging technologies, have been achieving “China Speed” on the global stage step by step.

Recently, he has once again brought forth his new project—“Construction of Organic/Inorganic Nanohybrid Platforms for Precision Tumor Imaging and Therapy(hereinafter referred to as the organic/inorganic nanohybrid platform) stands at a crossroads in the translation of scientific achievements into practical applications. How will Professor Shi Xiangyang make his choice this time? Why did he choose to return to China despite holding a certain academic stature overseas? As a “returnee” scholar, what unique insights has he gained on the path of translating research outcomes into real-world applications? To answer these questions, commissioned by2022 2nd High-Value Patent Project Selection in the Field of BiomedicineInvitation,VCBeat Conducts an Exclusive Interview with Professor Shi Xiangyang

“When I chose to return to China in 2008, no one understood my decision. But now, my former colleagues abroad all say I made the right choice!” Speaking about why he decided to return to China, Professor Shi Xiangyang’s eyes were filled with pride.

In recent years, the state’s emphasis on talent has attracted many overseas professionals to return to China for career development; Professor Shi Xiangyang is one of them.

Professor Shi Xiangyang said: ""During my years abroad, I keenly felt that insufficient attention was paid to the cultivation of young researchers overseas."“Although you can enter the laboratory with professors and have many opportunities to serve as assistants to prominent professors, the space for fully realizing your own ideas and the opportunities for personal growth are quite limited due to constraints in the education system and talent development mechanisms. In contrast, our country places great emphasis on cultivating young talents and encourages innovation. I was fortunate to ride this wave of favorable policies, which enabled me to achieve these R&D outcomes.”

Since 2008, China has established numerous talent programs primarily aimed at recruiting renowned scientists from top international institutions and early-career researchers, helping them establish their own laboratories and careers in China.

Although Professor Shi Xiangyang achieved certain accomplishments in the international academic community, during his research tenure at the University of Michigan in the United States, he observed the challenging employment situation faced by his Chinese colleagues in the U.S. job market, while also recognizing the opportunities available in China. Consequently, he made a resolute decision to return to China.

Indeed, this is the case. In addition to the lack of emphasis on training scientific researchers, certain overseas policies and research environments have led many Chinese scientists working abroad to consider returning to China.

Visa issues have also become a major obstacle for Chinese scientists seeking to remain in the United States. The increasingly restrictive U.S. policies on international students have extended their impact to scientists working in the country. It has become progressively more difficult for many Chinese scientists to obtain H-1B work visas and permanent residency, forcing them to leave the United States after graduation.

The United States is pushing Chinese scientists away, while we are leveraging this trend to attract them back.

In addition to the talent introduction programs we just mentioned, the rapid development of national scientific research capabilities has also become one of the reasons for researchers to consider returning to China.

According to data released by the National Bureau of Statistics in February 2022, China’s total expenditure on research and experimental development (R&D) reached RMB 2.7864 trillion in 2021, a year-on-year increase of 14.2%. In the Global Innovation Index 2021 published by the World Intellectual Property Organization, China’s scientific and technological innovation capability rose by two places from the previous year, firmly maintaining its leading position among upper-middle-income economies. These figures clearly demonstrate that China has significantly heightened its emphasis on and investment in scientific research in recent years.

China’s growing strength, reduced geographical distance from loved ones, the narrowing gap in scientific capabilities between the two countries, and career bottlenecks encountered in the United States are all prompting an increasing number of overseas Chinese scientists, such as Professor Shi Xiangyang, to begin reflecting:“It seems more suitable to return to China for scientific research.”

After Professor Shi Xiangyang returned to China, the state, the government, and Donghua University provided him with well-equipped laboratories, ample research funding, and an outstanding team. Free from concerns, Professor Shi has been “accelerating” on his scientific research journey, achieving numerous remarkable results, among which is the recent “organic/inorganic nanohybrid platform.”

“In 2019, our photothermal therapy project for cancer attracted widespread international attention and also received”Sino-German Center for Research Promotion, National Natural Science Foundation of Chinasupport. However, at present, photothermal therapy still faces certain bottlenecks. This time, I aim to go further and push nanotechnology to its limits in both imaging and therapy.” When discussing the rationale behind researching “organic/inorganic nano-hybrid platforms,” Professor Shi Xiangyang frankly stated that it was driven by the pursuit of progress.

In simple terms, Professor Shi Xiangyang’s development of the “organic/inorganic nanohybrid platform” represents a comprehensive upgrade to “photothermal therapy.”

Because “photothermal therapy” is confined to a therapeutic modality with a relatively limited scope, it has minimal efficacy against deep-seated tumors, leaving considerable room for improvement in achieving comprehensive treatment. Although many researchers are currently exploring the combination of photothermal therapy with chemotherapy and immunotherapy to achieve systemic treatment, Professor Shi Xiangyang has decided to address the issue at its root by focusing directly on material engineering.

“We were initially focused on studying only one type of material, but I believe this approach is limited. For instance, inorganic molecules are particularly excellent materials for contrast imaging research, while organic molecules have unique therapeutic effects. I think that if we could integrate both into a hybrid material, wouldn’t that allow us to leverage the strengths of each and achieve1+1>2effects?” Guided by this idea, Professor Shi Xiangyang began to focus on developing an “organic/inorganic nanohybrid platform.”

Currently, "organic/inorganic nanohybrid platforms" have achieved dual functionalities for therapy and imaging.

In terms of imaging,This technology addresses the issue of insufficient diagnostic accuracy inherent in single-modality imaging. During tumor treatment, different imaging modalities offer distinct benefits and have their own advantages and limitations; relying solely on a single modality may fail to fully and accurately delineate the tumor and its boundaries.

By developing and constructing novel organic-inorganic hybrid nanoplatforms, structural imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) can be integrated with functional imaging techniques like fluorescence imaging or nuclear medicine imaging (e.g., single-photon emission computed tomography [SPECT] and positron emission tomography [PET]), thereby enabling more precise bimodal or multimodal imaging.

Therefore, to more accurately visualize tumors and their boundaries, improve the precision of subsequent treatments, and minimize unnecessary harm to patients caused by repeated imaging, Professor Shi Xiangyang leveraged an “organic/inorganic nanohybrid platform” to achieve the integration of various imaging technologies.

In terms of treatment,Professor Shi Xiangyang’s “organic/inorganic nanohybrid platform” can integrate drugs onto the surface or within the interior of nanoparticles, enabling passive targeting to tumor sites via the enhanced permeability and retention (EPR) effect. Furthermore, given that specific receptors are expressed on the surface of each type of tumor cell, active targeting and precise delivery of nanomedicines can be achieved by modifying the nanoparticle surface with specific ligand molecules.

In addition, Professor Shi Xiangyang’s research group has pioneered the intracellular loading of nanomedicines into macrophages or stem cells, leveraging their tumor-homing capabilities to achieve enhanced tumor diagnosis, therapy, or integrated theranostics. In recent studies, the group has also employed tumor-biomimetic targeting strategies using cancer cell membranes or macrophage membranes to coat nanomedicines, thereby enabling targeted theranostics in orthotopic tumor models.

Drawing on his extensive overseas experience, Professor Shi Xiangyang keenly recognized that this project would undoubtedly exert significant international influence. Consequently, he successfully secured funding from the National Natural Science Foundation of China’s International (Regional) Cooperation and Exchange Program.“A3 Forward-Looking Program Project”With the funding, international exchanges and collaborations were carried out with Osaka University in Japan and Ewha Womans University in South Korea.The “Organic/Inorganic Nano-Hybrid Platform” project has currently entered the laboratory phase, and we are seeking further collaborations to translate the project outcomes into clinical applications.

To this day, Professor Shi Xiangyang still regards the advancement of nanotechnology as his mission: “I entered the field of dendrimer research in 2002, and it has been 20 years as of this year. Currently, a keyword search for ‘dendrimers’ on Web of Science shows that both the total number of papers published and the total citation count by my research group over the past five years rank first.”Precisely because my team and I have been at the forefront of this field, we are better equipped and bear a greater responsibility to excel in this endeavor.”

Perhaps it is the sense of responsibility as an industry leader and the mission to promote medical development that keep Professor Shi Xiangyang from relaxing his efforts, continuously advancing the application of nanotechnology in medicine in China forward and upward.

Professor Shi Xiangyang’s “Organic/Inorganic Nanohybrid Platform” is now at a critical juncture for translation and implementation, yet he is struggling to find a corporate partner:“Our market still lacks companies with courage.”

Professor Shi Xiangyang believes that a scientific achievement capable of being translated into practical applications must meet three criteria: addressing clinical pain points, enabling mass production, and allowing for quality control. His “organic/inorganic nanohybrid platform” meets all three requirements, but it is currently stalled at the stage of finding a corporate partner.

Of course, it is not that no companies have contacted Professor Shi Xiangyang. Some pharmaceutical companies have also communicated with and consulted Professor Shi Xiangyang, but there is still a lack of follow-up and implementation at present.

“Many companies are currently approaching me to discuss collaborations, primarily seeking my technical consultancy. However, when it comes to further translation and implementation, they hesitate due to various reasons, fearing risks and lacking the courage to take the final step.” The dilemma currently faced by Professor Shi Xiangyang may well be a common challenge encountered by many researchers during the process of translating their scientific achievements into practical applications.

Indeed, from a business perspective, companies naturally need to assess risks and minimize potential losses. However, researchers also urgently require stable and capable capital support during the translation process. Although research institutions such as universities and hospitals can provide platforms and funding for researchers, truly entering the market still relies on capital active in the market environment.

Professor Shi Xiangyang has also reflected on this situation, suggesting that it may be partly due to researchers’ insufficient promotion of their own projects, which has prevented capable and innovative companies from recognizing these projects and understanding their significance and development potential. However, the market indeed lacks companies with the courage to drive innovative projects toward implementation. After all, the translation of scientific and technological achievements is not a one-sided effort by researchers alone; market cooperation is equally crucial.

“In the future, we hope to see more companies with courage, perseverance, and a sense of responsibility join our market, facilitating the translation and implementation of more valuable outcomes.”This is Professor Shi Xiangyang’s vision for the future of his project, and also our vision for the future of the market for translating scientific research achievements into commercial applications.

With high hopes for the future, Professor Shi Xiangyang once again participated in the 2022 Second Biomedical High-Value Patent Project Selection, following last year’s inaugural event. He aims to leverage this platform to raise awareness among more enterprises about the advantages and significance of the “Nano-Hybrid Platform,” thereby accelerating the translation and implementation of this innovative technology.