New strategies have been developed at Southern University of Science and Technology (SUSTech) that could see cancer treated in a less invasive manner.

Photothermal therapy (PTT) using near-infrared (NIR) light-absorbing agents to generate heat for tumor ablation locally has received considerable interest in recent years. PTT has become an important research direction for cancer treatment. However, traditional PTT methods suffer from several limitations, including complex synthesis of inorganic/organic photothermal agents (PTA), using high laser power density, and tissue damage from the high-temperature PTT.

The latest progress in applying low-temperature photothermal therapy examined the synthesis of small molecule PTAs with high PTCE, as there is enormous potential for biomedical applications.

Associate Professor Kai Li (Biomedical Engineering) has led his research group to publish a ground-breaking paper in the high-impact academic journal, Angewandte Chemi International Edition (Angew Chem Int Ed) (IF = 12.257). The paper was titled, “Photoinduced Nonadiabatic Decay-guided Molecular Motor Triggers Effective Photothermal Conversion for Hyperthermia Cancer Therapy.”

Their paper has made significant progress in studying the synthetic method of small molecule photothermal agents, and their applications in low-temperature photothermal therapy (PTT). PTT is an important research direction for cancer treatment. However, there are several side-effects and problems with traditional PTT techniques. It means that there is a significant need to develop a new photothermal agent-mediated low-temperature PTT strategy.

Their paper designed a new type of organic small molecules that are based on light-induced, non-adiabatic decay (PIND) effect. The co-delivery of the photothermal molecule with a heat shock protein 70 (HSP70) inhibitor (Apo) leads to suppressed HSP70 expression and realize a high-efficiency PTT tumor treatment at 43°C.

Associate Professor Jen-Shyang Ni, a fellow researcher, explained that when this sort of imine-based molecular motor is irradiated by lasers to an excited state, it will be affected by the strong intramolecular twisted charge transfer effect (TICT). The TICT supports passing through the conical cross (CI) process, which releases energy back to the ground state. It can be considered as a photo-induced non-adiabatic decay (PIND) phenomenon, which has almost no fluorescence emission. They can better convert light to heat and exhibits up to 90% efficiency, compared to existing commercial products.

Figure 1. The photophysical properties and working principle of light-induced non-adiabatic decay (PIND) organic small molecules

In animal experiments, the researchers developed a delivery system for tumor cells that used the thermal response technique. Following further experimental processes, they showed that their technique had a significantly better treatment effect than the control group. It proved the effectiveness of a combined treatment strategy, showing an efficient and straightforward photothermal conversion molecular motor that negates the need for introducing long-branch organic alkyl chains or other bulky substituents. Effectively breaking through the traditional limitations has opened many doors for new ideas in the development of small molecule, high-efficiency, photothermal agents.

Figure 2. C6TI/Apo-Tat NPs-mediated hypothermic PTT tumor therapy. (a) Temperature curve of 808 nm laser (0.5 W cm^-2) irradiated mice tumor site with time; (b) Tumor growth curve of tumor size with the time of different treatment groups; (c) Day 14 of different treatment groups Dissected tumor photographs; (d) HSP70 immunofluorescence staining and TUNEL staining analysis of in situ tumor tissue sections, scale = 100 μm

SUSTech is the first communication unit of the thesis. Associate Professor Jen-Shyang Ni is a co-first author of the paper. Associate Professor Kai Li was the sole correspondent author of the paper. Other significant contributions came from the HKUST-Shenzhen Research Institute and the City University of Hong Kong Shenzhen Research Institute.

The authors received support from the National Natural Science Foundation of China, the Science and Technology Plan of Shenzhen, and the High-Level Special Funds of SUSTech. They also acknowledge the Center for Computational Science and Engineering at SUSTech for theoretical calculation support, and the SUSTech Core Research Facilities for technical support. All in vivo procedures were approved by the Animal Ethics Committee of the Laboratory Animal Research Center of SUSTech.

Paper link: https://www.onlinelibrary.wiley.com/doi/10.1002/anie.202002516

Group introduction

Associate Professor Kai Li: http://faculty.sustech.edu.cn/lik/

Research Associate Professor Jen-Shyang Ni: http://faculty.sustech.edu.cn/nizx/

Chris Edwards | 04/11/2020

The rapid development of biotechnology has seen the dramatic increase in applications for transparent models of organs for the observation and study of the delicate three-dimensional structure of organs and mechanisms of diseases. An international collaboration led by the Southern University of Science and Technology (SUSTech) has made significant progress in the construction of transparent liver organs modeling liver cancer interventional treatments, providing significant help to researchers, doctors, and patients.

Assistant Professor Qiongyu Guo of Biomedical Engineering at the SUSTech led her research team to work with the National University of Singapore and Henan University to publish a paper in the high-impact academic journal, Biomaterials (IF = 10.273). The article was titled “Decellularized liver as a translucent ex vivo model for vascular embolization evaluation.”

Approximately 850,000 new cases of liver cancer are reported worldwide annually. Liver cancer has placed a heavy burden on society in many countries and is currently the leading cause of death for men under 50 years of age. Hepatocellular carcinoma (HCC), which accounts for 85%–90% of primary liver cancers, is the predominant pathological type of malignant liver tumors.

Transcatheter arterial chemoembolization (TACE), which applies embolic agents to selectively occlude tumor-supplying hepatic arteries, is currently the mainstay treatment for patients who have lost the opportunity for resection surgery. However, there is not an adequate model to evaluate embolization performance for TACE treatment, which has affected the development of new embolotherapies.

In vitro models such as microfluidics have been used to evaluate the performance of these agents. However, the materials used in the models do not correctly replicate the mechanical properties of blood vessels. The model channels are often too simple to simulate the complexities of HCC. The limited spatial resolution of X-ray-based instruments available for TAE/TACE and the lack of imageability of most solid embolic agents themselves prevent the accurate study of the penetration depth and embolization endpoints in animal models. Thus, the development of a new TACE model system that accurately evaluates embolic agents is vital for this clinical field.

Figure 1. Quantitative analysis of the vascular systems of a translucent liver model

The research group has proposed a new strategy for assessing vascular embolization by using decellularized whole livers as a clearing in vitro model. In recent years, decellularization has been used primarily for regenerating organs. The team developed a transparent liver by applying a strictly controlled decellularization perfusion method. They completely removed the cells while maintaining the extracellular matrix and the vascular system within the liver. The model of the liver was translucent, allowing the vascular system to be viewed through a variety of imaging tools (Figure 1).

Figure 2. Evaluation of different embolic agents in a cleared, isolated liver model

The researchers successfully used the translucent model to evaluate different types of embolic agents (Figure 2). They observed that the embolization endpoint of a liquid embolic agent depends strongly on the injection pressure and the location of the injection. Solid embolic agents tend to have a reduced density near the end of an embolization site. These findings confirm that particle size and penetration depth are two key factors that determine embolic distribution.

Figure 3. Dynamic monitoring of embolization kinetics of liquid embolic agent iodized oil

The research team also examined the embolization kinetics of TACE treatment, and for the first time, evaluated the correlation between the embolization pressure and the penetration depth as well as the liver morphologies in the decellularized liver model (Figure 3). This model enables the monitoring of the spatiotemporal location of embolic agents. The finding is critical for real-time analyses of the effectiveness of embolization formulations for TACE treatment.

This research opens up new methods for developing transparent organ models for visualization research and evaluation of clinical treatment methods. It will provide more effective assessment strategies for the translational research of various biotechnologies and biomaterials.

SUSTech research assistant Yanan Gao is the first author of the paper with research assistant Zhihua Li has made vital contributions to the paper. Assistant Professor Qiongyu Guo is the corresponding author of the article, and SUSTech is the first communication unit. Additional contributions came from the National University of Singapore (Department of Biomedical Engineering, Yong Loo Lin School of Medicine, and Mechanobiology Institute), the First Affiliated Hospital of SUSTech (Shenzhen People’s Hospital), SUSTech (Materials Science and Engineering, Academy of Advanced Interdisciplinary Studies), Henan University (College of Medicine), A*STAR(Institute of Bioengineering and Nanotechnology), Singapore-MIT Alliance for Research and Technology (CAMP), and Southern Medical University (Gastroenterology Department).

This research received support from the Key-Area Research and Development Program of Guangdong Province, National Natural Science Foundation of China, the startup funding from SUSTech, and the SMART CAMP and Mechanobiology Institute of Singapore funding. 

Paper link: https://www.sciencedirect.com/science/article/pii/S0142961220301010

Chris Edwards | 03/30/2020

On March 24, Southern University of Science and Technology (SUSTech) Chair Professor of Biomedical Engineering Xingyu JIANG was elected to the College of Fellows of the American Institute for Medical and Biological Engineering (AIMBE).

Dr. Jiang was nominated, reviewed, and elected by peers and members of the College of Fellows for “outstanding contributions in using micro-/nano-materials for multiplexed assays that improves the quality of healthcare and efficiency of biomedical research.”

Under special procedures, Dr. Jiang was remotely inducted along with 156 colleagues who make up the AIMBE College of Fellows Class of 2020.

The American Institute for Medical and Biological Engineering (AIMBE) is a non-profit organization that represents the most accomplished individuals in the fields of medical and biological engineering. AIMBE’s mission is to provide leadership and advocacy in medical and biological engineering for the benefit of society. It is an organization of leaders in medical and biological engineering, consisting of academic, industrial, professional society councils and elected fellows. The College of Fellows is comprised of experts in areas such as clinical practice, industrial practice, and education. Potential Fellows go through a rigorous peer-review and selection process.

Chair Professor Xingyu JIANG’s research interests include microfluidic chips and nano-biomedicine. Dr. Xingyu JIANG received funding from the National Outstanding Youth Science Fund in 2010, the Top Youth in 2013, the Special Allowance of the State Council in 2014, the Innovative Talents Promotion Plan of the Ministry of Science and Technology, and the Chief Scientist in the Key Special Project of the National Key Research and Development Plan of the Ministry of Science and Technology in 2019. He was one of the inaugural winners of the Xplorer Prizes from the Tencent Foundation in 2019. He has published more than 300 papers, and his research directions include microfluidic chips and nano-biomedicine.

Chris Edwards | 03/09/2020

A new study by Southern University of Science and Technology (SUSTech) has found a new form of luminescent material ideal for bacterial treatments that had previously shown themselves to be resistant to a broad range of drugs.

Department of Biomedical Engineering Associate Professor Li Kai led the research published in the high-impact journal Angewandte Chemie International Edition (Angew Chem Int Ed). The paper was titled “Planar AIEgens with Enhanced Solid‐State Luminescence and ROS‐Generation for Multidrug‐Resistant Bacteria Treatment.”

Figure 1. The design strategy of fluorine replacing planar AIEgens

Fluorescent materials have shown great potential in optoelectronics and biomedical engineering. However, one of the major flaws behind traditional fluorophores is that they suffer from aggregation-caused quenching (ACQ), a situation where the collection of fluorophores reduces the intensity of luminescence. The discovery of various types of aggregation-induced luminescent agents (AIEgens) provides a promising solution to address this challenge. However, it is still vital to find a simple and effective method to enhance solid-state luminescence of planar AIEgens, which would find significant commercial applications.

Figure 2. UV-vis and fluorescence spectra of planar AIEgens (DMA-AB-F and F-AB-DMA).

The research team designed and synthesized three pairs of planar AIEgens and studied their photophysical properties, intending to apply molecular engineering techniques to restrict the movement of the AIEgens in their aggregated state. Their results showed that they were able to inhibit their molecular movement and their non-radiative transition through the introduction of fluorine atoms to the aromatic ring. They hypothesized that the planar AIEgens they had developed would improve AIE performance and effectively promote the generation of ROS.

Figure 3. Antibacterial effect in vitro.

The research team tested the new AIEgens as photosensitizers against multidrug-resistant bacteria under a mouse model. In vitro testing (testing outside the body of a living organism) showed that their AIEgens would effectively kill MDR E. Coli and MRSA. In the follow-up in vivo testing on mice, they were able to show that their AIEgens would kill significantly more bacteria following photodynamic therapy than the control group.

Figure 4. In vivo antibacterial effect.

The study has proved a new direction in the treatment of multi-drug resistant bacterial infections through the use of reactive oxygen species expressed through the use of planar AIEgens. This unique approach provides more opportunities for researchers to develop a broad range of AIE photosensitizers for use in the biomedical industry.

Research Associate Professor Ni Jen-Shyang and masters students Min Tianling were the co-first authors. Associate Professor Li Kai was the correspondent author. The contributing units were the Department of Biomedical Engineering at SUSTech, the HKUST-Shenzhen Research Institute (SRI), and the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences.

The authors are grateful to the National Natural Science Foundation of China, the Thousand Young Talents Program, and the Science and Technology Plan of Shenzhen for financial support. The authors also acknowledge the Center for Computational Science and Engineering at SUSTech for theoretical calculation support and SUSTech Core Research Facilities for technical support.

Paper link: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202001103

Nanoscale technology is supporting more high-tech devices used in modern society than currently appreciated. The development and manipulation of nanostructures have developed rapidly in recent years and allowed for advances such as imaging and sensing devices with touch screens and high-resolution light-emitting diode (LED) displays.

Department of Biomedical Engineering (BME) Chair Professor Dayong Jin was part of an international collaborative research team that was published on March 4 in the high-impact journal, Nature. Their review article was titled, “Single-particle spectroscopy for functional nanomaterials.”

The piece focuses on the luminescent nanoparticles central to many advances with the opportunities and challenges for these technologies to reach full potential. It sought to understand how single nanoparticles behave, so scientists can develop new tools that support a broad range of modern applications such as personalized medicine, cybersecurity, and quantum communication.

The development of single-molecule measurements and the rapid progress in optical microscopy have made it possible to observe the fluorescence of single photons. Advances in this field could lead researchers to discover the underlying photophysics from the nanoscale – with “plenty of room at the bottom.” The article found many promising material candidates for a wide range of commercial and industrial applications, from quantum dots to carbon dots, fluorescent nano-diamonds, and nanoparticles fabricated from obscure minerals such as perovskite.

There are increasing challenges as scientists step ever closer to optimal nanoparticle design, mainly as there is an increasing demand for smaller and more efficient nanoparticles with desirable characteristics.

The research team focused on the development of uniform nanoparticles that are just a few nanometers in size. It is a significant challenge, along with controlling their size and shape, as new knowledge is needed about nanoparticle surface chemistry to better understand these properties, as well as their optical properties.

In a dynamic field such as nanoparticles, there is seemingly no limit except the ability of science and engineering to integrate their knowledge and skill. The paper examines opportunities for continued fundamental research that pushes at the cutting-edge of nanoscale technologies.

Professor Dayong Jin believes that there will be a future where nanoparticles can be used to develop biomedical signatures that answer personalized drug therapy questions from a single drop of blood.

He highlighted the point that everyday technology such as smartphones and touch screens are now the result of decades of research by scientists and engineers trying to answer fundamental scientific questions.

Professor Dayong Jin joined SUSTech in January 2019 and quickly established a research team of more than 40 people. The laboratory has built inorganic rare earth luminescent materials, organic rare earth complexes, super-resolution imaging, and time-resolved imaging research platforms.

Dr. Jiajia Zhou from the Institute for Biomedical Materials and Devices (IBMD) at the University of Technology Sydney (UTS) was the first author of the paper. She worked with Dr. Alexey I. Chizik from the Third Institute of Physics at the Georg-August University of Göttingen, Prof. Steven Chu of the Department of Physics at Stanford University and SUSTech Chair Professor Dayong Jin from the Department of Biomedical Engineering. All four authors were correspondent authors. The scholars acknowledge support from the Australian Research Council (ARC), the Discovery Early Career Researcher Award Scheme, the Shenzhen Science and Technology Program, and the Australia China Science and Research Fund Joint Research Center for POCT.

Article link: https://www.nature.com/articles/s41586-020-2048-8