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New methods for treating cancer through photothermal agents molecules developed

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/

2020 BME International Graduate Admission

I. About the Programs  

There are two types of full-time graduate programs offered in our department: PhD Program and Integrated Master-PhD Program. All programs are taught in English.  

The PhD Program is for four years. The Integrated Master-PhD Program is for five years (two years for Master and the other three years for PhD).

 

II. Major Research Areas

1. Mechanomedicine

This direction is devoted to i）the study of tissue and cell mechanical properties in various diseases from the picometer scale to the macro scale and ii) the mechanism studies of how various mechanical signals regulate the specific tissues and organs and iii) the translation and application of basic research findings in the field i) and ii) to clinical practice and lead to the development of new diagnosis and therapy techniques.

Faculty:

Xingyu Jiang: research interests include microfluidic chips and nanobiomedicine.

Bin Tang: research interests include biomechanics, biological materials, nanometer materials, Micro nano biomaterials.

Chao Liu: research interests include the mechanobiology of bone cells and stem cells, tissue engineering of bone tissue for regenerative medicine applications, and bone-interfacing implants.

 

2. Multiscale/multimodal biomedical imaging

This direction is the cumulation of various interdisciplinary research that include optical, acoustic, electrical, magnetic resonance, nuclear and electronic imaging. The importance of this field is in its ability to decipher and solve critical issues in life sciences, covering a broad spatial and temporal range from micro-level to macro-level. It further provides the tools needed to understand the basic principles of life science. In particular, biological process and disease pathogenesis can be precisely and comprehensively investigated.

Faculty:

Dayong Jin: research interests include physical, engineering and interdisciplinary sciences, with expertise covering biomedical optics, nanotechnology, microscopy, diagnostics and automation devices.

Changfeng Wu: research interests include the development of fluorescent probes, biosensors, spectroscopic and imaging techniques for biomedical applications.

Lei Xi: research interests include development of novel optical imaging techniques for fundamental and clinical applications including photoacoustic microscopy, photoacoustic microscopy, optical coherence tomography, diffuse optical tomography and fluorescence molecular tomography.

Fangyi Chen: research interests include the development of the instruments in otolaryngology, in vivo study of the cochlear mechanics and functional assessment of the hearing and vestibular systems in animal models.

Kai Li: research interests include nanomedicine, molecular imaging and molecular probes.

Chao Liu: research interests include the mechanobiology of bone cells and stem cells, tissue engineering of bone tissue for regenerative medicine applications, and bone-interfacing implants.

Quanying Liu: research interests include methodological developments of EEG source-level analysis and EEG-fMRI network analysis; Modelling autonomous vehicles (AV) – human interactions; Computational models of human decision making and the neural representation; Non-invasive brain stimulation to modulate human behavior and cognition.

Yiming Li: research interests include super-resolution Imaging; Adaptive optics; Biomedical image processing; Correlative light and electron microscopy.

 

3. Wearable devices and wireless health monitoring

This direction is dedicated to developing new wearable devices with application in biomedical engineering, covering all scales, from sensor/circuit level to systems and applications.

Faculty:

Xingyu Jiang: research interests include microfluidic chips and nanobiomedicine.

Changfeng Wu: research interests include the development of fluorescent probes, biosensors, spectroscopic and imaging techniques for biomedical applications.

Mingming Zhang: research interests include flexible drive technology, intelligent control and human-computer interaction, wearable exoskeleton rehabilitation robots, and EMG/EEG based pattern recognition algorithms.

 

4. Biomedical MEMS

This direction is a research field which integrates mechanical elements, sensors, actuators and electronics on a single chip through microfabrication technology. By combining multiple traditional chemical/biological analysis functions into one chip, Bio-MEMS has been widely used in genomics, proteomics, minimally invasive surgeries, single cell analysis and implantable microdevices.

Faculty:

Xingyu Jiang: research interests include microfluidic chips and nanobiomedicine.

Lei Xi: research interests include development of novel optical imaging techniques for fundamental and clinical applications including photoacoustic microscopy, photoacoustic microscopy, optical coherence tomography, diffuse optical tomography and fluorescence molecular tomography.

Bin Tang: research interests include biomechanics, biological materials, nanometer materials, Micro nano biomaterials.

Mingming Zhang: research interests include flexible drive technology, intelligent control and human-computer interaction, wearable exoskeleton rehabilitation robots, and EMG/EEG based pattern recognition algorithms.

 

5. De novo regenerative engineering

The main focus of this direction is to stimulate de novo tissue regeneration inside patients’ body using various strategies, including applying physical and/or chemical stimuli, biomaterials, as well as stem cells.

Faculty:

Decheng Wu: research interests include biomedical polymers and hydrogels, medical dressings and devices, bioimaging, drug delivery, tissue engineering

Bin Tang: research interests include biomechanics, biological materials, nanometer materials, Micro nano biomaterials.

Kai Li: research interests include nanomedicine, molecular imaging and molecular probes.

Qiongyu Guo: research interests include temperature-sensitive shape memory materials, transcatheter arterial chemoembolization, cellular liver model for TACE and artificial cornea construction

 Ho Chun Loong: research interests include synthetic biology and protein engineering

 Chao Liu: research interests include the mechanobiology of bone cells and stem cells, tissue engineering of bone tissue for regenerative medicine applications, and bone-interfacing implants.

 

6. Computational medicine for big data and health informatics

Research in this direction focuses on utilizing ever-increasing volume of medical and health data to provide evidence and guidance for disease diagnosis, personalized treatment, risk analysis and prediction, and lifestyle intervention.

Faculty:

Dayong Jin: research interests include physical, engineering and interdisciplinary sciences, with expertise covering biomedical optics, nanotechnology, microscopy, diagnostics and automation devices.

Fangyi Chen: research interests include the development of the instruments in otolaryngology, in vivo study of the cochlear mechanics and functional assessment of the hearing and vestibular systems in animal models.

 Ho Chun Loong: research interests include synthetic biology and protein engineering

Quanying Liu: research interests include methodological developments of EEG source-level analysis and EEG-fMRI network analysis; Modelling autonomous vehicles (AV) – human interactions; Computational models of human decision making and the neural representation; Non-invasive brain stimulation to modulate human behavior and cognition.

Yiming Li: research interests include super-resolution Imaging; Adaptive optics; Biomedical image processing; Correlative light and electron microscopy.

 

III. SUSTech Graduate Scholarships  

SUSTech welcomes applications from students all over the world. All international graduate students admitted by SUSTech will be awarded the scholarship.  

PhD Program: The PhD scholarship is RMB126,700 (Approx. USD18,098)/year, plus a possible performance-based award of RMB20,000 (Approx. USD2,857)/year. The performance-based award will be evaluated by the SUSTech academic departments and approved by the Graduate School.  

Integrated Master-PhD Program: During the Master study period, the Integrated Master-PhD scholarship is RMB83,700 (Approx. USD11,955)/year, plus a possible performance-based award of RMB10,000 (Approx. USD1,428)/year. Student who completes the Master study successfully and becomes a PhD candidate will receive the PhD scholarship.

 

IV. Cost for Reference  

Tuition fee: RMB35,000/year (Approx. USD5,000) during the Master study period, and RMB40,000/year (Approx. USD5,715) during the PhD study period. Registration fee: RMB500 (Approx. USD71).  

Accommodation fee: RMB 18,000/year (Approx. USD2,570) for a single room in the graduate student dormitories on campus.

 

V. How to Apply  

1. Eligibility of International Applicants

Bachelor’s degree holder for Integrated Master-PhD Program applicants. Master’s degree holder for PhD Program applicants. Language competence: TOEFL 85 or above; or IELTS 6.5 overall or above, with no sub-scores lower than 6.0.  

2. Application Deadline:

Please email the required documents (in PDF format) to the contact listed below before June 15, 2020. The subject of email should be: Application for SUSTech PhD/Integrated Master-PhD Program Admission 2020-International Student-Name.

3. Required Documents:

(1) Application Form (Please click here to download the “Application form”)

(2) Personal statement, which should include study and work experience, reasons for application and study proposal.

(3) Degree certificates and academic transcripts, which must be original documents or notarized copies. If applicants are university students, they shall also provide an official pre-graduation certificate/letter showing their student status and stating the expected graduation date. For all documents in languages other than Chinese or English, notarized copies of translations in Chinese or English need to be provided.

(4) Photocopies of language proficiency certificates.

(5) Two letters of recommendation with appropriate contact details.

(6) A photocopy of passport or other government issued ID.

(7) Other documents that prove academic abilities.  

Hard copies of the above documents are required. Application materials will NOT be returned regardless of the result of application.

 

VI. Evaluation and Admission  

Applications will be considered on the basis of the documents provided by the applicants. An interview and/or additional tests may be needed.  

Offer letters will be issued to successful applicants by the SUSTech Graduate School Admissions Office following the release of the application review results around June 2020.

 

VII. Visa Application and Registration

Admitted students should bring their passport, Letter of Admission, Visa Application Form (JW202/JW201), as well as other required documents to the Embassy or Consulate of the People’s Republic of China for a student visa (X1 visa). Students shall come to SUSTech for registration during the dates indicated by the admission package with the required documents. Normally, the registration period is in late August. Students must enter China with an ordinary passport and an X1 visa, and must apply for a Residence Permit within 30 days of arrival in China.  

All students should present the passport and other necessary original or notarial degree certificates upon registration at SUSTech for enrollment qualification review. Students who fail the enrollment qualification review will be disqualified from enrollment.

 

VIII. Enquiries

Xiaowen Lin (Miss)

Department of Biomedical Engineering, SUSTech

Tel: 0755-88015151

Email: bmezb@sustech.edu.cn;

SUSTech BME official website: http://bme.sustech.edu.cn/en/

Transparent models of organs to deliver better health care

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