Recently, the Microfluidic-Biomaterials Lab at the Southern University of Science and Technology (SUSTech) received the Chinese Scientists with Cell Press Best Paper Award 2020. Their paper, entitled “Electronic Blood Vessel,” was published in Matter, a journal under the Cell Press publishing organization that covers the field of materials science. The team from SUSTech developed an electronic blood vessel by using poly(L-lactide-co-ε-caprolactone) (PLC) which encapsulates liquid metal to make a flexible and biodegradable circuit. The electronic blood vessels could integrate flexible electrons with three layers of blood vessel cells to imitate and surpass natural blood vessels. It can effectively promote cell proliferation and migration in the wound healing model through electrical stimulation. It can controllably deliver genes to specific parts of the blood vessel through electro-transfection. Through a 3-month in vivo study of the rabbit carotid artery replacement model, the authors evaluated the electronic blood vessel’s efficacy and biological safety in the vascular system. They confirmed its patency through ultrasound imaging and angiography. The research paves the way for the integration of flexible, degradable bioelectronics into the vascular system, which can be used as a platform for further treatments, such as gene therapy, electrical stimulation, and electronically controlled drug release. In the future, the electronic blood vessel can be integrated with other electronic components and devices to achieve diagnostic and therapeutic functions. This will enhance significantly personalized medical functions by establishing a direct connection in the blood vessel tissue-machine interface. Cell Press is an internationally renowned academic publishing organization. Since 2015, it has looked at Chinese papers published in its journals and promotes the scientific research achievements of Chinese scientists in life sciences, materials science, and interdisciplinary science. Paper link: https://www.sciencedirect.com/science/article/pii/S2590238520304938
Recently, a research team led by Professor Changfeng Wu from the Department of Biomedical Engineering at the Southern University of Science and Technology (SUSTech) developed a series of highly bright polymer dots probes. Through the functionalization of polymer dots probes and application in expansion microscopy, fine subcellular structures with a resolution of ≈ 30 nm can be resolved on a conventional fluorescent microscope. Their research, entitled “Expansion Microscopy with Multifunctional Polymer Dots,” was published in Advanced Materials, a top journal in the field of materials science. Super-resolution optical imaging won the 2014 Nobel Prize in Chemistry for its ability to provide resolution below the diffraction limit. The current super-resolution technology mainly contains two categories, one of which relies on patterned illumination modulation and the other one based on single-molecule positioning. Expansion microscopy uses a completely different strategy that physically enlarges the samples to allow clear distinction of adjacent molecules that are originally within the diffraction limit. This method does not rely on a complex imaging system, and nanoscale resolution can be achieved on a common confocal microscope. However, the fluorescence brightness attenuation caused by chemical quenching and density dilution during sample preparation has long been a challenge for further applications. Changfeng Wu’s research group developed multifunctional polymer dots for application in multicolor expansion microscopy to address this issue. The fluorescence intensity of Pdots in ExM was up to 6 times higher than those achieved using commercially available Alexa dyes. The impressive brightness of the Pdots facilitated multicolor ExM, thereby enabling a variety of subcellular structures, such as mitochondria, clathrin-coated pits, and neuron synapses to be visualized on traditional fluorescent microscopes (Figure 1a-c). Furthermore, the research group combined polymer dots probes, expansion microscopy, and super-resolution optical fluctuation microscopy to achieve ultrahigh-resolution imaging of subcellular structures on a conventional wide-field microscope. As a result, this reflected the actual size of microtubules and the hollow membrane structure of mitochondria (Figure 1d-j). These findings highlight the immense potential of highly bright polymer dots for biological imaging. Figure 1. Three-dimensional super-resolution expansion and optical fluctuation imaging of subcellular structures The immunofluorescence staining of samples is tedious and time-consuming. To improve the efficiency of the project, Zhihe Liu, a postdoctoral fellow in the research group, designed an automatic cell immunostaining system (Figure 2). As a result, this could replace manual work for immunofluorescence staining experiments. Figure 2. Automatic cell immunostaining system Jie Liu, a doctoral student supported by the joint Ph.D. program between SUSTech and the Hong Kong Baptist University (HKBU), is the first author of this paper. SUSTech is the correspondence unit of this paper. The above research has been supported by the National Natural Science Foundation of China (NSFC), the National Key R&D Program of China, and the Shenzhen Science and Technology Innovation Commission. Paper link: https://doi.org/10.1002/adma.202007854
On May 22, 2021, the Department of Biomedical Engineering (BME) at the Southern University of Science and Technology (SUSTech) celebrated its 5th anniversary by holding an Achievement Exhibition. The achievement exhibition was made accessible for both online and offline participation. Yusheng ZHAO, Acting Vice President of SUSTech and Dean of the SUSTech Academy for Advanced Interdisciplinary Studies, attended the event. Yusheng ZHAO said that BME has developed rapidly in the past five years and has achieved remarkable results. He hopes that the department will continue to strengthen and grow in the future while also promoting the cross-integration of disciplines and innovation of advanced technology. Xingyu JIANG, Head of BME, expressed his gratitude to everyone who has helped and supported the development of BME over the past few years. He added that its success wouldn’t have been possible without the support of the leadership team at SUSTech, faculty members, students, and other volunteers that have assisted the department since its formation. All 17 research groups of BME participated in the exhibition, attracting more than 100 experts, scholars, faculty members, and students within SUSTech to participate in the event.
Recently, Kai Li’s laboratory at the Department of Biomedical Engineering of the Southern University of Science and Technology (SUSTech) has made significant experimental progress in tumor photodynamic immunotherapy. The research paper, titled “Acceptor Engineering for Optimized ROS Generation Facilitates Reprogramming Macrophages to M1 Phenotype in Photodynamic Immunotherapy” was published by Angewandte Chemie International Edition. Reprogramming tumor‐associated macrophage cells by photodynamic therapy (PDT) is a promising approach to overcoming the suppression of tumor microenvironment for boosted immunotherapy. It remains unclear how the reactive oxygen species (ROS) generated from type I and II mechanisms relate to the macrophage polarization efficacy. Prof. Li’s team designed and synthesized three photosensitizers with varied ROS‐generating effectiveness. Surprisingly, they discovered that the extracellular ROS generated from type I mechanisms are mainly responsible for reprogramming the macrophages from a pro‐tumor type (M2) to an anti‐tumor state (M1). In vivo experiments prove that the photosensitizer can produce effective suppression of the tumor growth, while the therapeutic outcome is eliminated with depleted macrophages. Overall, their strategy highlights the design guideline of macrophage‐activated photosensitizers. Here were the key findings from their analysis: 1. Three donor-acceptor (D-A) structured AIEgen photosensitizers have been synthesized using the compound triphenylamine as the electron donor, and their ROS-generating efficiencies are adjusted by using acceptor units with varied electron deficiencies. 2. Using commercial photosensitizers, such as chlorin 6 (Ce6) and rose bengal (RB), they discover that the extracellular ROS generated from type I mechanism rather than type II mechanism plays a key role in reprogramming the macrophages to M1 phenotype. This is of high importance in in vivo anti-tumor applications, taking into account the lower oxygen dependence of type I PDT mechanism and the hypoxic tumor microenvironment. 3. In vivo results suggest that the tTDCR nanoparticles can lead to a complete removal of a tumor in mice without any relapse, upon a single PDT treatment in the absence of any immune checkpoint inhibitor or immunoadjuvant. This would appear to be attributed to its excellent performance in the activating macrophages. Dr. Guang Yang, a post-doctoral at SUSTech, is the first author of this paper. Prof. Kai Li, also of SUSTech, is the corresponding author. Jen-Shyang Ni, Yaxi Li, Menglei Zha, and Yao Tu are the co-authors of the paper. This research was financially supported by the National Natural Science Foundation of China (NSFC), Ministry of Science and Technology of China (MOST), Guangdong Science and Technology Department, and the Shenzhen Science and Technology Program. Paper Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202013228
Optical tweezers are widely used in materials assembly, characterization, biomechanical force sensing, and the in vivo manipulation of cells and organs. The trapping force has primarily been generated through the refractive index mismatch between a trapped object and its surrounding medium. This poses a fundamental challenge for the optical trapping of low-refractive-index nanoscale objects, including nanoparticles and intracellular organelles. Prof. Dayong Jin, Chair Professor at SUSTech Department of Biomedical Engineering (BME) and Distinguished Professor at the University of Technology Sydney (UTS), was part of an international collaborative research team that published an article on February 18, 2021, in Nature Nanotechnology, titled as “Optical tweezers beyond refractive index mismatch using highly doped upconversion nanoparticles.” The research focuses on a technology that employs a resonance effect to enhance the permittivity and polarizability of nanocrystals, leading to enhanced optical trapping forces by orders of magnitude. This effectively bypasses the requirement of refractive index mismatch at the nanoscale. Figure 1. Comparison between optical trapping of low refractive index nanoparticles with or without doping by lanthanide ions The study shows that under resonance conditions, highly doping lanthanide ions in NaYF4 nanocrystals makes the real part of the Clausius–Mossotti factor approach its asymptotic limit, thereby achieving a maximum optical trap stiffness of 0.086 pN μm–1 mW–1 for 23.3-nm-radius low-refractive-index (1.46) nanoparticles, that is, more than 30 times stronger than the reported value for gold nanoparticles of the same size. Figure 2. Escape velocity measurements to quantify the trap stiffness for HeLa cells with and without lanthanide-doped nanoparticles. In conclusion, this study discovered that highly doping lanthanide ions in single nanoparticles can generate a strong oscillation resonance effect in the electromagnetic field and thereby substantially enhance the optical trapping force. This strategy can bypass the limitation set by the refractive index mismatch between an object and its surrounding medium, suggesting a new way to design far-field optical tweezers on the nanoscale. Also, benefiting from the limited heat generation, compared with gold nanoparticles, this work opens the door to a highly efficient, long-term, optical manipulation of biological samples. Furthermore, lanthanide-doped nanoparticles can be designed to be responsive to the surrounding temperature and pH values, and to enable multimodal manipulation. Mr. Xuchen Shan from the UTS Institute for Biomedical Materials & Devices (IBMD) was the lead author of the paper. Dr. Fan Wang of UTS, Dr. Peter J. Reece of the University of New South Wales (UNSW Sydney), and Prof. Dayong Jin of SUSTech and UTS, are the corresponding authors. The scholars acknowledge financial support from a UTS Chancellor’s Postdoctoral Research Fellowship, Australian Research Council (ARC) DECRA fellowship, the ARC Discovery Project, the National Natural Science Foundation of China (NSFC), Science and Technology Innovation Commission of Shenzhen, and the Australia–China Science and Research Fund Joint Research Centre for Point-of-Care Testing. Paper link: https://www.nature.com/articles/s41565-021-00852-0
Co-founder and President of Beijing Genome Institute (BGI), Dr. Wang Jian, along with Dr. Yu Hao , supervisor of the BGI group Board Office visited the SUSTech Department of Biomedical Engineering (BME SUSTech) on the 7th of December evening. Assoc. Professor Chen Fangyi, Assoc. Professor Likai, Asst. Professor Guo Qiongyu, Asst. Professor Ho Chun Loong, Asst. Professor Liu Chao and Miss Deng Dandan were in attendance to welcome the BGI entourage, aiming to foster closer collaborative ties through the many research projects that are ongoing in the various laboratories. President Wang highlighted the various potential collaborative work in multi-omic analysis with key foci on proteomic, metagenomic, and transcriptomic analysis. The multi-omic research provides tools to help further propel the development and later commercialization of the technologies established in BME SUSTech. President Wang emphasized his intent to further contribute to the Pearl Delta region’s growth and research advancement through closer collaboration with SUSTech. Preliminary discussions include many key research work within the department’s main research areas, including mechanomedicine, multiscale/multimodal biomedical imaging, wearable devices and wireless monitoring, biomedical MEMS, de novo regenerative engineering, computational medicine for big data, and health informatics. This BGI-BME SUSTech visit embodies both parties’ commitment to the continual collaboration to thrust the technological development and nurturing of specialized-trained workforce within the region. The BGI-BME SUSTech visit. (from left to right: Assoc. Professor Likai, Asst. Professor Guo Qiongyu, President Wang Jian, Asst. Professor Liu Chao, Assoc. Professor Chen Fangyi, Asst. Professor Ho Chun Loong) President Wang Jian (second from the right) and Dr. Yu Hao (center) explaining BGI’s latest technological advancement to the members of SUSTech BME. Asst. Professor Ho Chun Loong explaining his research work to President Wang Jian and Dr. Yu Hao during their visit to his laboratory. Reported by DENG Dandan
The study of organelles’ dynamics and their interactions have been limited by optical diffraction. Recently, teams from the Chair Prof. Dayong Jin at SUSTech and Prof. Xi Peng (Peking University) successfully created a super-resolution “street view” of intracellular organelles’ interactions and has this published in Nature Communications. This is the first time that researchers get the dynamics of lipid heterogeneity inside subcellular organelles with optical imaging technology. They have developed a Spectrum and Polarization Optical Tomography (SPOT) technique, which can resolve the membrane morphology, polarity, and phase from the intensity, spectrum, and polarization, respectively. Combined with lipophilic probes, the team successfully revealed more than ten types of organelles simultaneously and analyzed their sophisticated lipid dynamics. A cell is a self-efficient “micro-world” with various organelles responsible for nutrition import, metabolism, endocrine modulation, protein manufacturing, waste transportations, and all the efficient communications. The study of organelles’ dynamics and their interactions will help us understand the cell functions and diagnose the cause of diseases, as well as develop potential drug treatments. As widely-used fluorescence microscopy has limits in the color and type of fluorescent dyes and in temporal and spatial resolutions, it is extremely difficult to get simultaneous imaging of multiple organelle species. Lipid membranes in subcellular compartments synergistically regulate biophysical membrane properties, membrane protein function, and lipid-protein interactions. Despite its significant role in biochemical function and interaction of subcellular organelles, due to their similar chemical composition, it is challenging to study the classification and interaction of different types of lipid membranes and observe their dynamics for a long time. Compared with the other existing fluorescence microscopy techniques, SPOT is superior in optical throughput that correlatively obtains the high-dimensional information from six raw images within tens of milliseconds. SPOT’s optical section ability improves the measurement accuracy of polarity and phase. This is the first time that researchers quantitatively study the lipid heterogeneity inside subcellular organelles. Figure 1 Heterogeneity of subcellular lipid membranes revealed by SPOT. With SPOT, the lipid heterogeneity on the outer membrane and the cristae of mitochondria, as well as lipid dynamics through endosome maturation, can be clearly imaged in real-time. With the new imaging platform established at SUSTech, researchers observed the multi-organelle interactive activities of cell division, lipid dynamics during the plasma membrane separation, tunneling nanotubules formation, and mitochondrial cristae dissociation. Figure 2 Time-lapse high-dimensional super-resolution imaging of the late-stage division of two U2-OS cells Figure 3 Dynamic changes of lipid membrane during mitochondrial cristae dissociation Most microscopes can only image four or fewer color channels, far less than the types of intracellular organelles. The synergistic use of membrane morphology, lipid polarity, and the lipid phase can classify more than ten types of organelles. SUSTech Research Assistant Professor Karl Zhanghao is the co-first author and the co-corresponding author of the work. His contribution includes: (1) Super-resolution Dipole Orientation Mapping (SDOM) technique, (Light: Sci. Appl. 2016, https://doi.org/10.1038/s41467-019-12681-w, highlighted by Nat. Methods, https://doi.org/10.1038/nmeth.4061); (2) polarized Structured Illumination Microscopy (pSIM) technique, (https://10.1038/s41467-019-12681-w, highlighted by Nat. Methods, https://doi.org/10.1038/s41592-019-0682-6); (3) pSIM with improved imaging resolution (Opt. Express, https://doi.org/10.1364/OE.395092), and low-cost SIM with laser interference and digital micro-mirror device (Appl. Phys. Lett. 2020, https://doi.org/10.1063/5.0008264). Doctoral students Wenhui Liu from Tsinghua University, and Meiqi Li from Peking University are the co-first authors of this work. This work has been supported by the National Natural Science Foundation of China, National Key Research and Development Program of China, Beijing Natural Science Foundation, and Shenzhen Science and Technology Program. Article Link：https://doi.org/10.1038/s41467-020-19747-0
Chen HANG, Ran XIAO | 10/27/2020 27 Researchers from Southern University of Science and Technology (SUSTech) and Fuwai Hospital of the Chinese Academy of Medical Sciences ( referred to as “Fuwai Hospital”) have developed electronic blood vessels that can be actively tuned to address subtle changes in the body after implantation. The research, published in the journal Matter, entitled “Electronic Blood Vessel.” By using poly(L-lactide-co-ε-caprolactone) (PLC), the electronic blood vessels are made to encapsulate liquid metal to achieve the flexible and biodegradable circuit. It could also overcome the limitations of conventional tissue-engineered blood vessels (TEBVs), which serve as passive scaffolds., This could be achieved by coordinating with other electronic devices to deliver genetic material, enable controlled drug release, and facilitate the formation of new endothelial blood vessel tissue. The electronic blood vessels could integrate flexible electrons with three layers of blood vessel cells to imitate and surpass natural blood vessels. It can effectively promote cell proliferation and migration in the wound healing model through electrical stimulation. It can controllably deliver genes to specific parts of the blood vessel through electro-transfection. Through a 3-month in vivo study of the rabbit carotid artery replacement model, the authors evaluated the electronic blood vessel’s efficacy and biological safety in the vascular system. They confirmed its patency through ultrasound imaging and angiography. The research paves the way for the integration of flexible, degradable bioelectronics into the vascular system, which can be used as a platform for further treatments, such as gene therapy, electrical stimulation, and electronically controlled drug release. Electronic blood vessels show the potential to play a key role in the treatment of cardiovascular disease. In the treatment of cardiovascular disease through coronary artery bypass grafting, the existing small diameter (<6 mm) tissue-engineered blood vessels (TEBV) have not yet met clinical needs. The methods used in most studies only provide TEBV with a stent that provides mechanical support, which mainly relies on the remodeling process of host tissues but has obvious limitations in helping to regenerate new blood vessels. Specifically, the complex interaction between blood flow and TEBV usually causes resonance reactions, leading to problems such as thrombus formation and neointimal hyperplasia. Instead, the new generation of TEBV should have enough apical stents to provide mechanical support and the ability to respond and integrate with the remodeling process actively to provide adaptive treatment after implantation. In Situ Monitoring of the Electronic Blood Vessel (A) Schematic of the electronic blood vessel in the carotid artery of the rabbit. (B and C) An end-to-end anastomosis procedure of electronic blood vessel implantation in carotid arteries of rabbits (n = 6). The dotted frames (B and C)outline the margin of the native carotid artery and the implanted electronic blood vessel. The white arrows (C) indicate the two ends of the electronic blood vessel. Scale bar, 1 cm. (D–G) In situmonitoring of the electronic blood vessel by Doppler ultrasound imaging 3 months post-implantation. Representative images from at least three different animals. (D and E) The real-time blood flow at the operational site and the synchronized ultrasound pulses. The asymmetric velocity curve indicates that the signal is from the carotid artery rather than the vein. (E) Zoom-in view of red box in (D). (F) The cross-sectional view of the blood flow. (G) The suture site (red arrows) connecting the native carotid artery and the electronic blood vessel. (H) The diameter changes in the electronic blood vessel at different times post-implantation. (I) The velocity of blood flow at the operational site (n = 18, from different rabbits at different time points). (J and K) In situ monitoring by arteriography 3months post-implantation. (J) Image before injecting the contrastmedium. Red box indicates the position of the implanted electronic blood vessel. Scale bar, 1 cm. (K) Image after injecting the contrast medium. Red box indicates the position of the implanted blood vessel. Red arrows indicate the suture sites connecting the native carotid artery and the electronic blood vessel. Scale bar, 1 cm. The team uses a PTFE mandrel, forming a 3D multi-layered tubular structure with PLC-based metal-polymer conductor (MPC) membranes. The inner diameter of the electronic blood vessel is about 2 mm, which is flexible and degradable. The MPC circuit has excellent conductivity and can be well distributed in the three-dimensional multilayer tubular structure. Studies have found that electronic blood vessels also have excellent cell safety, including the three cultured vascular cells (human umbilical vein endothelial cells, human aortic smooth muscle cells, and human aortic fibroblasts). The team also constructed a 3D electrical function model to stimulate endothelial cells in vitro through electrochemical workstations to promote their proliferation and migration. Simultaneously, three kinds of blood vessel cells were patterned on the 3D electronic blood vessel, and the GFP plasmid was electroporated in vitro by an electroporation instrument. After two days of culture, the expression of the plasmid was observed. The team chose rabbits from New Zealand as the animal model, replacing the common carotid artery with electronic blood vessels. The implanted electronic blood vessels were monitored by Doppler ultrasound imaging and arteriography. According to Doppler ultrasound imaging, three months after implantation, the electronic blood vessel allows stable blood flow to pass, showing the electronic blood vessel’s excellent patency. In the future, the electronic blood vessel can be integrated with other electronic components and devices to achieve diagnostic and therapeutic functions. This will enhance significantly personalized medical functions by establishing a direct connection in the blood vessel tissue-machine interface. Shiyu Cheng, Chen Hang, and Li Ding are the joint first authors of the paper, and Yan Zhang (Fuwai Hospital) and Xingyu Jiang (SUSTech)are the corresponding authors. Link to the paper: https://www.sciencedirect.com/science/article/pii/S2590238520304938
Chris Edwards | 10/03/2020 40 Optical imaging has emerged as one of the promising imaging techniques in both research and clinical practice. Photoacoustic imaging and fluorescent imaging are the two leading representatives of optical-related imaging approaches. Their imaging qualities highly rely on contrast agents. The ideal photoacoustic and fluorescent agent is still to be found. The theoretical system that guides the construction of efficient contrast agents has not been widely established. Associate Professor Kai Li (Biomedical Engineering – BME) teamed up with several research teams. They have made significant progress in designing near-infrared two-zone imaging materials and biomedical diagnosis. Their research outcomes have been published in Angewandte Chemie International Edition (Angew Chem Int Ed), Biomaterials, and Research. The teams verified their design concepts and strategies through theoretical calculations. They obtained various high-performance photoacoustic and fluorescent imaging materials with optical activity in the second near-infrared window (NIR-II, 1000-1700 nm). They have applied them in different research fields, such as vascular imaging and tumor detection. The first paper at Angew Chem Int Ed. was titled “An Ester‐substituted Semiconducting Polymer with Efficient Nonradiative Decay Enhances NIR‐II Photoacoustic Performance for Monitoring of Tumor Growth.” The research teams synthesized several thiadiazoloquinoxaline (TQ)-based semiconducting polymers (SPs) with a broad absorption covering the NIR-I to NIR-II regions. The excited s-BDT-TQE shows a large dihedral angle, narrow adiabatic energy, and low radiative decay. It is attributed to the strongly electron-deficient ester-substituted TQ-segment. The more vigorous molecular motions trigger higher reorganization energy. They yield an efficient photo-induced nonradiative decay. BDT-TQE SP-cored nanoparticles with twisted intramolecular charge transfer (TICT) exhibit a high NIR-II photothermal conversion efficiency (61.6%). They also exhibit the preferable PA tracking in-situ hepatic tumor growth for more than 20 days. The research teams proposed a new approach that adjusted the TICT effect in polymer chains for augmented PNRD property. It enhanced the photothermal conversion & photoacoustic performance for monitoring in-situ tumor growth in mice. BME masters student Menglei Zha is the co-first author, along with City University of Hong Kong (CityU) Dr. Xiangwei Lin and National Kaoshiung University of Science and Technology (NKUST), Professor Jen-Shyang Ni. Dr. Kai Li is a co-corresponding author of this paper, with CityU Professor Lidai Wang and NKUST Dr. Jen-Shyang Ni. The authors are grateful to the National Natural Science Foundation of China, Guangdong Innovative and Entrepreneurial Research Team Program, the Shenzhen Science and Technology Program, Research Grants Council of the Hong Kong Special Administrative Region, and Fundamental Research Funds for the Central Universities 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 their technical support. Figure 1. Improve the nonradiative transition efficiency of semiconductor polymers to achieve long-term real-time monitoring of tumor growth via NIR-II photoacoustic imaging The paper published in Biomaterials was titled, “Self-assembled AIEgen nanoparticles for multi-scale NIR-II vascular imaging.” It looked at how fluorogens with aggregation-induced emission (AIEgens) have been intensively explored in biomedical applications. One primary strategy to bring these hydrophobic AIEgens into the aqueous biological environment is to encapsulate them in nanoparticles with functionalized polymeric matrices. Most fluorophores are insoluble in water, requiring post-modification like amphiphilic polymer encapsulation. The traditional preparation of AIEgen nanoparticles is convenient. These methods are hard to fulfill the required uniform size and stable loading efficiency. The exploration of reliable strategies that can afford AIE nanoparticles with the above requirements with minimized batch-to-batch variation remains challenging. The research team designed amphiphilic AIEgens, built with a hydrophobic donor-acceptor-donor (D-A-D) core and hydrophilic polyethylene glycol (PEG) chain. These AIEgens can self-assemble into uniform nanoparticles with average sizes of ~35 nm, showing an emission maximum beyond 1000 nm and quantum yields (QYs) above 10%. The team used the bright AIE nanoparticles for multi-scale intravital vascular fluorescence imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) in mouse and rabbit models. Advanced AIE nanoparticles with efficient self-assembly strategies were constructed for angiography. The early stages of demonstration for the AIEgen nanoprobes for NIR-II imaging in large animal models (rabbits with an average weight of 3 kg) will inspire more research opportunities in designing advanced NIR-II probes and promoting the translational studies of this emerging imaging technique. BME doctoral student Yaxi Li and Shenzhen Institute of Advanced Technology (SIAT) Dr. Dehong Hu are the co-first authors. Dr. Kai Li and SIAT Dr. Hairong Zhang are the co-corresponding authors of this paper. This work was supported by the National Natural Science Foundation of China, Guangdong Innovative and Entrepreneurial Research Team Program, the Science and Technology Innovation Committee of Shenzhen Municipality, the Shenzhen key laboratory of ultrasound imaging and therapy, and CAS key laboratory of health informatics. 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. Figure 2. Self-assembly strategy to prepare aggregation-induced luminescence nanoprobes to achieve multi-scale NIR-II vascular imaging The paper published in Research was titled, “Centimeter-Deep NIR-II Fluorescence Imaging with Nontoxic AIE Probes in Non-Human Primates.” In biomedical fluorescence imaging, AIEgens plays an increasingly important role. However, there is still a lack of in-depth toxicological research and deep imaging evaluation in primate models. The research team studied the high intravenous injection dose of AIE probes, 30 times the standard clinical dosage in primate blood and histological analysis report. The results showed that the AIE probes were in the normal range after 35 days of metabolism in primates, which proved that the AIE probes were not biologically toxic. The research team also utilized the biological safety and high-brightness optical performance of the AIE probe. They successfully achieved a depth of 1.5cm blood vessel imaging in primates, breaking the current limit of near-infrared two-zone fluorescence imaging at the millimeter level. The two features of NIR-II AIE probes enable them to become promising fluorophore candidates for angiography and lymphadenopathy. They could pave the way to promote clinical translation of NIR-II AIE probes in human clinical trials. Dr. Kai Li is a co-corresponding author of this paper, with the Hong Kong University of Science and Technology (HKUST) Professor Ben Zhong Tang and SIAT Dr. Hairong Zheng. Additional contributions came from the National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital. Figure 3. The NIR-II AIE probe achieves high signal-to-noise ratio blood vessel imaging in primates with a depth of 1.5 cm The second paper published in Angew Chem Int Ed. was titled “Sub‐10 nm Aggregation‐Induced Emission Quantum Dots Assembled by Microfluidics for Enhanced Tumor‐Targeting and Reduced Retention in the Liver.” AIE dots (AIE dots) obtained by hybridization with phospholipids have been widely used in biomedical imaging. However, the particle size of the AIE dots prepared in this traditional method is usually larger than 25 nm. Due to the interception of the liver, spleen, and other organs, the ideal imaging effect is often difficult to obtain with such large AIE dots. The research team developed a microfluidic chip with a double spiral mixing pipe (pipe width 300 microns, height 60 microns) to prepare AIE nanoparticles. These are known as AIE quantum dots (QDs), separate from the larger AIE dots. AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane-penetrating peptides or other targeting molecules. NIR-II AIEgens were used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm3 and evade the liver more efficiently than AIE dots. The sub-10 nm organic AIE QDs were successfully synthesized in a microfluidic chip, showing better in-vitro and in-vivo solid-tumor imaging than AIE dots. These AIE QDs promises a pathway for efficient cell labeling and sensitive & precise detection of the tumor. The microfluidic method may help make a broad range of multi-function AIE molecules into sub-10 nm AIE QDs. They could have immense potential in diverse biological applications. Doctor Xuanyu Li from the University of the Chinese Academy of Sciences (UCAS) is the first author, and Menglei Zha is the co-first author. Dr. Kai Li is a co-corresponding author. Additional contributions came from the BME Microfluidic Research laboratory. The research teams thank the National Key R&D Program of China, the National Natural Science Foundation of China, the Chinese Academy of Sciences, the Guangdong Innovative and Entrepreneurial Research Team Program, the Science and Technology Innovation Committee of Shenzhen Municipality, and the Tencent Foundation through the XPLORER PRIZE 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. Figure 4. The new microfluidic synthesis strategy prepares sub-10 nm AIE QDs to reduce liver retention and enhance tumor targeting in tumor-bearing mice. Related links: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202010228 https://www.sciencedirect.com/science/article/pii/S0142961220306116 https://doi.org/10.34133/2020/4074593 https://onlinelibrary.wiley.com/doi/10.1002/anie.202008564
Chris Edwards | 09/09/2020 In recent days, Shenzhen Municipal Science, Technology, and Innovation Commission (STIC) Deputy Director Xuan QIU led a delegation to the Department of Biomedical Engineering (BME) at Southern University of Science and Technology (SUSTech). SUSTech University Council Chairperson Yurong GUO met with the STIC delegation, along with long-term distinguished visiting BME professor Daping WANG. At the meeting, SUSTech University Council Chairperson Yurong GUO said that SUSTech’s rapid and high-quality development is inseparable from the support of the city, the province, and the state. The ongoing support from STIC for SUSTech’s development highlights its continuing commitment to “research, innovation, and entrepreneurship.” It will focus on the development of its talent pipeline, the transformation of its technology, and global cooperation to continue to contribute to the progress of Shenzhen. STIC Deputy Director Xuan QIU affirmed the developments SUSTech and BME has made in recent years. She spoke about the policies to promote the development of the bioengineering and pharmaceutical industry in Shenzhen. She pointed out that the biological and life health industry is one of the most dynamic emerging industries in the world. Numerous advantages are available to SUSTech, so the ongoing scientific and technological work conducted at SUSTech would encourage the implementation of the strategic goals for regional development. SUSTech Acting Vice President Yusheng ZHAO and Office of Research Deputy Director Yi GONG introduced the major scientific progress of SUSTech and related research projects. BME head Xingyu JIANG spoke about the teaching and research achievements of the department. He said that it would continue to integrate world-class technologies with more robust cooperation with Shenzhen enterprises. Long-term distinguished visiting BME professor Daping WANG said that BME would continue to build several international exchanges and cooperation platforms. It will improve the level of international cooperation and exchange. They will conduct extensive scientific research exchanges and technology transformations for the city’s sustainable development.
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