Research group of academician Tang benzhong of Hong Kong University of science and technology: self-report photosensitizers for in situ monitoring apoptosis process

Although photodynamic therapy (PDT) has been widely used as a promising cancer treatment method in the scientific community, high activity photosensitizers and strong light still have the risk of excessive treatment However, the additional diagnostic and therapeutic probes always make the non in situ monitoring process complicated and delayed How to monitor the response of photosensitizers in real time, reduce the side effects and improve the therapeutic effect is a challenging problem In recent years, researchers have paid more attention to the regulation of therapeutic effect by observing the process of apoptosis Recently, the research group of academician Tang benzhong of Hong Kong University of science and technology has made new breakthroughs in this field (J am Chem SOC., 2019, DOI: 10.1021/jacs.9b00636) Brief introduction to academician Tang benzhong, academician of the Chinese Academy of Sciences, member of the Royal Society of chemistry, Professor Zhang Jianquan, Department of chemistry and biomedical engineering, Hong Kong University of science and technology, Professor of South China University of technology, Guangzhou, honorary director of AIE Research Center, Shenzhen University At present, he is the chief scientist of the 973 Program of the Ministry of science and technology, the project director of the basic science research center of NSFC, the leader of the introduction and innovation research team of Guangdong Province, and the editor in chief of materials chemistry frontiers, a joint Journal of the Chinese Chemical Society and the Royal chemical society Professor Tang benzhong has published more than 1000 academic papers, which have been cited nearly 80000 times, with an H index of 131 He was successively selected as a highly cited scientist in the fields of chemistry and materials in 2014-2017 He has won a number of honors and awards, including the second National Natural Science Award, Croucher foundation Senior Researcher Award, Wang Baoren award of China Chemical Society, Feng Xinde award of Elsevier magazine, and he Liang and he Li Foundation Science and technology progress award In 2016, AIE nanoparticles were listed by nature as one of the four nanomaterials supporting the upcoming nano Light Revolution, and it is the only new material created by Chinese scientists In the same year, CNBC television in the United States conducted a live interview with Academician Tang on the theme of "year of cancer" to introduce the application of AIE fluorescent probes in cancer cell recognition and other fields to the global live broadcast; 2018 At the beginning of the year, he won the first prize of National Natural Science in 2017 with the "aggregation induced luminescence" project as the first project finisher Leading edge scientific research achievements: academician Tang benzhong of Hong Kong University of science and technology, a self-report photosensitizer for in-situ monitoring of apoptosis, has done a series of pioneering work in the development of aggregation induced emission (AIE) materials for evaluation of therapeutic response (chem - Asian J 2013, 8, 1806; J am Chem SOC 2014, 136, 2546 ) On the other hand, they constructed a series of red / near-infrared AIE photosensitizers for photodynamic cancer treatment (ACS Nano 2018, 12, 8145; adv mater 2018, 30, 1802105), which provided a new idea for the development of aggregation induced luminescence materials for biological treatment However, in order to evaluate its therapeutic response, additional commercial probes must be added, which greatly increases the complexity and operation difficulty of the system So far, no fluorescent material has been developed in the field of aggregation induced luminescence, which can monitor the response of photodynamic therapy in situ On the basis of previous work, the author developed an AIE photosensitizer with four positive charges, tpe-4ep +, which has high singlet oxygen production efficiency, and experienced the translocation from mitochondria to nucleus in the process of cell apoptosis induced by photodynamic therapy, so as to build a real-time self-report system to monitor the photodynamic therapy process in situ (Fig 1, j.am Chem Soc , DOI:10.1021/jacs.9b00636 ）。 Figure 1 Schematic diagram of a real-time self-report system for molecular design and in-situ monitoring of photodynamic therapy process (source: J am Chem SOC.) in order to achieve charge regulation of AIE materials, the author selected a typical AIE molecule tetraphenylethylene, TPE) as the core, different numbers of pyridines as positive charge units are connected on the TPE rotor, and AIE materials with two or three or four charges are synthesized Because of the long conjugated structure and the push-pull electron effect, all three molecules have long wavelength emission (610 nm) Fig 2 Fluorescence translocation of tpe-4ep + in light (source: J am Chem SOC.) during the exploration of its biological application, the author accidentally found that under continuous light, the fluorescence signal of tpe-4ep + with four charges would gradually transfer from mitochondria to nuclear area (Fig 2) At the same time, it is accompanied by the typical characteristics of cell apoptosis, such as cell volume contraction, cell membrane vesicles and morphological changes Figure 3 Annexin V / PI combined staining experiment (source: J am Chem SOC.) annexin V / PI double staining experiment further verified that tpe-4ep + transfer from mitochondria to nucleus did occur in the process of apoptosis (Figure 3) More importantly, tpe-4ep + can clearly distinguish different apoptosis stages Fig 4 Phototoxicity test inside and outside the molecular cell (source: J am Chem SOC.), followed by phototoxicity test inside and outside the cell for three AIE molecules (Fig 4) The results show that the three molecules have high singlet oxygen production efficiency and can effectively kill cancer cells under white light The experimental results also show that the singlet oxygen production efficiency and phototoxicity of tpe-2ep + < tpe-3ep + < tpe-4ep + Figure 5 Fixed cell staining experiment and DNA response test (source: J am Chem SOC.) finally, the author conducted fixed cell experiment and DNA response test The results showed that tpe-4ep + could specifically target the nucleus of the fixed cells and bind to DNA to enhance the fluorescence Based on the above experiments, the authors have made a reasonable explanation for the phenomenon of fluorescence transfer of tpe-4ep + in cells: in the process of apoptosis induced by photodynamic therapy, the mitochondrial membrane potential is lost, so that the charged tpe-4ep + gradually breaks away from the combination with the mitochondrial membrane; and because of the expansion of nuclear membrane permeability in the process of apoptosis, tpe-4ep+ Because of the electrostatic adsorption driving into the nucleus and combining with a large number of DNA in the nucleus and lighting up the nucleus, the fluorescence signal transfer from mitochondria to the nucleus area under photodynamic therapy is realized, and a real-time self-report system for monitoring the photodynamic therapy process in situ is constructed Conclusion: a new method of visual photodynamic therapy is developed by charge regulation of AIE molecules, which can effectively evaluate the therapeutic response, control phototoxicity and therapeutic time In addition, tpe-4ep's working principle can provide a strategy for the rational design of the new generation PS This work was published on j.am Chem SOC (DOI: 10.1021 / JACS 9b00636) under the title of "in situ monitoring apoptosis process by a self reporting photosensor" The first author is Dr Zhang Tianfu, Hong Kong University of science and technology, and Dr Li Yuanyuan is the co first author The corresponding author is Tang benzhong, academician of Hong Kong University of science and Technology (thesis author: Tianfu Zhang, Yuanyuan Li, Zheng Zheng, Ruquan ye, Yiru Zhang, Ryan T K Kwok, jackyw Y Lam, and Ben Zhong Tang) Review of previous reports: the latest JACS appreciation by academician Tang benzhong and Professor Ding Dan team: "unconventional" strategy: enhancing photothermal performance by enhancing molecular aggregation molecular motion Tang benzhong team of Hong Kong University of science and technology and Yu Xiaoqiang team of Shandong University: new ultra-low concentration AIE materials for specific two-photon lipid droplet imaging Academician Tang benzhong of Hong Kong University of science and technology and researcher Wang Shu of Institute of chemistry of Chinese Academy of Sciences Today, science and technology elements are increasingly valued in economic life, China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research groups, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit