Research group of Luo Liang, Professor of Huazhong University of science and technology: dual function and high efficiency photosensitizers for photodynamic therapy and real-time monitoring of anti-cancer effect

In the current cancer treatment, it is of great significance to develop a new treatment method with high efficiency and low toxicity, real-time monitoring of treatment effect and integrated diagnosis and treatment strategy At present, most of the reported diagnosis and treatment systems include a variety of different functional molecules in a drug loading system, such as nano carriers However, this method faces many problems, such as poor stability, low repeatability, and limited drug loading and release efficiency At present, most of the diagnosis and treatment systems focus on the reports of preoperative guidance and drug release behavior However, MRI and CT are often needed to evaluate the therapeutic effect It needs a waiting period of time for this evaluation method to observe the size of the tumor, which has little effect on the diagnosis of early treatment effect Once the treatment of the predetermined scheme fails, it may be too late to carry out the treatment of the second scheme, resulting in the missing of the best treatment time Therefore, it is a challenging problem to design a simple, efficient, low toxicity, and rapid monitoring of early treatment effect Recently, Professor Luo Liang and Associate Professor Meng Fanling of Huazhong University of science and technology, together with Professor Ding Dan of Nankai University and academician Tang benzhong of Hong Kong University of science and technology, have made new breakthroughs in this research field Relevant research results were published in adv funct Mater (DOI: 10.1002 / ADFM 201902673) Introduction to Professor Luo Liang's research group the main research directions of the research group are biomedical polymer materials, chemical biosensor materials and devices, nano pharmaceutical preparations and the inhibition and detection of amyloid protein In the past two years, a series of progress has been made in the preparation and application of photodynamic drugs and the research and development of new inhibitors of amyloid protein (adv funct Mater., ACS appl Mater Interfaces, bioconjugate chem., chem EUR J., ACS biomater SCI Eng., etc.), and more than 20 patents have been applied for Prof Luo Liang, selected by the youth "thousand talents plan" of the Central Organization Department, is currently a professor and doctoral supervisor of the school of life science and technology, National Center for nanodrug engineering and technology, HUST In 2009, he obtained a Ph.D in chemistry from Stony Brook University, New York State University, and conducted postdoctoral research in the Department of chemical materials, University of Minnesota from 2009 to 2012 From 2012 to 2015, he worked as a researcher in the R & D center of Bristol Myers Squibb pharmaceutical company, and served as the president of China US Pharmaceutical Development Association in Connecticut Cutting edge scientific research achievements: dual function and high efficiency photosensitizers used in photodynamic therapy and real-time monitoring of anti-cancer effect photodynamic therapy, as one of the new treatment methods with high efficiency and low toxicity, has attracted the attention of scientists The treatment and real-time monitoring of photodynamic therapy bring more application prospects to the development of photodynamic therapy The key elements of photodynamic diagnosis and treatment are photosensitizer and fluorescence report probe Photosensitizers are used to produce ROS and kill tumor cells, and then fluorescent molecules are used to report cell death Previously, it was reported that the combination of photosensitizer and fluorescent probe with caspase responsive polypeptide was used to evaluate the therapeutic effect, but this greatly increased the complexity and operation difficulty of the system and restricted its further application in animals (j.am.chem.soc 2011, 133, 18580; j.am.chem.soc 2014, 136, 2546; chem.commun 2015, 51, 8626) Therefore, Professor Luo Liang and Associate Professor Meng Fanling of Huazhong University of science and technology, together with Professor Ding Dan of Nankai University and academician Tang benzhong of Hong Kong University of science and technology, designed and synthesized a dual-function small molecule photodynamic therapy photosensitizer tpci, which can not only carry out efficient photodynamic therapy in vivo or in vitro, but also The real-time response to the treatment was achieved by the change of fluorescence Figure 1 Schematic diagram of tpci molecular synthesis and photodynamic diagnosis and treatment mechanism (source: adv funct Mater.) as a nonplanar structure containing three benzene ring rotors, triphenylamine is an effective group to construct aggregation induced luminescence molecules It has been reported that a series of organic small molecular structures, such as D - π - A, a - π - D - π - A, with triphenylamine as donor, have the ability of producing living oxygen under light and can effectively promote cell death The pyridine salt with positive charge in tpci can greatly increase the water solubility of the compounds, and has a good affinity with DNA Figure 2 ROS generation, DNA binding and photophysical properties of tpci (source: adv funct Mater.) photosensitizer tpci in aqueous solution has a singlet oxygen quantum yield of 98.6% Compared with commercial photosensitizer Bengal red, it has higher efficiency and better light stability In addition, tpci has a strong binding ability to DNA, and its binding constant is as high as 5.68 × 108m-1 When tpci binds to DNA, light can stimulate its aggregation induced fluorescence Figure 3 Tpci's phototoxicity experiment (source: adv funct Mater.) tpci's dark toxicity is weak, but tpci has a strong Photodynamic Killing Ability on a series of tumor cells In the case of very low luminous flux (460 nm, 4MW cm-2, 10 min), the IC 50 values of these tumor cells were not more than 300 nm But under the same conditions, tpci showed less phototoxicity to normal cells and showed better tumor cell selectivity Figure 4 Tpci can feed back the death of tumor cells at the same time of photodynamic therapy (source: adv funct Mater.) in the living cells, tpci is distributed in the cytoplasm, with weak fluorescence In the photodynamic process, the cells gradually die, and the permeability of nuclear membrane changes Tpci can successfully enter the nucleus and interact with the DNA in the nucleus The whole process only takes 15 seconds Figure 5 Photodynamic therapy and early monitoring of therapeutic effect in H22 bearing mice (source: adv funct Mater.) Figure 6 Photodynamic therapy and early monitoring of therapeutic effect in melanoma bearing mice (source: adv funct Mater.) finally, the author established two tumor bearing mice models (H22 hepatoma and b16h10 melanoma) ）To verify the photodynamic therapy and diagnosis effect The results show that tpci can not only effectively inhibit the growth of tumor in mice under photodynamic therapy, but also provide real-time feedback through the changes of fluorescence in tumor before and after treatment, which is of great significance for the early diagnosis of treatment Conclusion: tpci, as a dual-functional small molecule photosensitizer integrating photodynamic therapy and early diagnosis of therapeutic effect, has shown potential application prospects in photodynamic diagnosis and treatment, and provides a new paradigm for the design of multifunctional single molecule photodynamic diagnosis and treatment drugs This work was published on adv function Mater Doi: 10.1002/adfm.201902673) under the title of "a dual ‐ functional photosensor for ultra efficient photodynamic therapy and synchronousant anticoncer efficient monitoring" Gao Yuting, Ph.D., and Wang Xiuxia, Ph.D., from Huazhong University of science and technology, are co authors The corresponding authors are Luo Liang, Meng Fanling, Ding Dan, Nankai University and Tang benzhong, academician of Hong Kong University of science and technology This work was supported by the Ministry of science and technology, the National Natural Science Foundation of China and the China Postdoctoral Science Foundation Nowadays, people and scientific research have been paid more and more attention in the 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 group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.