New achievement of cooperation between Professor Guo Dongsheng and Professor Ding Dan of Nankai University: "biomarker replacement activation" supramolecular strategy applied to tumor targeted light diagnosis and treatment

Introduction photodynamic therapy is becoming one of the most important methods of tumor treatment because of its advantages of small trauma and simple operation However, the traditional photosensitizers lack of tumor targeting and have phototoxicity to normal tissues, which limits their clinical application How to improve the existing commercial photosensitizers, reduce their phototoxicity and improve the therapeutic effect is a very challenging problem In recent years, the use of active photosensitizers in photodynamic therapy has attracted the attention of researchers Recently, Professor Guo Dongsheng's research group of School of chemistry of Nankai University and Professor Ding Dan's research group of School of life sciences have made new breakthroughs in this research field (j.am Chem SOC., 2018, DOI: 10.1021 / JACS 8b02331) (refer to the end of the article for the interview contents of Professor Guo Dongsheng) Professor Guo Dongsheng's project composition was established in March 2015 At present, there are 1 Professor, 4 doctoral students and 4 master's students in the project group Relying on the National Key Laboratory of organic elements of Nankai University, the national 2011 Tianjin chemical industry collaborative innovation center and the Key Laboratory of the Ministry of Education of functional polymer materials The research group is mainly engaged in "supramolecular diagnosis and treatment based on calixarenes" Based on the design and synthesis of new water-soluble calixarene derivatives, the basic physical and chemical properties, such as molecular recognition and assembly, are emphatically investigated, and then they are applied to the field of biomedicine, including biosensor, regulatory protein structure / activity, transmembrane transport and supramolecular light diagnosis and treatment, so as to provide new solutions for the diagnosis and treatment of tumor and Alzheimer's disease and other major diseases Road Prof Guo Dongsheng , professor and doctoral supervisor of School of chemistry, Nankai University, currently Deputy Director of the Department of chemistry and director of the teaching and Research Office of physical chemistry, School of chemistry, Nankai University, supported by the National Science Fund for outstanding young scholars in 2013, was selected into the training plan of 100 young discipline leaders of Nankai University in the same year, and was selected into the young science and technology talents of Tianjin innovation talents promotion plan and the top young talents of Tianjin in 2014 To support the plan In 2015, he won the first prize of Tianjin Natural Science (the second adult) Professor Guo Dongsheng received his Ph.D from Nankai University in 2006, stayed in the same year to teach, and was promoted to Professor in 2013 In 2014, he went to the University of Bremen in Bremen, Germany as a DAAD visiting scholar for academic exchanges Professor Guo has been committed to the research of supramolecular chemistry of calixarenes He has published more than 80 papers in acc chem Res., chem SOC Rev., J am Chem SOC., angel Chem Int ed., adv.mater., chem SCI And has cited more than 3400 times He has made more than 20 academic reports at academic exchange conferences at home and abroad At present, he is the young editorial board member of China Chemical express, and the editorial board member of Frontier chemistry At the same time, he is invited to be the reviewer of Korean national research foundation, National Natural Science Foundation, natural science foundation of Hebei Province and a number of academic journals The frontier research achievement: "biomarker replacement activation" supramolecular strategy applied to tumor targeted light diagnosis and treatment group Guo Dongsheng of Nankai University has done a series of pioneering work in the field of supramolecular diagnosis and treatment based on calixarenes In 2016, they first proposed the strategy of building artificial light capture system by using macrocyclic amphiphilic assemblies, and developed spectral tunable luminescent nanomaterials (adv mater., 2016, 28, 7666-7671; chem Commun., 2017, 53, 392-395; mater Chem Front., 2017, 1, 1847-1852), which have important application prospects in biological imaging In 2017, they used amphiphilic calixarenes to activate cell transmembrane peptide transport, and constructed a labeling free fluorescence detection kinase method (angelw Chem Int ed., 2017, 56, 15742-15745), which has guiding significance and reference value for interface recognition and drug delivery of calixarenes assembly In 2018, with the deepening of the research work to supramolecular diagnosis and treatment, they constructed a supramolecular sensing system based on guanidine calixarene with the help of indicator replacement detection method, and realized the ultra sensitive and specific detection of tumor marker lysophosphatidic acid (chem SCI., 2018, 9, 2087-2091) On the basis of the previous work, the research team found that calixarenes can regulate the photophysical properties of dyes according to actual needs, and can respond specifically to tumor markers More importantly, amphiphilic calixarenes can easily self assemble into nano drug carriers This prompted them to think about how to use calixarene as an intelligent module of nanodrugs to achieve tumor selective imaging and targeted treatment The research team chose to start with photodynamic therapy, "non covalent" to improve the existing commercial photosensitizers, reduce their phototoxicity and improve the targeted treatment effect, and achieve the goal of integration of diagnosis and treatment In order to solve the above key scientific problems, they proposed a new strategy of biomarker displacement activation (BDA), which was successfully applied to in vivo tumor imaging and treatment through a project combination with Professor Ding Dan, School of life sciences, Nankai University Starting from the mature commercial photosensitizers, the nano supramolecular drugs were constructed by the combination of supramolecular main body and photosensitizer and the interaction between the host and guest When the photosensitizer is encapsulated in the main cavity, its fluorescence imaging ability and photoactivity are completely quenched, so the photosensitizer is in a "silent" state in the process of drug delivery When the nanodrug is transported to the tumor tissue area, the over expressed biomarker will be combined with the main body, the photosensitizer will be replaced out of the cavity, and its original photophysical properties will be reactivated, so as to realize tumor selective imaging and targeted treatment (Fig 1) Compared with the covalent modification of photosensitizers, BDA strategy has the following advantages: (1) direct use of commercial photosensitizers to avoid cumbersome synthesis and separation; (2) photosensitizers are "traceless" released, and their photophysical properties remain high fidelity; (3) ）The amphiphilic assembly of calixarenes, as a drug loading platform, is versatile and can be adapted to a variety of photosensitizers according to actual needs Figure 1 Schematic diagram of "biomarker replacement activation" strategy (source: J am Chem SOC., 2018, Doi: 10.1021/jacs.8b02331) in order to verify the feasibility of BDA concept, the author designed guanidine modified amphiphilic calixarenes and constructed nano drug carriers Four representative commercial photosensitizers were selected as model drugs, and tumor markers were locked into adenosine triphosphate (ATP) (Figure 2a) When the photosensitizer is loaded on the calixarene nano carrier, its fluorescence and photoactivity are completely quenched When ATP concentration is tumor concentration, photosensitizer is competitive, fluorescence and photoactivity almost completely recover; however, ATP concentration in normal tissue does not cause photosensitizer leakage (Fig 2B, c) Figure 2 (a) schematic diagram of BDA based nanodrug implementation; and (b) (c) fluorescence and singlet oxygen response of photosensitizer, respectively (source: j.am Chem SOC., 2018, DOI: 10.1021/jacs.8b02331) further, the author expanded the BDA strategy based nanodrugs to antitumor in vivo They injected nanodrugs loaded with photosensitizer (alpcs 4) into nude mice via tail vein, and then performed real-time fluorescence imaging As shown in Fig 3, nanodrugs can target and release photosensitizers at tumor sites, achieving the purpose of tumor selective imaging Figure 3 Effect of BDA based tumor targeting imaging of nanodrugs in vivo (source: j.am Chem SOC., 2018, Doi: 10.1021/jacs.8b02331) then, according to the results of in vivo imaging, the author selected the best time point for photodynamic therapy, and the results showed that compared with the single commercial photosensitizer, the activated intelligent nano drug has accurate targeting and superior anti-tumor effect (Figure 3) Figure 4 the effect of BDA based nanodrug photodynamic therapy in vivo (source: j.am Chem SOC., 2018, DOI: 10.1021 / JACS 8b02331) In summary, the author proposed a novel BDA strategy based on the concept of host-guest chemistry, realizing tumor selective imaging and targeted therapy By elaborately designing the main structure of calixarenes, and by virtue of its excellent recognition and assembly properties, a nano drug integrated with diagnosis and treatment was constructed and successfully applied in the anti-tumor in vivo This pioneering work provides new methods and materials for the realization of precision medicine This research achievement was recently published in Journal of the American Chemical Society (DOI: 10.1021 / JACS 8b02331) The authors of this paper are: Jiegao, Jun Li (co authored), Wen Chao Geng, Fang Yuan Chen, Xingchen Duan, zhe Zheng, Dan Ding, Interview with Professor Guo Dongsheng CBG information: Professor Guo, what is the opportunity for you to start your involvement in the field of supramolecular chemistry of calixarenes? Do you have a change of thinking in this field now? Professor Guo Dongsheng: my involvement in the study of calixarene supramolecular chemistry is purely "feudal marriage" (the order of parents, the words of matchmaker) At that time, my tutor, Professor Liu Yu, designated calixarene as my research direction of doctoral dissertation, and I jumped in and never changed for 18 years Moreover, my dedication to scientific research and my love for calixarenes have never changed I often jokingly call calixarene my scientific lover In this process, I also learned a lot: interest can be cultivated; attitude determines success or failure; justice rewards diligence, persistence is victory CBG information: what research results do you think are most valuable or proud of since the independent research work? Professor Guo Dongsheng: calixarene is applied to the diagnosis and treatment of diseases In the exploration of its biomedical function, the charm of supermolecule and the characteristics of calixarenes are demonstrated CBG information: in the latest research results of the research team, what is the research idea? Professor Guo Dongsheng: due to the interdisciplinary nature of the research work of our research group, the current research ideas are: Based on organic synthesis, with the physical and chemical properties of molecular recognition and assembly as the core, and guided by the biomedical function It is hoped that in the next few years, breakthroughs will be made in the field of supramolecular diagnosis and treatment based on calixarenes, which will provide new methods and develop new materials for the realization of precision medicine 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, chembeango app, 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.