Research group of Professor Bu Wenbo of East China Normal University: new progress of tumor chemokinetic therapy

As we all know, the microenvironment of tumor focus area has its own characteristics, such as acid (low pH), hydrogen peroxide rich, reducing (lack of oxygen) and so on It plays an extremely important role in tumor occurrence, development and metastasis, so it has attracted the attention of researchers At present, the research on nano materials for microenvironment response mainly focuses on the functional nano carriers responding to the controlled release of chemotherapy drugs in tumor microenvironment However, the inherent defects of chemotherapy still cannot be overcome If a new kind of functional material with good biocompatibility can be designed to replace the toxic chemotherapy drugs, and the internal microenvironment of tumor focus area can be used to realize the efficient treatment based on the specific activation of tumor microenvironment, then this kind of material will have important clinical potential Professor Bu Wenbo's research team, School of chemistry and molecular engineering, East China Normal University, and Shanghai Key Laboratory of green chemistry and chemical process greening, was inspired by the "Fenton reaction" principle of environmental science In 2016, a new concept of "chemokinetic therapy" (CDT) based on amorphous iron (angel Chem Int ed 2016, 55, 2101 – 2106) Since then, this new cancer treatment technology has developed rapidly, and many international research teams have made a series of research progress Recently, Professor Bu Wenbo was invited to publish a special review paper on tumor chemokinetic therapy "chemokinetic therapy: tumour microenvironment mediated Fenton and Fenton like reaction" (angel Chem Int ed., 2018, Doi: 10.1002/anie.201805664 Tang Zhongmin, doctoral student, is the first author of the paper, and Professor Bu Wenbo, tutor, is the corresponding author of the paper) In this review, the recent chemokinetic therapy of tumor was reviewed in three aspects: the selection of functional materials (iron-based, non-iron-based and organometallic framework materials), the regulation of tumor microenvironment (reducing pH, consuming glutathione and increasing hydrogen peroxide content), and the regulation of external energy field (light, electricity, magnetism, ultrasound and temperature) The latest progress, existing problems and development trend of Brief introduction to Professor Bu Wenbo's research group Professor Bu Wenbo joined the school of chemistry and molecular engineering of East China Normal University in 2016 and established the research group of rare earth biochemistry and medical functional materials The research group is mainly engaged in the research of rare earth multifunctional materials, including the research of chemical synthesis methods of new photoelectric magnetic functional materials, the research of optomagnetism, molecular imaging and high-efficiency diagnosis and treatment of diseases (tumors) of rare earth functional materials, and the research of new multifunctional materials used in Brain Science (brain neuroimaging and intelligent regulation) In the past five years, research work has focused on the structural design, chemical controllable synthesis and basic research of biomedical application of rare earth multifunctional materials, selected rare earth up conversion materials (ucnp) system, and focused on the key scientific issues of "efficient fusion of multimodal image and multi-functional therapy" of inorganic biomaterials Systematic innovations have been made in the design and preparation of rare earth functional materials: (1) the magnetic resonance imaging mechanism of ucnp inorganic image probe has been revealed, and a series of new multi-modal image probes based on ucnp have been constructed, realizing the efficient fusion and collaborative enhancement imaging of single probe structure image and functional image; (2) the rare earth functional materials of ucnp have been found“ The radiosensitization effect "proposed three kinds of material design strategies of" overcoming the lack of oxygen, using the lack of oxygen and avoiding the lack of oxygen ", which realized the high-efficiency treatment of the lack of oxygen tumor under the precise image-guided multi-functional collaborative enhancement; (3) proposed the new concept of" chemokinetic therapy ", expanded the use of inorganic functional materials in" tumor hunger therapy " The new idea realizes the high-efficient treatment based on the specific induction and activation of tumor microenvironment This series of research provides a new research idea to solve the bottleneck problems of clinical medicine, such as "low performance of conventional medical image probe, inherent defects of conventional tumor treatment technology (chemotherapy, radiotherapy)" Brief introduction to Professor Bu Wenbo, Professor (Level 2), doctoral supervisor of School of chemistry and molecular engineering, East China Normal University, winner of "National Fund for Distinguished Young Scholars" and young and middle-aged technological innovation leader of the Ministry of science and technology; part-time distinguished researcher of Shanghai Silicate Research Institute of Chinese Academy of Sciences, visiting professor of Huashan Hospital Affiliated to Fudan University In 2002, he obtained a doctor's degree from Nanjing University of technology In the same year, he joined Shanghai Silicate Research Institute of Chinese Academy of Sciences In 2005, he was promoted to associate researcher In 2008, he was exceptionally promoted to researcher In 2009, he was appointed as doctoral supervisor Since 2011, he has been deputy director of National Key Laboratory of high-performance ceramics and ultrastructure In 2016 He joined the school of chemistry and molecular engineering of East China Normal University as a distinguished professor in, and currently serves as the executive deputy director of Shanghai Key Laboratory of green chemistry and chemical process green, member of the third scientific research committee of East China Normal University and deputy director of the academic committee of the school of Chemistry In recent years, with the support of NSFC and Shanghai Science and Technology Commission, as the project leader, he has successively presided over and undertaken a number of national scientific research projects including seven NSFC (outstanding young scholars, special projects and general programs) As the backbone of the project, he participated in and completed many national scientific research projects, including "973 Plan", "863 Plan" and key projects of NSFC Since working independently in 2008, as the first author / corresponding author, he has published more than 50 research papers in NAT Nanotech., J am Chem SOC., angel Chem Int ed., adv mater And other international core SCI academic journals, and was invited to work in Chem Rev., chem SOC Rev., acc.chem Res, Coordin Chem Rev And other well-known academic journals have written many monographic review papers, with more than 6500 citations by SCI He has been selected (awarded) successively: National Fund for Distinguished Young Scholars (2017), young and middle-aged technological innovation leaders of Ministry of science and Technology (2017), Shanghai excellent academic leaders program (2016) In 2016, the outstanding graduate tutor award of the Chinese Academy of Sciences (2016), the Shanghai Youth Science and technology star tracking program (2012), the third nomination Award for Outstanding Youth Science and technology innovation talents of the Shanghai Branch of the Chinese Academy of Sciences (2012), the seventh round professional technology top talent award of Changning District of Shanghai (2010), the fifth Liu outline outstanding youth science and Technology Award (2008) In 2007), Shanghai Youth Science and Technology Star Program (2007), national defense science and technology second prize (2004) and other honorary titles Cutting edge research achievements: research team of Professor Bu Wenbo of East China Normal University has done a series of pioneering work in the field of tumor microenvironment specific treatment In 2016, they first proposed a new concept of "chemokinetic therapy" (CDT) based on amorphous iron (angel Chem Int ed 2016, 55, 2101 – 2106) The strategy is based on the logical response of acid dissociation and hydrogen peroxide disproportionation of amorphous iron nanoparticles in tumor microenvironment, which significantly improves the specificity of tumor treatment; CDT in situ produces hydroxyl radicals in tumor, leading to irreversible mitochondrial damage and DNA damage The chain break and the oxidation of protein and membrane do not need to apply external energy field, which avoids the limitation of light source tissue penetration depth and the side effects caused by radiotherapy X-ray It is worth mentioning that this kind of endogenous treatment strategy with logical response can effectively utilize tumor microenvironment, and the final product is biosafety iron ion, which avoids the potential toxicity of long-term retention of traditional drug carriers in vivo In 2017, they proposed for the first time to use the excellent photothermal conversion ability of FeS2 iron-based nanomaterials, which promoted the generation efficiency of hydroxyl radicals in chemokinetic therapy of FeS2, significantly improved the therapeutic effect of chemokinetic therapy, and realized the synergistic enhanced treatment of photothermal therapy and chemokinetic therapy (adv mater 2017, 29, 1701683) This research work puts forward the innovative idea of "self enhancement imaging and high-efficiency CDT treatment by using the specific response of variable valence element compounds to tumor microenvironment", which provides a reference for exploring the structural design of other materials used for high-efficiency CDT With the deepening of research work, how to further improve the efficacy of chemokinetic therapy has become an important issue In 2018, based on the principles of chemical kinetics, the research team focused on the selection of functional materials (iron-based, non-iron-based and organometallic framework materials), the regulation of tumor microenvironment (pH reduction The recent progress, problems and development trend of chemokinetic therapy for cancer were reviewed in this paper The first aspect is the selection of materials for chemokinetic therapy In Fenton reaction, ferrous ion plays a key role as catalyst Therefore, how to improve the release rate and quantity of ferrous ion in materials is very important Compared with crystalline iron, amorphous iron is easier to release a large number of ferrous ions in micro acid environment Therefore, amorphous iron can be used for high-efficiency chemical kinetic treatment In addition to iron-based nanomaterials, manganese dioxide can also stimulate Fenton like reactions in specific tumor microenvironment, so as to achieve the purpose of tumor treatment Similarly, metal organic framework (MOF) is an important branch of materials for chemokinetic therapy Figure 1 Amorphous iron and manganese dioxide for CDT (source: Angel W chem Int ed.) Figure 2 MOF material system for CDT (source: Angel W chem Int ed.) in the second aspect, tumor microenvironment regulation The authors point out that from the perspective of Fenton reaction conditions, how to reduce the pH of tumor microenvironment, increase the content of hydrogen peroxide and consume glutathione are also crucial From the perspective of endogenous tumor cells, gene regulation technology can be used to regulate the pH and hydrogen peroxide content in tumor cells, and achieve the purpose of reducing pH and increasing the content of hydrogen peroxide, so as to improve the effect of chemokinetic therapy From the point of view of exogenous, we can use the chemical reaction between the self-assembled nano materials and ascorbic acid in the tumor focus area to produce hydrogen peroxide efficiently, which can significantly enhance the Fenton reaction efficiency; in addition, we can also use the dendritic organosilicon to load glucose oxidase and tumor glucose Hydrogen peroxide can also promote Fenton reaction and increase the content of hydroxyl radicals Figure 3 RNA gene technology regulates pH and hydrogen peroxide content to optimize CDT effect (source: angelw Chem Int ed.) Figure 4 Self assembled nanomaterials react with ascorbic acid to produce hydrogen peroxide, thus improving CDT efficiency (source: angelw Chem Int ed.) Figure 5 Tree branches