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BIT Makes Achievements in "Cluster Luminescence" Spiral Polymers for Recognition and Diagnosis of Tumor Cells

release date :2020-03-03 10:24:00  |   [ close window ]ViewCount:

  Beijing Institute of Technology, Feb 25th, 2020: Tumor protein P53, is crucial in multicellular organisms, where it prevents cancer formation, and thus functions as a tumor suppressor protein. P53 plays a role in regulating and repairing DNA when it has sustained damage. And it can initiate apoptosis if cell damage proves to be irreparable, avoiding its infinite division under adverse conditions. In tumor cells, the expression and activity of P53 are often inhibited by the over-expression of MDM2 protein. The mechanism is that P53 can insert into hydrophobics of MDM2 (Trp26, Phe19, Leu26) and bind with them, so its physiological activity is negatively regulated. 

  Recently, supported by the National Natural Science Foundation of China (Grant No. 21490574) and General Program (Grant No.21474009 and No. 51673024), Dongping Ping's group at Beijing Institute of Technology(BIT) cooperated with Kim Jong Seung's group at Korea University. It is reported that through the combining of the over-expression of MDM2 protein in tumor cells and non-traditional conjugated spiral polymer, "cluster-triggered" emission was generated. At the same time, P53 is restricted to bind with MDM2 protein, which released and activated P53 protein. In this way, the apoptosis of cancer cells is promoted and the advance of related work in diagnosis and treatment of tumor cells has been made.

  Spiro compounds have good biological activity and stability due to their unique chemical structures and have been used in many drugs, such as Enilospirone, Buspirone, etc. However, the synthesis and application of spirocyclic polymers are rarely reported. In this work, a new type of spirocyclic polymer is first synthesized by the "non-catalytic, one-step" triple-bond based polymerization reaction. The experimental results show that the spiral polymer had typical Cluster Triggered Emission (CTE) characteristics. Under conditions in vitro, MDM2 protein could interact with the spiral polymer, which induce further aggregation of P1a2b and trigger cluster emission; Therefore, many tumor cells with over-expression of MDM2 present obvious blue fluorescence, but normal cells with low-expression of MDM2 protein do not present obvious luminescence. In this way, the imaging effect of high molecular weight P1a2b is more obvious and the difference between normal cells and tumor cells can be distinguished effectively. The author verifies the interaction site of the P1a2b spiral polymer in the cell through a competition experiment between MDM2’s inhibitor Nutlin-3 and P1a2b, and find that after the interaction of the MDM2 protein mixed with P1a2b and Nutlin-3, it could not present the characteristic of cluster-triggered emission. It shows that Nutlin-3 preferentially occupied the interaction site of MDM2 protein, causing P1a2b couldn’t effectively bind to it, so polymer clusters could not  aggregate and emit light.

Figure1: the synthetic route of Spiropolymers

Figure 2: (A) (B) (C) photos of DAPI, FITC without P1a2b polymer; (D) (E) (F) photos of DAPI, FITC with P1a2b polymer; (G) Apoptosis rate after co-culture with P1a2b polymer for 24 h, 48 h, and 72 h.

  Subsequently, the authors confirm that the expression of P53 protein in P1a2b co-cultured cells increased through “Western blot”. At the same time, it is proved that after the addition of P1a2b, the increase of P53 would lead to the increase of its related ROS’s concentration, which is the main reason why P1a2b polymer induced high apoptosis of tumor cells. At the same time, the author use softwares for molecular docking to calculate the P1a2b trimer and MDM2 protein, and confirm that it bound to Trp26, Phe19 and Leu26 hydrophobic cavities, and the binding is stable.

  In view of the spiral polymer’s simple synthesis and the ability to combine targeted diagnosis and treatment of tumor cells, it provides new ideas for the application of new spiral polymers and new methods for the treatment and diagnosis of tumors. Dr. Liu Pai and Dr. Fu Weiqiang are the co-first authors of this work. Cai Zhengxu is the specially-appointed researcher. Professor Dong Yuping, and Professor Kim Jong Seung are the corresponding authors.

  The paper has been published in Angewandte Chemie International Edition, the link is :


​Editor: News Agency of BIT 
Translator: Zhang Yinuo, News Agency of BIT

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