Adv. funct. Mater.: the team of academician Tang benzhong of Hong Kong University of science and technology has developed a dual functional AIE material that can be used to monitor and kill multidrug-resistant bacteria

Author: according to Li Ying's data, about 700000 people die of superbacterial infection every year in the world, and a large number of antibiotics are used The number of people who die of bacterial infection is still increasing More importantly, the multi drug resistance of bacteria caused by the abuse of antibiotics is becoming more and more common, which has become a major problem threatening human health in the future The development of new antibiotic therapy is one of the important strategies against super resistant bacteria, especially the new bactericidal mechanism, which has become a new hot spot in the development of new therapy for infection Due to its low background fluorescence, good biocompatibility and light stability, aiegen has been widely used to track physiological activities and changes in organisms and micro-organisms It has great potential in biomedical detection and analysis Especially in combination with the photodynamic activity of aiegen, the aggregation induced luminescence biomaterials have become a kind of integrated materials for diagnosis and treatment So, can antibiotics (drug sterilization) and AIE materials (fluorescence display and photodynamic therapy) be combined into one, so as to build a variety of antibiotic drugs with complementary sterilization mechanism, and can the mechanism of action of antibiotics and bacteria be traced by fluorescence, and the treatment mechanism can be explained to guide the development of new therapies? Recently, Professor Tang benzhong's team from Hong Kong University of science and technology, together with researcher Jiang Xingyu and researcher Zheng Wenfu from the national Nano Science Center, discussed this possibility Tripe-nt, a new aggregation induced luminescent antibacterial agent, was successfully prepared by combining tripe with AIE and NT It is found that tripe-nt has a typical aggregation induced luminescence (Fig 1) Figure 1 Characterization of structure and aggregation induced luminescence of tripe NT (source: adv funct Mater.) photodynamic therapy (PDT) uses photosensitizer (PSS) to absorb light and produce singlet excited state (S1) The energy of S1 state can be further transferred to triplet excited state (T1), which sensitizes peripheral triplet oxygen to produce singlet oxygen or other reactive oxygen species（ ROS) Compared with the traditional photosensitizers (porphyrins, etc.), aiegen's twisted molecular structure can avoid the singlet oxygen quenching caused by π - π stacking At the same time, aiegen with twisted intramolecular charge transfer (TICT) characteristics has been proved to effectively promote the production of ROS It was found that tripe-nt could produce ROS under white light by ROS indicator, and the fluorescence intensity of indicator increased about 70 times in 120 s As aiegen itself contains antibacterial group (NT), the author then tested whether tripe-nt's bactericidal effect and ROS generated by photodynamic can be superposed to enhance the bactericidal effect After tripe-nt treatment, the survival rates of E.coli (negative bacteria, G -), MDR E.coli (G -), Klebsiella pneumoniae (G -), MDR Klebsiella pneumoniae (G -), Staphylococcus epidermidis (positive bacteria, G +), MDR E 14.1%, 59.9%, 74.4%, 0%, 0%, 8.9% and 22.4% respectively; however, the survival rate of bacteria after 30 minutes of illumination was about 0%, 4%, 10%, 39%, 0%, 0%, 2% and 3%, respectively (Figure 2) The results showed that tripe-nt had bactericidal function and its bactericidal ability was significantly enhanced by light Figure 2 Light induced ROS production and tripe-nt antibacterial activity (source: adv funct Mater.) the author then studied the interaction between tripe-nt and bacteria FM TM 4-64fx (bacterial membrane) was co stained with tripe-nt It was found that in the same staining time, the amount of E.coli (G -) staining (adhering to the surface or entering the bacteria) was significantly less than that of S.epidermidis (G +) (Figure 3) This may be due to the negative charge on the surface of bacteria and the positive charge on the surface of tripe-nt Tripe-nt is easy to interact with bacteria However, due to the outer membrane of negative bacteria (G -) more than that of positive bacteria (G -), the amount of Escherichia coli (G -) entering into the cell wall is less than that of Staphylococcus epidermidis (G +) Figure 3 Open field and fluorescence imaging of tripe-nt interaction with bacteria (source: adv funct Mater.) in order to further verify the conjecture, the author first treated positive bacteria (Staphylococcus epidermidis, Staphylococcus MDR epidermidis, Staphylococcus aureus and Staphylococcus MDR aureus) and negative bacteria (Escherichia coli, MDR Escherichia coli, Klebsiella pneumoniae MDR Klebsiella pneumoniae) and then co stained with propidium iodide (PI, dead bacteria staining) The results showed that in the same time tripe-nt entered into the positive bacteria (G +) more than the negative bacteria (G -) and it was easier to kill the positive bacteria (Fig 4) There was a certain correlation between the number of bacteria killed and the amount of bacterial staining Figure 4 Bacterial staining and statistical analysis (source: adv funct Mater.) in order to further evaluate the antibacterial activity of tripe-nt in vivo, tripe-nt was used as an antibacterial spray to study the treatment of wounds infected by E The results showed that: on the third day, the wounds treated with tripe-nt healed faster than those untreated, and the difference was more obvious on the seventh day; on the seventh day, the wound healing rates of untreated E.coli, MDR E.coli, S.epidermidis and S.epidermidis MDR were about 16%, 11%, 34% and 29%, while those treated with tripe-nt were about 34% respectively , 28%, 83% and 65% This shows that tripe-nt can treat bacterial infected wounds, and wounds with positive bacteria heal faster than those with negative bacteria At the same time, the biocompatibility of the material in vitro (CCK-8) and in vivo (tissue section, he staining) was evaluated Figure 5 Tripe-nt in the treatment of bacterial infection wound (source: adv funct Mater.) conclusion: a new multifunctional aiegen antibacterial agent, tripe-nt, has been developed in this work, which is used to monitor drug bacterial interaction and in combination with photodynamic therapy (PDT) ）It can kill bacteria and enhance the antibacterial ability (white light, ROS production), and can effectively treat bacterial infection wounds The multi-functional design of the drug has the potential of comprehensive diagnosis and treatment in clinical practice, and the image analysis based on fluorescence provides an effective means to explain the mechanism of drug action These results provide a new idea for the next study of multidrug resistant bacteria This achievement was recently published in adv funct Mater (DOI: 10.1002 / ADFM 201804632) The authors of this paper are: Ying Li, Zheng Zhao, Jiang Zhang, Ryan K Kwok, Sheng Xie, Rongbing Tang, Yuexiao Jia, Junchuan Yang, Le Wang, Jacky W y Lam, Wenfu Zheng, * Xingyu Jiang, * Ben Zhong Tang * A review of previous reports by academician Tang benzhong: academician Tang benzhong of Hong Kong University of science and technology: aggregation induced emission, AIE) academician Tang benzhong of Hong Kong University of science and technology research group: simple multi-component polymerization method to prepare non-traditional light-emitting small heterocyclic polymer academician Tang benzhong of Hong Kong University of science and technology team: starting from aggregation induced light-emitting silver ion probe, Fluorescence silver staining and dynamic monitoring of silver ion release a new strategy for building deep red / near infrared AIE materials: smaller conjugated systems with longer absorption and emission wavelengths chem SCI: a new strategy for finding AIE materials from the natural world proposed by academician Tang benzhong of Hong Kong University of science and technology