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Multidrug-resistant (MDR) bacterial infections are a pressing global public health problem
.
The development of alternative treatments and therapeutic drugs for MDR bacterial infections still faces many challenges
.
This is mainly due to a variety of reasons that lead to bacterial resistance, including the wide spread of drug resistance genes among strains, the reduction of effective drug concentrations by bacterial efflux pumps, poor antibiotic permeability, and the formation of bacterial biofilms
.
Photodynamic therapy (PDT) has the advantages of non-invasiveness, specific spatiotemporal selectivity, and low drug resistance, and has been considered as an effective strategy for the treatment of bacterial infections
.
The antibacterial properties of PDT largely depend on photosensitizers (PSs), which generate reactive oxygen species (ROS) upon light irradiation, thereby inactivating bacteria
.
In general, ROS can be divided into two categories: 1) Type I is the hydroxyl radical (•OH), superoxide anion radical (O2−•) and hydrogen peroxide (H2O2) generated during electron transfer; 2 ) Type II is the singlet oxygen (1O2) produced by the energy exchange process
.
Compared with the remarkable success of PDT in the clinical treatment of cancer, the clinical research progress of photodynamic antibacterial has been slow due to the lack of ideal photosensitizer drugs with bacterial targeting ability and low toxic side effects
.
Although some AIE photosensitizer-mediated antibacterial PDTs have been developed in recent years, the following problems still need to be addressed: (1) short absorption and emission wavelengths, low tissue penetration ability, and severe photodamage to biological systems; (2) ) poor imaging ability for Gram-negative (G−) bacteria, because the outer phospholipid membrane of G− bacteria cannot adequately limit the movement of AIE molecules; (3) the eradication efficiency of drug-resistant bacteria, especially drug-resistant bacteria, is low, This is mainly attributed to the limited kill radius and short lifespan of ROS
.
Figure 1 (A) Molecular structure of Type I AIE-PSs; (B) Type I and II photophysical chemical processes and imaging-guided photodynamic antibacterial applications
.
In response to the above problems, recently, Professor Wang Dong and Researcher Li Ying from the research group of Academician Tang Benzhong of Shenzhen University (Shenzhen University AIE Research Center) reported a series of efficient near-infrared aggregation-induced luminescence type I photosensitizers for imaging-guided photodynamic killing MDR bacteria (Figure 1)
.
Inspired by the introduction of cyano groups in the design of drug molecules to enhance the affinity with the target protein, based on the previous work of the research group (J.
Am.
Chem.
Soc.
2019, 141, 16781), the author creatively introduced the TTPy molecular structure cyano group, and ingeniously introduced heavy atoms such as Br and I through molecular engineering to construct a series of AIE photosensitizers with near-infrared emission
.
On the one hand, the introduction of cyano groups into the molecular structure can enhance the interaction with the outer phospholipid membrane of negative bacteria, and achieve broad-spectrum imaging of Gram-negative bacteria (G−) and positive bacteria (G+) by restricting molecular movement
.
On the other hand, cyano groups can act as acceptors to further enhance the donor-acceptor (DA) strength, which in turn greatly facilitates intramolecular charge transfer (ICT) as well as the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) The spatial separation of , leads to a decrease in the energy level difference (ΔEst) between the singlet state (S1) and the triplet state (T1)
.
At the same time, the heavy atom effect promotes the intersystem crossing (ISC) process, thereby inducing the generation of excited triplet states, which is beneficial to the generation of Type I reactive oxygen species
.
The results show that TTCPy series photosensitizers can efficiently generate type I hydroxyl radicals (•OH) and superoxide anion radicals (O2−•), and can achieve broad-spectrum bacterial imaging-mediated photodynamic therapy
.
It exhibits very efficient killing against methicillin-resistant Staphylococcus aureus (MRSA) and MDR E.
coli (MDR E.
coli) under white light irradiation
.
This research work provides a new idea for the development of next-generation near-infrared type I AIE photosensitizers
.
Figure 2 Molecular photophysical properties and reactive oxygen species of TTCPy series As shown in Figure 2, the maximum absorption peaks of TTCPy-1, TTCPy-2, TTCPy-3 and TTCPy-4 in DMSO are located at 532nm, 532nm, 534nm, and 534nm, respectively
.
The maximum emission peaks of TTCPy-1 and TTCPy-2 with hexafluorophosphate (PF6-) as counter ions in DMSO are 654 nm and 650 nm, respectively, and TTCPy-3 with bromine (Br-) and iodine (I-) as counter ions and TTCPy-4 emission maxima red-shifted to 748nm and 742nm
.
The test results of four reactive oxygen indicators, HPF, DHR123, SOSG and ABDA, showed that TTCPy series molecules mainly produced type I hydroxyl radicals and superoxide anion radicals
.
Figure 3 Antibacterial activity and bacterial morphological changes induced by TTCPy series photosensitizers The TTCPy series of molecules can show efficient photodynamic killing effect on MRSA, E.
coli, E.
coli Top 10 and MDR E.
coli
.
Finally, the author established a wound model of MRSA and MDR E.
coli infection in the back skin of rats (Figure 4), and selected TTCPy-3 with the best comprehensive performance to evaluate the photodynamic antibacterial effect
.
The experimental results showed that the wound healing speed of the photodynamic therapy experimental group was significantly higher than that of the blank group, especially the wounds infected with MRSA
.
The results of H&E, Masson and CD31 staining showed that on the 14th day of treatment, complete epidermis appeared in the new skin of the photodynamic therapy group, hair follicles and squamous epithelial cells were clearly visible on the wound tissue, and there were many new blood vessels and lumen.
The results show that TTCPy-3 has a good photodynamic therapy effect on wounds infected with drug-resistant bacteria
.
Figure 4 In vivo evaluation of TTCPy-3 on wounds infected with MDR E.
Coli and MRSA in rats Title, published in Advanced Science (DOI: 10.
1002/advs.
202104079)
.
This research work was supported by the National Natural Science Foundation of China (22007067, 22005195, 52122317, 22175120) and the General Program of China Postdoctoral Science Foundation (2020M672768)
.
WILEY paper information: Precise Molecular Engineering of Type I Photosensitizers with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Killing of Multidrug-Resistant BacteriaPeihong Xiao, Zipeng Shen, Deliang Wang, Yinzhen Pan, Ying Li*, Junyi Gong, Lei Wang , Dong Wang*, Ben Zhong Tang*Advanced ScienceDOI: 10.
1002/advs.
202104079Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal Advanced Science is a high-quality open-source journal founded by Wiley in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering
.
The journal is committed to maximizing the dissemination of scientific research to the public, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences are divided into the Q1 area of materials science and the Q1 area of engineering technology
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information to follow us and share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
.
The development of alternative treatments and therapeutic drugs for MDR bacterial infections still faces many challenges
.
This is mainly due to a variety of reasons that lead to bacterial resistance, including the wide spread of drug resistance genes among strains, the reduction of effective drug concentrations by bacterial efflux pumps, poor antibiotic permeability, and the formation of bacterial biofilms
.
Photodynamic therapy (PDT) has the advantages of non-invasiveness, specific spatiotemporal selectivity, and low drug resistance, and has been considered as an effective strategy for the treatment of bacterial infections
.
The antibacterial properties of PDT largely depend on photosensitizers (PSs), which generate reactive oxygen species (ROS) upon light irradiation, thereby inactivating bacteria
.
In general, ROS can be divided into two categories: 1) Type I is the hydroxyl radical (•OH), superoxide anion radical (O2−•) and hydrogen peroxide (H2O2) generated during electron transfer; 2 ) Type II is the singlet oxygen (1O2) produced by the energy exchange process
.
Compared with the remarkable success of PDT in the clinical treatment of cancer, the clinical research progress of photodynamic antibacterial has been slow due to the lack of ideal photosensitizer drugs with bacterial targeting ability and low toxic side effects
.
Although some AIE photosensitizer-mediated antibacterial PDTs have been developed in recent years, the following problems still need to be addressed: (1) short absorption and emission wavelengths, low tissue penetration ability, and severe photodamage to biological systems; (2) ) poor imaging ability for Gram-negative (G−) bacteria, because the outer phospholipid membrane of G− bacteria cannot adequately limit the movement of AIE molecules; (3) the eradication efficiency of drug-resistant bacteria, especially drug-resistant bacteria, is low, This is mainly attributed to the limited kill radius and short lifespan of ROS
.
Figure 1 (A) Molecular structure of Type I AIE-PSs; (B) Type I and II photophysical chemical processes and imaging-guided photodynamic antibacterial applications
.
In response to the above problems, recently, Professor Wang Dong and Researcher Li Ying from the research group of Academician Tang Benzhong of Shenzhen University (Shenzhen University AIE Research Center) reported a series of efficient near-infrared aggregation-induced luminescence type I photosensitizers for imaging-guided photodynamic killing MDR bacteria (Figure 1)
.
Inspired by the introduction of cyano groups in the design of drug molecules to enhance the affinity with the target protein, based on the previous work of the research group (J.
Am.
Chem.
Soc.
2019, 141, 16781), the author creatively introduced the TTPy molecular structure cyano group, and ingeniously introduced heavy atoms such as Br and I through molecular engineering to construct a series of AIE photosensitizers with near-infrared emission
.
On the one hand, the introduction of cyano groups into the molecular structure can enhance the interaction with the outer phospholipid membrane of negative bacteria, and achieve broad-spectrum imaging of Gram-negative bacteria (G−) and positive bacteria (G+) by restricting molecular movement
.
On the other hand, cyano groups can act as acceptors to further enhance the donor-acceptor (DA) strength, which in turn greatly facilitates intramolecular charge transfer (ICT) as well as the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) The spatial separation of , leads to a decrease in the energy level difference (ΔEst) between the singlet state (S1) and the triplet state (T1)
.
At the same time, the heavy atom effect promotes the intersystem crossing (ISC) process, thereby inducing the generation of excited triplet states, which is beneficial to the generation of Type I reactive oxygen species
.
The results show that TTCPy series photosensitizers can efficiently generate type I hydroxyl radicals (•OH) and superoxide anion radicals (O2−•), and can achieve broad-spectrum bacterial imaging-mediated photodynamic therapy
.
It exhibits very efficient killing against methicillin-resistant Staphylococcus aureus (MRSA) and MDR E.
coli (MDR E.
coli) under white light irradiation
.
This research work provides a new idea for the development of next-generation near-infrared type I AIE photosensitizers
.
Figure 2 Molecular photophysical properties and reactive oxygen species of TTCPy series As shown in Figure 2, the maximum absorption peaks of TTCPy-1, TTCPy-2, TTCPy-3 and TTCPy-4 in DMSO are located at 532nm, 532nm, 534nm, and 534nm, respectively
.
The maximum emission peaks of TTCPy-1 and TTCPy-2 with hexafluorophosphate (PF6-) as counter ions in DMSO are 654 nm and 650 nm, respectively, and TTCPy-3 with bromine (Br-) and iodine (I-) as counter ions and TTCPy-4 emission maxima red-shifted to 748nm and 742nm
.
The test results of four reactive oxygen indicators, HPF, DHR123, SOSG and ABDA, showed that TTCPy series molecules mainly produced type I hydroxyl radicals and superoxide anion radicals
.
Figure 3 Antibacterial activity and bacterial morphological changes induced by TTCPy series photosensitizers The TTCPy series of molecules can show efficient photodynamic killing effect on MRSA, E.
coli, E.
coli Top 10 and MDR E.
coli
.
Finally, the author established a wound model of MRSA and MDR E.
coli infection in the back skin of rats (Figure 4), and selected TTCPy-3 with the best comprehensive performance to evaluate the photodynamic antibacterial effect
.
The experimental results showed that the wound healing speed of the photodynamic therapy experimental group was significantly higher than that of the blank group, especially the wounds infected with MRSA
.
The results of H&E, Masson and CD31 staining showed that on the 14th day of treatment, complete epidermis appeared in the new skin of the photodynamic therapy group, hair follicles and squamous epithelial cells were clearly visible on the wound tissue, and there were many new blood vessels and lumen.
The results show that TTCPy-3 has a good photodynamic therapy effect on wounds infected with drug-resistant bacteria
.
Figure 4 In vivo evaluation of TTCPy-3 on wounds infected with MDR E.
Coli and MRSA in rats Title, published in Advanced Science (DOI: 10.
1002/advs.
202104079)
.
This research work was supported by the National Natural Science Foundation of China (22007067, 22005195, 52122317, 22175120) and the General Program of China Postdoctoral Science Foundation (2020M672768)
.
WILEY paper information: Precise Molecular Engineering of Type I Photosensitizers with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Killing of Multidrug-Resistant BacteriaPeihong Xiao, Zipeng Shen, Deliang Wang, Yinzhen Pan, Ying Li*, Junyi Gong, Lei Wang , Dong Wang*, Ben Zhong Tang*Advanced ScienceDOI: 10.
1002/advs.
202104079Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal Advanced Science is a high-quality open-source journal founded by Wiley in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering
.
The journal is committed to maximizing the dissemination of scientific research to the public, and all articles are freely available
.
The latest impact factor is 16.
806, and the 2020 SCI journals of the Chinese Academy of Sciences are divided into the Q1 area of materials science and the Q1 area of engineering technology
.
Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information to follow us and share cutting-edge information｜Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
