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The use of antibiotic could cause severe drug-resistance and the increasing spread of pathogenic drug-resistant bacteria has brought a big threat to human health, hence, some innovative methods inspired, such as sonodynamic therapy, have become increasingly attractive for realizing the antibiotic-free methods against bacterial infection. However, many pathogens can invade normal healthy cells to establish intracellular replicative niches, which makes it more difficult to kill and remove these bacteria. Herein, inspired by respiratory mucus trapping bacteria to kill them, we developed a novel gel of amorphous TiOx nanofibers dotted with Ti2C(OH)2 nanosheets, which could capture and trap bacteria into the gel via a strong binding ability toward bacteria by forming a Ti–O–P bond between phosphate in the bacterial wall and Ti-OH in the gel, thereby, efficiently blocking the invasions of bacteria. Also, the gel has excellent ability for generating reactive oxygen species (ROS) under ultrasound irradiation, therefore, the bacteria in the gel could be effectively killed by the ROS produced under ultrasound irradiation. Moreover, Ti2C(OH)2 in the gel was able to scavenge H2O2, and transfer it into O2 in the infection environment, providing enough O2 for sonodynamic therapy. The experimental results have demonstrated that the functional gel obviously accelerated the healing of multidrug-resistant microorganisms-infected wounds.


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Sticking-bacteria gel enhancing anti-multidrug-resistant microbial therapy under ultrasound

Show Author's information Ya-Qi Zhu1Wei-Qiang Huang2Guang Chen2Lei Xia2Ye-Zi You2( )Yue Yu1( )
The Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China
Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, China

Abstract

The use of antibiotic could cause severe drug-resistance and the increasing spread of pathogenic drug-resistant bacteria has brought a big threat to human health, hence, some innovative methods inspired, such as sonodynamic therapy, have become increasingly attractive for realizing the antibiotic-free methods against bacterial infection. However, many pathogens can invade normal healthy cells to establish intracellular replicative niches, which makes it more difficult to kill and remove these bacteria. Herein, inspired by respiratory mucus trapping bacteria to kill them, we developed a novel gel of amorphous TiOx nanofibers dotted with Ti2C(OH)2 nanosheets, which could capture and trap bacteria into the gel via a strong binding ability toward bacteria by forming a Ti–O–P bond between phosphate in the bacterial wall and Ti-OH in the gel, thereby, efficiently blocking the invasions of bacteria. Also, the gel has excellent ability for generating reactive oxygen species (ROS) under ultrasound irradiation, therefore, the bacteria in the gel could be effectively killed by the ROS produced under ultrasound irradiation. Moreover, Ti2C(OH)2 in the gel was able to scavenge H2O2, and transfer it into O2 in the infection environment, providing enough O2 for sonodynamic therapy. The experimental results have demonstrated that the functional gel obviously accelerated the healing of multidrug-resistant microorganisms-infected wounds.

Keywords: multidrug-resistant bacteria, ultrasound, gel, bacteria-sticking

References(48)

1

Zhang, C. Y.; Gao, J.; Wang, Z. J. Bioresponsive nanoparticles targeted to infectious microenvironments for sepsis management. Adv. Mater. 2018, 30, 1803618.

2

Xin, Q.; Shah, H.; Nawaz, A.; Xie, W. J.; Akram, M. Z.; Batool, A.; Tian, L. Q.; Jan, S. U.; Boddula, R.; Guo, B. D. et al. Antibacterial carbon-based nanomaterials. Adv. Mater. 2019, 31, 1804838.

3

Qing, G. C.; Zhao, X. X.; Gong, N. Q.; Chen, J.; Li, X. L.; Gan, Y. L.; Wang, Y. C.; Zhang, Z.; Zhang, Y. X.; Guo, W. S. et al. Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection. Nat. Commun. 2019, 10, 4336.

4

Chellat, M. F.; Raguž, L.; Riedl, R. Targeting antibiotic resistance. Angew. Chem., Int. Ed. 2016, 55, 6600–6626.

5

Gao, W. W.; Zhang, L. F. Nanomaterials arising amid antibiotic resistance. Nat. Rev. Microbiol. 2021, 19, 5–6.

6

Wang, Y.; Yang, Y. N.; Shi, Y. R.; Song, H.; Yu, C. Z. Antibiotic-free antibacterial strategies enabled by nanomaterials: Progress and perspectives. Adv. Mater. 2020, 32, 1904106.

7

Zhao, H.; Huang, J.; Li, Y.; Lv, X. J.; Zhou, H. T.; Wang, H. R.; Xu, Y. Y.; Wang, C.; Wang, J.; Liu, Z. ROS-scavenging hydrogel to promote healing of bacteria infected diabetic wounds. Biomaterials 2020, 258, 120286.

8

Morgan, D. J.; Okeke, I. N.; Laxminarayan, R.; Perencevich, E. N.; Weisenberg, S. Non-prescription antimicrobial use worldwide: A systematic review. Lancet Infect Dis. 2011, 11, 692–701.

9

Jorgensen, I.; Zhang, Y.; Krantz, B. A.; Miao, E. A. Pyroptosis triggers pore-induced intracellular traps (PITs) that capture bacteria and lead to their clearance by efferocytosis. J. Exp. Med. 2016, 213, 2113–2128.

10

Fan, Y.; Li, X. D.; He, P. P.; Hu, X. X.; Zhang, K.; Fan, J. Q.; Yang, P. P.; Zheng, H. Y.; Tian, W.; Chen, Z. M. et al. A biomimetic peptide recognizes and traps bacteria in vivo as human defensin-6. Sci. Adv. 2020, 6, eaaz4767.

11

Yang, Y.; Wu, X. Z.; Ma, L.; He, C.; Cao, S. J.; Long, Y. P.; Huang, J. B.; Rodriguez, R. D.; Cheng, C.; Zhao, C. S. et al. Bioinspired spiky peroxidase-mimics for localized bacterial capture and synergistic catalytic sterilization. Adv. Mater. 2021, 33, 2005477.

12

Qian, X. Q.; Zheng, Y. Y.; Chen, Y. Micro/nanoparticle-augmented sonodynamic therapy (SDT): Breaking the depth shallow of photoactivation. Adv. Mater. 2016, 28, 8097–8129.

13

Huang, P.; Qian, X. Q.; Chen, Y.; Yu, L. D.; Lin, H.; Wang, L. Y.; Zhu, Y. F.; Shi, J. L. Metalloporphyrin-encapsulated biodegradable nanosystems for highly efficient magnetic resonance imaging-guided sonodynamic cancer therapy. J. Am. Chem. Soc. 2017, 139, 1275–1284.

14

Canavese, G.; Ancona, A.; Racca, L.; Canta, M.; Dumontel, B.; Barbaresco, F.; Limongi, T.; Cauda, V. Nanoparticle-assisted ultrasound: A special focus on sonodynamic therapy against cancer. Chem. Eng. J. 2018, 340, 155–172.

15

Han, X. X.; Huang, J.; Jing, X. X.; Yang, D. Y.; Lin, H.; Wang, Z. G.; Li, P.; Chen, Y. Oxygen-deficient black titania for synergistic/enhanced sonodynamic and photoinduced cancer therapy at near infrared-II biowindow. ACS Nano 2018, 12, 4545–4555.

16

Bilmin, K.; Kujawska, T.; Grieb, P. Sonodynamic therapy for gliomas. Perspectives and prospects of selective sonosensitization of glioma cells. Cells 2019, 8, 1428.

17

Li, C.; Yang, X. Q.; An, J.; Cheng, K.; Hou, X. L.; Zhang, X. S.; Hu, Y. G.; Liu, B.; Zhao, Y. D. Red blood cell membrane-enveloped O2 self-supplementing biomimetic nanoparticles for tumor imaging-guided enhanced sonodynamic therapy. Theranostics 2020, 10, 867–879.

18

Li, Z. Y.; Zhang, T. M.; Fan, F.; Gao, F.; Ji, H.; Yang, L. H. Piezoelectric materials as sonodynamic sensitizers to safely ablate tumors: A case study using black phosphorus. J. Phys. Chem. Lett. 2020, 11, 1228–1238.

19

Pan, X. T.; Wang, W. W.; Huang, Z. J.; Liu, S.; Guo, J.; Zhang, F. R.; Yuan, H. J.; Li, X.; Liu, F. Y.; Liu, H. Y. MOF-derived double-layer hollow nanoparticles with oxygen generation ability for multimodal imaging-guided sonodynamic therapy. Angew. Chem., Int. Ed. 2020, 59, 13557–13561.

20

She, J. L.; Zhou, X. F.; Zhang, Y. J.; Zhang, R.; Li, Q. G.; Zhu, W. J.; Meng, Z. Q.; Liu, Z. Thermo-triggered in situ chitosan-based gelation system for repeated and enhanced sonodynamic therapy post a single injection. Adv. Healthc. Mater. 2021, 10, 2001208.

21

Sun, L.; Xu, Y. R.; Zhang, X. M.; Gao, Y.; Chen, J. M.; Zhou, A. W.; Lu, Q. B.; Wang, Z. Y.; Shao, K. F.; Wu, H. M. et al. Mesenchymal stem cells functionalized sonodynamic treatment for improving therapeutic efficacy and compliance of orthotopic oral cancer. Adv. Mater. 2020, 32, 2005295.

22

Um, W.; Ko, H.; You, D. G.; Lim, S.; Kwak, G.; Shim, M. K.; Yang, S.; Lee, J.; Song, Y.; Kim, K. et al. Necroptosis-inducible polymeric nanobubbles for enhanced cancer sonoimmunotherapy. Adv. Mater. 2020, 32, 1907953.

23

Wang, X. W.; Zhong, X. Y.; Bai, L. X.; Xu, J.; Gong, F.; Dong, Z. L.; Yang, Z. J.; Zeng, Z. J.; Liu, Z.; Cheng, L. Ultrafine titanium monoxide (TiO1+x) nanorods for enhanced sonodynamic therapy. J. Am. Chem. Soc. 2020, 142, 6527–6537.

24

Zhang, D.; Lin, Z. G.; Zheng, Y. S.; Song, J. B.; Li, J.; Zeng, Y. Y.; Liu, X. L. Ultrasound-driven biomimetic nanosystem suppresses tumor growth and metastasis through sonodynamic therapy, CO therapy, and indoleamine 2,3-dioxygenase inhibition. ACS Nano 2020, 14, 8985–8999.

25

Zhu, P.; Chen, Y.; Shi, J. L. Piezocatalytic tumor therapy by ultrasound-triggered and BaTiO3-mediated piezoelectricity. Adv. Mater. 2020, 32, 2001976.

26

Yin, Y. F.; Jiang, X. W.; Sun, L. P.; Li, H. Y.; Su, C. X.; Zhang, Y.; Xu, G.; Li, X. L.; Zhao, C. K.; Chen, Y. et al. Continuous inertial cavitation evokes massive ROS for reinforcing sonodynamic therapy and immunogenic cell death against breast carcinoma. Nano Today 2021, 36, 101009.

27

Pang, X.; Liu, X.; Cheng, Y.; Zhang, C.; Ren, E.; Liu, C.; Zhang, Y.; Zhu, J.; Chen, X.; Liu, G. Sono-immunotherapeutic nanocapturer to combat multidrug-resistant bacterial infections. Adv. Mater. 2019, 31, 1902530.

28

Yue, W. W.; Chen, L.; Yu, L. D.; Zhou, B. G.; Yin, H. H.; Ren, W. W.; Liu, C.; Guo, L. H.; Zhang, Y. F.; Sun, L. P. et al. Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice. Nat. Commun. 2019, 10, 2025.

29

Gong, F.; Cheng, L.; Yang, N. L.; Gong, Y. H.; Ni, Y. W.; Bai, S.; Wang, X. W.; Chen, M. C.; Chen, Q.; Liu, Z. Preparation of TiH1.924 nanodots by liquid-phase exfoliation for enhanced sonodynamic cancer therapy. Nat. Commun. 2020, 11, 3712.

30

Guan, X.; Yin, H. H.; Xu, X. H.; Xu, G.; Zhang, Y.; Zhou, B. G.; Yue, W. W.; Liu, C.; Sun, L. P.; Xu, H. X. et al. Tumor metabolism-engineered composite nanoplatforms potentiate sonodynamic therapy via reshaping tumor microenvironment and facilitating electron–hole pairs’ separation. Adv. Funct. Mater. 2020, 30, 2000326.

31

Liang, S.; Deng, X. R.; Xu, G. Y.; Xiao, X.; Wang, M. F.; Guo, X. S.; Ma, P. A.; Cheng, Z. Y.; Zhang, D.; Lin, J. A novel Pt-TiO2 heterostructure with oxygen-deficient layer as bilaterally enhanced sonosensitizer for synergistic chemo-sonodynamic cancer therapy. Adv. Funct. Mater. 2020, 30, 1908598.

32

Wang, X. W.; Zhong, X. Y.; Gong, F.; Chao, Y.; Cheng, L. Newly developed strategies for improving sonodynamic therapy. Mater. Horiz. 2020, 7, 2028–2046.

33

Kalelkar, P. P.; Riddick, M.; García, A. J. Biomaterial-based antimicrobial therapies for the treatment of bacterial infections. Nat. Rev. Mater. 2022, 7, 39–54.

34

Wu, J. S.; Sha, J.; Zhang, C. L.; Liu, W. M.; Zheng, X. L.; Wang, P. F. Recent advances in theranostic agents based on natural products for photodynamic and sonodynamic therapy. View 2020, 1, 20200090.

35

Ouyang, J.; Tang, Z. M.; Farokhzad, N.; Kong, N.; Kim, N. Y.; Feng, C.; Blake, S.; Xiao, Y. F.; Liu, C.; Xie, T. et al. Ultrasound mediated therapy: Recent progress and challenges in nanoscience. Nano Today 2020, 35, 100949.

36

Ren, X. Y.; Huo, M. F.; Wang, M. M.; Lin, H.; Zhang, X. X.; Yin, J.; Chen, Y.; Chen, H. H. Highly catalytic niobium carbide (MXene) promotes hematopoietic recovery after radiation by free radical scavenging. ACS Nano 2019, 13, 6438–6454.

37

Sun, D.; Pang, X.; Cheng, Y.; Ming, J.; Xiang, S. J.; Zhang, C.; Lv, P.; Chu, C. C.; Chen, X. L.; Liu, G. et al. Ultrasound-switchable nanozyme augments sonodynamic therapy against multidrug-resistant bacterial infection. ACS Nano 2020, 14, 2063–2076.

38

Sun, S. D.; Song, P.; Cui, J.; Liang, S. H. Amorphous TiO2 nanostructures: Synthesis, fundamental properties and photocatalytic applications. Catal. Sci. Technol. 2019, 9, 4198–4215.

39

Li, J.; Yuan, X. T.; Lin, C.; Yang, Y. Q.; Xu, L.; Du, X.; Xie, J. L.; Lin, J.; Sun, J. H. Achieving high pseudocapacitance of 2D titanium carbide (MXene) by cation intercalation and surface modification. Adv. Energy Mater. 2017, 7, 1602725.

40

Huang, W. Q.; Wang, F.; Shen, A. Z.; Zhang, L.; Nie, X.; Zhang, Z.; Chen, G.; Xia, L.; Wang, L. H.; Ding, S. G. et al. Single nanosheet can sustainably generate oxygen and inhibit respiration simultaneously in cancer cell. Mater. Horiz. 2021, 8, 597–605.

41

Sang, X. H.; Xie, Y.; Lin, M. W.; Alhabeb, M.; Van Aken, K. L.; Gogotsi, Y.; Kent, P. R. C.; Xiao, K.; Unocic, R. R. Atomic defects in monolayer titanium carbide (Ti3C2Tx) MXene. ACS Nano 2016, 10, 9193–9200.

42

Deng, Y. Q.; Shang, T. X.; Wu, Z. T.; Tao, Y.; Luo, C.; Liang, J. C.; Han, D. L.; Lyu, R. Y.; Qi, C. S.; Lv, W. et al. Fast gelation of Ti3C2Tx MXene initiated by metal ions. Adv. Mater. 2019, 31, 1902432.

43

Lin, H.; Gao, S. S.; Dai, C.; Chen, Y.; Shi, J. L. A two-dimensional biodegradable niobium carbide (MXene) for photothermal tumor eradication in NIR-I and NIR-II biowindows. J. Am. Chem. Soc. 2017, 139, 16235–16247.

44

Lai, S.; Jeon, J.; Jang, S. K.; Xu, J.; Choi, Y. J.; Park, J. H.; Hwang, E.; Lee, S. Surface group modification and carrier transport properties of layered transition metal carbides (Ti2CTx, T: –OH, –F, and –O). Nanoscale 2015, 7, 19390–19396.

45

Shahzad, A.; Rasool, K.; Miran, W.; Nawaz, M.; Jang, J.; Mahmoud, K. A.; Lee, D. S. Two-dimensional Ti3C2Tx MXene nanosheets for efficient copper removal from water. ACS Sustainable Chem. Eng. 2017, 5, 11481–11488.

46

Nosaka, Y.; Nosaka, A. Y. Generation and detection of reactive rxygen species in photocatalysis. Chem. Rev. 2017, 117, 11302–11336.

47

Guo, Z. D.; Ambrosio, F.; Pasquarello, A. Hole diffusion across leaky amorphous TiO2 coating layers for catalytic water splitting at photoanodes. J. Mater. Chem. A 2018, 6, 11804–11810.

48

Wu, M. Q.; Zhang, Z. Y.; Liu, Z. R.; Zhang, J. M.; Zhang, Y. L.; Ding, Y. M.; Huang, T.; Xiang, D. L.; Wang, Z.; Dai, Y. J. et al. Piezoelectric nanocomposites for sonodynamic bacterial elimination and wound healing. Nano Today 2021, 37, 101104.

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Publication history
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Acknowledgements

Publication history

Received: 18 March 2022
Revised: 10 May 2022
Accepted: 16 May 2022
Published: 18 July 2022
Issue date: October 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was financially supported by the National Key Research and Development Program of China (No. 2020YFA0710700), the National Natural Science Funds for Distinguished Young Scholars (No. 51625305), the National Natural Science Foundation of China (Nos. 52131305, 52073269, 51873202, 22131010, 22101275, 81603339, 81602344, and 31870993), and the Fundamental Research Funds for the Central Universities (Nos. YD2060002016 and WK9110000005).

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