Research of Synergistic Photothermal Antibacterial Strategy Based on Polymeric Guanidine Derivative Grafted on Mesoporous Carbon Nanospheres

doi:10.6023/A21120548

Abstract

Bacterial infection is one of the major problems that seriously threaten people's life and health. In recent years, photothermal therapy (PTT), which uses photothermal conversion nanomaterials to convert optical energy into thermal energy for sterilization under specific wavelength laser irradiation, has aroused wide interest of researchers. Compared with traditional antibiotic therapy, the new anti-bacterial strategy photothermal therapy shows the excellent performance of controllable, minimally invasive and less bacterial resistance. However, monomodal PTT therapy is not ideal because it is often associated with side effects such as inflammatory reaction. Therefore, it is necessary to develop novel photothermal antibacterial system with high biocompatibility and safety to fight bacterial infection. Combined antibacterial strategy can effectively solve this problem. In this work, mesoporous carbon nanospheres (MCN) were prepared and oxidized by the mixed acid to obtain carboxyl-rich oxidized mesoporous carbon nanospheres (OMCN) with high biocompatibility and photothermal properties. Then, OMCN- PHMB nano-antibacterial platform was obtained by grafting the antimicrobial agent poly(hexamethylene biguanide)hydrochlo- ride (PHMB) onto the surface of OMCN with amide covalently. The photothermal properties of the system were evaluated and the results showed that the photothermal performance of OMCN had a good dependence on the concentration and power density of near-infrared light. Similar to the OMCN, the obtained OMCN-PHMB exhibited excellent performance of photothermal controllability and photothermal stability. In vivo and in vitro antibacterial experiments showed that the therapeutic effect of OMCN-PHMB under 808 nm laser irradiation was significantly better than that of other treatment groups under the single mode, which confirmed the excellent antibacterial effect of OMCN-PHMB combined with photothermal therapy. In addition, histological analysis showed that the nanoplatform had no significant toxicity to the major organs of mice, indicating OMCN-PHMB had a high biocompatibility. To sum up, the photothermal synergistic nano-antibacterial platform constructed in this study is expected to serve as a safe and controllable biomedical platform to combat various diseases caused by bacterial infection, providing a new antibacterial strategy for clinical treatment of bacterial infection diseases.

Key words: bacterial infection, photothermal therapy (PTT), poly(hexamethylene biguanide)hydrochloride (PHMB), combination therapy, antibacterial

Cite this article

Shen Zhang, Shan Feng, Longyu Ma, Yingying Yang, Chaoqun Liu, Ningning Song, Yanwei Yang. Research of Synergistic Photothermal Antibacterial Strategy Based on Polymeric Guanidine Derivative Grafted on Mesoporous Carbon Nanospheres[J]. Acta Chimica Sinica, 2022, 80(3): 265-271.

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Fig. & Tab. 7

Scheme 1. Schematic illustration of preparation process of OMCN- PHMB and its application in synergistic photothermal antibacterial therapy

Figure 1. SEM images of (a) MCN and (b) OMCN, XRD patterns of (c) MCN and (d) OMCN, (e) FTIR spectra of MCN, OMCN and OMCN-PHMB, (f) size distribution of MCN and OMCN, and (g) Zeta potential of MCN, OMCN and OMCN-PHMB

Figure 2. (a) UV-Vis-NIR spectrum of MCN and OMCN (Inset: photographs of MCN and OMCN dispersed in deionized water), (b) temperature changes of OMCN at different concentrations illustrated with an 808 nm laser (1.5 W/cm2) and (c) corresponding infrared thermal images, (d) temperature changes of OMCN (55 µg/mL) after irradiated by an 808 nm laser with different power intensities and (e) corresponding infrared thermal images, and (f) recycling-heating profiles of OMCN dispersion (55 µg/mL) irradiated for five on/off cycles (1.5 W/cm2)

Figure 3. (a) Photographs of S. aureus colonies on an LB agar plate after treated with PBS (pH 7.4), OMCN (55 µg/mL), PHMB (2.86 μg/mL) and OMCN-PHMB (55 µg/mL) with or without NIR irradiation (808 nm, 1.5 W/cm2, 10 min), (b) S. aureus urvival ratio for the different groups with or without laser irradiation (808 nm, 1.5 W/cm2, 10 min) [determined by measuring the optical density at 600 nm; Error bars represent the standard deviation (n=3). Asterisks indicate statistically significant differences ($\overline{x}$±s, *P<0.05, **P<0.01, ***P<0.001)], and (c) LIVE/DEAD fluorescent staining results of S. aureus after treated with PBS (pH 7.4), OMCN (55 µg/mL), PHMB (2.86 μg/mL) and OMCN-PHMB (55 µg/mL) with or without NIR irradiation (808 nm, 1.5 W/cm2, 10 min)

Figure 4. Cell viability of HL-7702 cells after incubation with different concentration of OMCN and OMCN-PHMB, respectively [Error bars represent the standard deviation (n=3)]

Figure 5. (a) Schematic diagram of infected wound formation in mice and the following treatments, (b) photographs of infected wounds after different treatments for 1, 3 and 5 d, (c) bacteria isolated from the mice wounds on day 5 and cultured on LB agar plates, (d) H&E-stained tissue slices from the wound areas of different groups on day 5, (e) quantitative analysis of bacterial colonies from tissues of different treatment groups, (f) quantitative analysis of relative wound area of different treatment groups on day 5, and (g) body weight variation among infected mice after different treatments for 1, 3 and 5 d [Error bars represent the standard deviation (n=3). Asterisks indicate statistically significant differences ($\overline{x}$ ±s, *P<0.05, **P<0.01, ***P<0.001)]

Figure 6. Histology analysis of major organs (heart, liver, spleen, kidney and lung) in different groups by H&E staining

References 40

[1]	Qiao, Y.; Ma, F.; Liu, C.; Zhou, B.; Wei, Q.; Li, W.; Zhong, D.; Li, Y.; Zhou, M. ACS Appl. Mater. Interfaces 2018, 10, 193. doi: 10.1021/acsami.7b15251
[2]	Sun, J.; Fan, Y.; Ye, W.; Tian, L.; Niu, S.; Ming, W.; Zhao, J.; Ren, L. Chem. Eng. J. 2021, 417, 128049. doi: 10.1016/j.cej.2020.128049
[3]	Chen, C.; Chu, G.; Qi, M.; Liu, Y.; Huang, P.; Pan, H.; Wang, Y.; Chen, Y.; Zhou, Y. ACS Appl. Bio Mater. 2020, 3, 9117. doi: 10.1021/acsabm.0c01343
[4]	Liu, C.; Feng, S.; Ma, L.; Sun, M.; Wei, Z.; Wang, J.; Chen, Z.; Guo, Y.; Shi, J.; Wu, Q. ACS Appl. Mater. Interfaces 2021, 13, 38029. doi: 10.1021/acsami.1c07399
[5]	Li, J.; Li, B.; Wang, J.; He, L.; Zhao, Y. Acta Chim. Sinica 2021, 79, 238. (in Chinese) doi: 10.6023/A20090441
	(李佳欣, 李蓓, 王纪康, 何蕾, 赵宇飞, 化学学报, 2021, 79, 238.) doi: 10.6023/A20090441
[6]	Shen, H.; Jiang, C.; Li, W.; Wei, Q.; Ghiladi, R. A.; Wang, Q. ACS Appl. Mater. Interfaces 2021, 26, 31193.
[7]	Yu, X.; He, D.; Zhang, X.; Zhang, H.; Song, J.; Shi, D.; Fan, Y.; Luo, G.; Deng, J. ACS Appl. Mater. Interfaces 2019, 11, 1766. doi: 10.1021/acsami.8b12873
[8]	Qi, Y.; Ren, S.; Che, Y.; Ye, J.; Ning, G. Acta Chim. Sinica 2020, 78, 613. (in Chinese) doi: 10.6023/A20040126
	(齐野, 任双颂, 车颖, 叶俊伟, 宁桂玲, 化学学报, 2020, 78, 613.) doi: 10.6023/A20040126
[9]	Li, J.; Wang, Y.; Yang, J.; Liu, W. Chem. Eng. J. 2021, 420, 127638. doi: 10.1016/j.cej.2020.127638
[10]	Guo, C.; Ma, X.; Wang, B. Acta Chim. Sinica 2021, 79, 967. (in Chinese) doi: 10.6023/A21040173
	郭彩霞, 马小杰, 王博, 化学学报, 2021, 79, 967.) doi: 10.6023/A21040173
[11]	Cao, F.; Ju, E.; Zhang, Y.; Wang, Z.; Liu, C.; Li, W.; Huang, Y.; Dong, K.; Ren, J.; Qu, X. ACS Nano 2017, 11, 4651. doi: 10.1021/acsnano.7b00343
[12]	Yan, T.; Liu, J. Acta Chim. Sinica 2020, 78, 713. (in Chinese) doi: 10.6023/A20050164
	(闫腾飞, 刘俊秋, 化学学报, 2020, 78, 713.) doi: 10.6023/A20050164
[13]	Yu, Y. T.; Shi, S. W.; Wang, Y.; Zhang, Q. L.; Gao, S. H.; Yang, S. P.; Liu, J. G. ACS Appl. Mater. Interfaces 2020, 12, 312. doi: 10.1021/acsami.9b18865
[14]	Geng, H.; Cui, J.; Hao, J. Acta Chim. Sinica 2020, 78, 105. (in Chinese) doi: 10.6023/A19080301
	耿慧敏, 崔基炜, 郝京诚, 化学学报, 2020, 78, 105.) doi: 10.6023/A19080301
[15]	Aksoy, I.; Kucukkececi, H.; Sevgi, F.; Metin, O.; Hatay Patir, I. ACS Appl. Mater. Interfaces 2020, 12, 26822. doi: 10.1021/acsami.0c02524
[16]	Wang, Y.; Zhu, D.; Yang, Y.; Zhang, K.; Zhang, X.; Lv, M.; Hu, L.; Ding, S.; Wang, L. Acta Chim. Sinica 2020, 78, 76. (in Chinese) doi: 10.6023/A19100371
	(王英美, 朱道明, 杨阳, 张珂, 张修珂, 吕明珊, 胡力, 丁帅杰, 王亮, 化学学报, 2020, 78, 76.) doi: 10.6023/A19100371
[17]	Yan, L. X.; Chen, L. J.; Zhao, X.; Yan, X. P. Adv. Funct. Mater. 2020, 30, 1909042. doi: 10.1002/adfm.v30.14
[18]	Liu, Y.; Guo, Z.; Li, F.; Xiao, Y.; Zhang, Y.; Bu, T.; Jia, P.; Zhe, T.; Wang, L. ACS Appl. Mater. Interfaces 2019, 11, 31649. doi: 10.1021/acsami.9b10096
[19]	Jiao, Y.; Zhang, X. Acta Chim. Sinica 2018, 76, 659. (in Chinese) doi: 10.6023/A18070273
	(焦阳, 张希, 化学学报, 2018, 76, 659.) doi: 10.6023/A18070273
[20]	Zhao, Y. Q.; Sun, Y.; Zhang, Y.; Ding, X.; Zhao, N.; Yu, B.; Zhao, H.; Duan, S.; Xu, F. J. ACS Nano 2020, 14, 2265. doi: 10.1021/acsnano.9b09282 pmid: 32017535
[21]	Huang, S.; Liu, H.; Liao, K.; Hu, Q.; Guo, R.; Deng, K. ACS Appl. Mater. Interfaces 2020, 12, 28952.
[22]	Wu, Q.; Peng, R.; Luo, Y.; Cui, Q.; Zhu, S.; Li, L. ACS Appl. Bio Mater. 2021, 4, 5071. doi: 10.1021/acsabm.1c00318
[23]	Hu, D.; Zou, L.; Li, B.; Hu, M.; Ye, W.; Ji, J. ACS Biomater. Sci. Eng. 2019, 5, 5169. doi: 10.1021/acsbiomaterials.9b01173
[24]	Mei, L.; Gao, X.; Shi, Y.; Cheng, C.; Shi, Z.; Jiao, M.; Cao, F.; Xu, Z.; Li, X. ACS Appl. Mater. Interfaces 2020, 12, 40153. doi: 10.1021/acsami.0c13237
[25]	Zhang, R.; Yu, J.; Ma, K.; Ma, Y.; Wang, Z. ACS Appl. Bio Mater. 2020, 3, 7168. doi: 10.1021/acsabm.0c00979
[26]	Zhou, K.; Qiu, X.; Xu, L.; Li, G.; Rao, B.; Guo, B.; Pei, D.; Li, A.; He, G. ACS Appl. Mater. Interfaces 2020, 12, 26432. doi: 10.1021/acsami.0c04506
[27]	Yu, H.; Liu, L.; Yang, H.; Zhou, R.; Che, C.; Li, X.; Li, C.; Luan, S.; Yin, J.; Shi, H. ACS Appl. Mater. Interfaces 2018, 10, 39257. doi: 10.1021/acsami.8b13868
[28]	Abri, S.; Ghatpande, A. A.; Ress, J.; Barton, H. A.; Leipzig, N. D. ACS Appl. Bio Mater. 2019, 2, 5848. doi: 10.1021/acsabm.9b00833
[29]	Zhi, Z.; Su, Y.; Xi, Y.; Tian, L.; Xu, M.; Wang, Q.; Padidan, S.; Li, P.; Huang, W. ACS Appl. Mater. Interfaces 2017, 9, 10383. doi: 10.1021/acsami.6b12979
[30]	Li, W.; Zhang, H.; Li, X.; Yu, H.; Che, C.; Luan, S.; Ren, Y.; Li, S.; Liu, P.; Yu, X.; Li, X. ACS Appl. Mater. Interfaces 2020, 12, 7617. doi: 10.1021/acsami.9b22206
[31]	Xu, M.; Zhou, H.; Liu, Y.; Sun, J.; Xie, W.; Zhao, P.; Liu, J. ACS Appl. Mater. Interfaces 2018, 10, 32965. doi: 10.1021/acsami.8b08230
[32]	Wang, S.; Li, C.; Meng, Y.; Qian, M.; Jiang, H.; Du, Y.; Huang, R.; Wang, Y. ACS Biomater. Sci. Eng. 2017, 3, 1702. doi: 10.1021/acsbiomaterials.7b00326
[33]	Cai, X.; Yan, H.; Luo, Y.; Song, Y.; Zhao, Y.; Li, H.; Du, D.; Lin, Y. ACS Appl. Bio Mater. 2018, 1, 1165. doi: 10.1021/acsabm.8b00381
[34]	Ng, I. S.; Ooi, C. W.; Liu, B. L.; Peng, C. T.; Chiu, C. Y.; Chang, Y. K. Int. J. Biol. Macromol. 2020, 154, 844. doi: S0141-8130(20)31339-8 pmid: 32194127
[35]	Yu, S.; Li, G.; Liu, R.; Ma, D.; Xue, W. Adv. Funct. Mater. 2018, 28, 1707440. doi: 10.1002/adfm.201707440
[36]	Peng, J.; Liu, P.; Peng, W.; Sun, J.; Dong, X.; Ma, Z.; Gan, D.; Liu, P.; Shen, J. J. Hazard. Mater. 2021, 411, 125110. doi: 10.1016/j.jhazmat.2021.125110
[37]	Jia, X.; Ahmad, I.; Yang, R.; Wang, C. J. Mater. Chem. B 2017, 5, 2459. doi: 10.1039/C6TB03084J
[38]	Liu, C.; Wei, Z.; Huo, Z.; Fu, S.; Li, S.; Yang, Y.; Shi, J.; Wu, Q. ACS Appl. Bio Mater. 2020, 3, 5048. doi: 10.1021/acsabm.0c00551
[39]	Sang, Y.; Li, W.; Liu, H.; Zhang, L.; Wang, H.; Liu, Z.; Ren, J.; Qu, X. Adv. Funct. Mater. 2019, 29, 1900518. doi: 10.1002/adfm.v29.22
[40]	Yin, W.; Yu, J.; Lv, F.; Yan, L.; Zheng, L.; Gu, Z. ACS Nano 2016, 10, 11000. doi: 10.1021/acsnano.6b05810

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