H2S Donor Functionalized Molecular Machine for Combating Multidrug-Resistant Bacteria Infected Chronic Wounds
Yuan Chen
School of Biomedical Engineering, Sichuan University, Chengdu, 610065 P.R. China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorKun-Mei Liu
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorLing-Xiao Zhou
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorJin-Yu An
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorCorresponding Author
Prof. Shun Feng
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Ming-Yu Wu
School of Biomedical Engineering, Sichuan University, Chengdu, 610065 P.R. China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Xiao-Qi Yu
School of Biomedical Engineering, Sichuan University, Chengdu, 610065 P.R. China
Asymmetric Synthesis and Chiral Technology, Key Laboratory of Sichuan Province, Department of Chemistry, Xihua University, Chengdu, 610039 P.R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorYuan Chen
School of Biomedical Engineering, Sichuan University, Chengdu, 610065 P.R. China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorKun-Mei Liu
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorLing-Xiao Zhou
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorJin-Yu An
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
Search for more papers by this authorCorresponding Author
Prof. Shun Feng
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Ming-Yu Wu
School of Biomedical Engineering, Sichuan University, Chengdu, 610065 P.R. China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 P.R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Xiao-Qi Yu
School of Biomedical Engineering, Sichuan University, Chengdu, 610065 P.R. China
Asymmetric Synthesis and Chiral Technology, Key Laboratory of Sichuan Province, Department of Chemistry, Xihua University, Chengdu, 610039 P.R. China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorGraphical Abstract
A novel H2S donor functionalized molecular machine, ACR-DM-HS, with combination of antibacteria and anti-inflammation to accelerate angiogenesis through membrane disruption, ROS generation, and H2S releasing was developed for synergistic therapy of multiple resistant bacteria-infected chronic wound, which offers a promising treatment approach for combating bacterial multidrug resistance and tackling chronic wounds.
Abstract
Chronic wounds are a worldwide medical challenge due to the complex and multifaceted etiologies, including bacterial infection, persistent inflammation, and impaired angiogenesis. Developing a comprehensive strategy integrating antibiosis and anti-inflammation to promote revascularization and accelerate wound healing is highly desirable. Nevertheless, current therapeutic methods still face two major challenges: 1) how to combat bacterial drug resistance, 2) how to achieve spatiotemporal control over bacterial elimination and inflammation reduction. To address these issues, a novel H2S donor functionalized molecular machine (MM), ACR-DM-HS, was developed. It selectively binds to and disturbs the bacterial membrane through a light-active vibronic-driven mechanochemical action (VDA), which synergizes with photodynamic therapy (PDT) to efficiently eradicate multidrug-resistant bacteria and biofilms, and conquers the evolution of bacterial resistance. Furthermore, it releases H2S in infected tissues to scavenge excess reactive oxygen species (ROS), inhibit the secretion of inflammatory factors, promote angiogenesis, and accelerate the healing of diabetic wounds in vivo. This work provides an integrated strategy combining antibiotics and anti-inflammation to treat with multidrug resistance bacterial-infected chronic wounds.
Conflict of Interests
The authors M.-Y.W., Y.C., and X.-Q.Y. declare that they have filed a Chinese patent application (2024108606672) based on the findings in this paper. Other authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
Filename | Description |
---|---|
anie202507833-sup-0001-SupMat.docx67.8 MB | Supporting Information |
anie202507833-sup-0002-SupMat.mp41 MB | Supporting Information |
anie202507833-sup-0003-SupMat.mp41 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1V. Falanga, R. R. Isseroff, A. M. Soulika, M. Romanelli, D. Margolis, S. Kapp, M. Granick, K. Harding, Nat. Rev. Dis. Primers 2022, 8, 50.
- 2R. M. Mizelle, Lancet 2021, 397, 1256–1257.
- 3C. Wang, E. Shirzaei Sani, C. D. Shih, C. T. Lim, J. Wang, D. G. Armstrong, W. Gao, Nat. Rev. Mater. 2024, 9, 550–566.
- 4A. Uberoi, A. McCready-Vangi, E. A. Grice, Nat. Rev. Microbiol. 2024, 22, 507–521.
- 5F. Zhao, Y. Su, J. Wang, S. Romanova, D. J. DiMaio, J. Xie, S. Zhao, Adv. Mater. 2023, 35, 2208069.
- 6K. Bae, W. Zheng, Y. Ma, Z. Huang, Theranostics 2019, 9, 1348–1357.
- 7D. G. Armstrong, T.-W. Tan, A. J. M. Boulton, S. A. Bus, JAMA 2023, 330, 62.
- 8M. Xue, R. Zhao, H. Lin, C. Jackson, Adv. Drug Delivery Rev. 2018, 129, 219–241.
- 9P. Ma, C. Y. Yang, C. Li, P. Hu, F. Yang, J. Lu, Y.-Y. Huang, H. Wu, Q. Wu, Y. Pan, X. Wang, Adv. Fiber Mater. 2024, 6, 543–560.
- 10Z. Hu, J. Shan, Y. Cui, L. Cheng, X. L. Chen, X. Wang, Adv. Healthcare Mater. 2024, 13, 2400101.
- 11B. Guo, R. Dong, Y. Liang, M. Li, Nat. Rev. Chem. 2021, 5, 773–791.
- 12X.-L. Lei, K. Cheng, Y. Li, Z.-T. Zhong, X.-L. Hou, L.-B. Song, F. Zhang, J.-H. Wang, Y.-D. Zhao, Q.-R. Xu, Chem. Eng. J. 2023, 462, 142222.
- 13H. Peng, D. Rossetto, S. S. Mansy, M. C. Jordan, K. P. Roos, I. A. Chen, ACS Nano 2022, 16, 4756–4774.
- 14C. Elian, R. Méallet, D. L. Versace, Adv. Funct. Mater. 2024, 34, 2407228.
- 15Y.-Y. Wang, J.-M. Xiong, L.-W. Xin, Y.-Y. Li, H. Huang, W.-J. Miao, Chinese Chem. Lett. 2025, 36, 110003.
- 16J. Xi, G. Wei, L. An, Z. Xu, Z. Xu, L. Fan, L. Gao, Nano Lett. 2019, 19, 7645–7654.
- 17X. Luo, L. Zhang, Y. Luo, Z. Cai, H. Zeng, T. Wang, Z. Liu, Y. Chen, X. Sheng, A. E. D. G. Mandlate, Z. Zhou, F. Chen, L. Zheng, Adv. Funct. Mater. 2023, 33, 2214036.
- 18L. Huelsboemer, L. Knoedler, A. Kochen, C. T. Yu, H. Hosseini, K. S. Hollmann, A. E. Choi, V. A. Stögner, S. Knoedler, H. C. Hsia, B. Pomahac, M. Kauke-Navarro, Mil. Med. Res. 2024, 11, 23.
- 19M. Kharaziha, A. Baidya, N. Annabi, Adv. Mater. 2021, 33, 2100176.
- 20X. Zhou, P. Zhang, H. Ding, H. Wang, Z. Gu, Nano Today 2024, 56, 102225.
- 21A. Panáček, L. Kvítek, M. Smékalová, R. Večeřová, M. Kolář, M. Röderová, F. Dyčka, M. Šebela, R. Prucek, O. Tomanec, R. Zbořil, Nat. Nanotechnol. 2018, 13, 65–71.
- 22X. Zhao, D. Pei, Y. Yang, K. Xu, J. Yu, Y. Zhang, Q. Zhang, G. He, Y. Zhang, A. Li, Y. Cheng, X. Chen, Adv. Funct. Mater. 2021, 31, 2009442.
- 23J. Yang, W. Zeng, P. Xu, X. Fu, X. Yu, L. Chen, F. Leng, C. Yu, Z. Yang, Acta Biomater. 2022, 140, 206–218.
- 24C. Ayala-Orozco, G. Li, B. Li, V. Vardanyan, A. B. Kolomeisky, J. M. Tour, Adv. Mater. 2024, 36, 2309910.
- 25C. Ayala-Orozco, D. Galvez-Aranda, A. Corona, J. M. Seminario, R. Rangel, J. N. Myers, J. M. Tour, Nat. Chem. 2024, 16, 456–465.
- 26M. Guentner, M. Schildhauer, S. Thumser, P. Mayer, D. Stephenson, P. J. Mayer, H. Dube, Nat. Commun. 2015, 6, 8406.
- 27A. L. Santos, D. Liu, A. K. Reed, A. M. Wyderka, A. van Venrooy, J. T. Li, V. D. Li, M. Misiura, O. Samoylova, J. L. Beckham, C. Ayala-Orozco, A. B. Kolomeisky, L. B. Alemany, A. Oliver, G. P. Tegos, J. M. Tour, Sci. Adv. 2022, 8, eabm2055.
- 28V. García-López, F. Chen, L. G. Nilewski, G. Duret, A. Aliyan, A. B. Kolomeisky, J. T. Robinson, G. Wang, R. Pal, J. M. Tour, Nature 2017, 548, 567–572.
- 29Y. Sun, X. Sun, X. Li, W. Li, C. Li, Y. Zhou, L. Wang, B. Dong, Biomaterials 2021, 268, 120614.
- 30R. Xu, Y. Fan, J. Gu, W. Cao, R. Deng, Z. Rana, X. Lu, C. Xu, G. Xiang, H. Li, X. Wang, Adv. Funct. Mater. 2024, 34, 2401307.
- 31X. Fang, J. Wang, C. Ye, J. Lin, J. Ran, Z. Jia, J. Gong, Y. Zhang, J. Xiang, X. Lu, C. Xie, J. Liu, Nat. Commun. 2024, 15, 9071.
- 32H. Ding, J. Chang, F. He, S. Gai, P. Yang, Adv. Healthcare Mater. 2022, 11, 2101984.
- 33M. He, Z. Wang, D. Xiang, D. Sun, Y. K. Chan, H. Ren, Z. Lin, G. Yin, Y. Deng, W. Yang, Adv. Mater. 2024, 36, 2405659.
- 34Y. Chen, R. Zhao, C. Tang, C. Zhang, W. Xu, L. Wu, Y. Wang, D. Ye, Y. Liang, Angew. Chem. Int. Ed. 2022, 61, e202112734.
- 35P. Shan, J. Liao, J. Li, C. Wang, J. Zhou, L. Mei, Y. Dai, Q. Wang, W. Yin, Chinese Chem. Lett. 2024, 35, 108545.
- 36J. Tian, B. Huang, L. Xia, Y. Zhu, W. Zhang, Adv. Sci. 2024, 11, 2305183.
- 37J. Chen, Z. Mu, D. Chen, C. Huang, T. Jin, L. Li, Y. Zeng, Q. Zhou, Y. Zhang, H. Mao, H. Deng, X. Shen, H. Yang, X. Cai, Chem. Eng. J. 2023, 469, 143985.
- 38Y. Huang, Y. Huang, Z. Wang, S. Yu, H. M. Johnson, Y. Yang, M. Li, J. Li, Y. Deng, K. Liang, Small 2023, 19, 2304324.
- 39A. Domán, É. Dóka, D. Garai, V. Bogdándi, G. Balla, J. Balla, P. Nagy, Redox Biol. 2023, 60, 102617.
- 40E. Glukhov, M. Stark, L. L. Burrows, C. M. Deber, J. Biol. Chem. 2005, 280, 33960–33967.
- 41M. P. Hughes, Integ. Biol 2024, 16, zyae003.
- 42J. Li, J. Li, J. He, X. He, D. Chen, Z. Dong, L. Xiong, W. Bai, M. Li, R. Guo, Q. He, Nano Res. 2024, 17, 9932–9941.
- 43Y. Zhang, M. Luo, X. Shi, A. Li, W. Zhou, Y. Yin, H. Wang, W.-L. Wong, X. Feng, Q. He, Sci. Adv. 2024, 10, eadp4872.
- 44H. Bai, H. Yuan, C. Nie, B. Wang, F. Lv, L. Liu, S. Wang, Angew. Chem. Int. Ed. 2015, 54, 13208–13213.
- 45J. L. Wang, X. Pan, X. Li, K. M. Liu, M. Yao, J. Y. An, Y. Wan, X. Q. Yu, S. Feng, M.-Y. Wu, Adv. Mater. 2024, 6, 2411468.
- 46L. Chen, M.-Y. Wu, S.-L. Chen, R. Hu, Y. Wang, W. Zeng, S. Feng, M. Ke, L. Wang, S. Chen, M. Gu, Adv. Mater. 2024, 36, 2407268.
- 47J. L. Wang, F.-W. Xia, Y. Wang, H. Z. Shi, L. J. Wang, Y. Zhao, J. X. Song, M.-Y. Wu, S. Feng, ACS Appl. Mater. Interfaces 2023, 15, 17433–17443.
- 48M.-Y. Wu, A. Y. H. Wong, J.-K. Leung, C. Kam, K. L.-K. Wu, Y.-S. Chan, K. Liu, N. Y. Ip, S. Chen, Proc. Natl. Acad. Sci. USA 2021, 118, e2106143118.
- 49M.-Y. Wu, Z.-J. Wu, J.-L. Wang, C. Kam, T. Y. Chou, S. Feng, K. Li, S. Chen, ACS Mater. Lett. 2024, 6, 4533–4544.
- 50M.-Y. Wu, J.-K. Leung, L. Liu, C. Kam, K. Y. K. Chan, R. A. Li, S. Feng, S. Chen, Angew. Chem. Int. Ed. 2020, 59, 10327–10331.
- 51F. W. Xia, B. W. Guo, Y. Zhao, J. L. Wang, Y. Chen, X. Pan, X. Li, J. X. Song, Y. Wan, S. Feng, M.-Y. Wu, Adv. Mater. 2023, 35, 2309797.
- 52A. Lauchner, A. E. Schlather, A. Manjavacas, Y. Cui, M. J. McClain, G. J. Stec, F. J. García de Abajo, P. Nordlander, N. J. Halas, Nano Lett. 2015, 15, 6208–6214.
- 53Y. Cui, A. Lauchner, A. Manjavacas, F. J. Garcı́a de Abajo, N. J. Halas, P. Nordlander, Nano Lett. 2016, 16, 6390–6395.
- 54T. Shigematsu, K. Koshiyama, S. Wada, Sci. Rep. 2015, 5, 15369.
- 55F. Li, C. U. Chan, C. D. Ohl, Biophys. J. 2013, 105, 872–879.
- 56B. Li, D. Wang, M. M. S. Lee, W. Wang, Q. Tan, Z. Zhao, B. Z. Tang, X. Huang, ACS Nano 2021, 15, 1385.
- 57S. K. Chung, J. Jung, Photochem. Photobiol. 1995, 61, 383–389.
- 58B. B. Fischer, A. Krieger-Liszkay, R. I. L. Eggen, Environ. Sci. Technol. 2004, 38, 6307–6313.
- 59Z. Liu, Q. Wang, W. Qiu, Y. Lyu, Z. Zhu, X. Zhao, W. H. Zhu, Chem. Sci. 2022, 13, 3599–3608.
- 60J. Liang, X. Ran, Y. Liu, X. Yu, S. Chen, K. Li, J. Mater. Chem. B 2024, 12, 3686–3693.
- 61X. Shi, S. H. P. Sung, J. H. C. Chau, Y. Li, Z. Liu, R. T. K. Kwok, J. Liu, P. Xiao, J. Zhang, B. Liu, J. W. Y. Lam, B. Z. Tang, Small Methods 2020, 4, 2000046.
- 62M.-Y. Wu, L. J. Wang, C.-M. Qin, Y. Wang, J. X. Song, Y. Zhao, Y. Wan, S. Feng, Sens. Actuators, B 2023, 381, 133471.
- 63Z. Gao, X. Zheng, W. Liu, J. Sha, S. Bian, H. Ren, J. Wu, W. Zhang, C.-S. Lee, P. Wang, Chinese Chem. Lett. 2025, 36, 109874.
- 64J. Zhuang, Z. Ma, N. Li, H. Chen, L. Yang, Y. Lu, K. Guo, N. Zhao, B. Z. Tang, Adv. Mater. 2024, 36, 2309488.
- 65X. Gong, Y. Han, T. Wang, G. Song, H. Chen, H. Tang, X. Huang, K. Deng, S. Wang, Y. Wang, Adv. Mater. 2025, 37, 2414357.
- 66J. L. Wang, Y. Chen, J. X. Song, B.-W. Guo, F.-W. Xia, Y. Wan, W. X. Wu, C. Zhang, S. Feng, M.-Y. Wu, Adv. Funct. Mater. 2024, 34, 2312162.
- 67H. Y. Heo, G. Zou, S. Baek, J. S. Kim, E. Mylonakis, F. M. Ausubel, H. Gao, W. Kim, Adv. Sci. 2024, 11, 2306112.
- 68J. Yang, Z. Zhai, J. Liu, C. Weng, J. Appl. Polym. Sci. 2021, 138, 50105.
- 69A. U. Mahmood, Y. G. Yingling, J. Chem. Theory Comput. 2022, 18, 3122–3135.
- 70M. Wu, C. Chen, Z. Liu, J. Tian, W. Zhang, Acta Biomater. 2022, 142, 242–252.
- 71M. Yang, Z. Özdemir, H. Kim, S. Nah, E. Andris, X. Li, Z. Wimmer, J. Yoon, Adv. Healthcare Mater. 2022, 11, 2200529.
- 72J. Jia, Z. Wang, M. Zhang, C. Huang, Y. Song, F. Xu, J. Zhang, J. Li, M. He, Y. Li, G. Ao, C. Hong, Y. Cao, Y. E. Chin, Z.-c. Hua, J. Cheng, Sci. Adv. 2020, 6, eaaz5752.
- 73M. Lee, V. Tazzari, D. Giustarini, R. Rossi, A. Sparatore, P. Del Soldato, E. McGeer, P. L. McGeer, J. Biol. Chem. 2010, 285, 17318–17328.
- 74J. Cheng, Y. Zhu, Y.i Dai, L.i Li, M. Zhang, D. Jin, M. Liu, J. Yu, W. Yu, D. Su, J. Zou, X. Chen, Y. Liu, Angew. Chem. Int. Ed. 2023, 62, e202304312.
- 75X. Zheng, H. Li, S. Gao, K. Müllen, J. Zhang, C. Ji, M. Yin, Small 2024, 20, 2403284.
- 76K. Cheng, B.o Liu, X.-S. Zhang, R.-Y. Zhang, F. Zhang, G. Ashraf, G.-Q. Fan, M.-Y.u Tian, X. Sun, J. Yuan, Y.-D.i Zhao, Nat. Commun. 2022, 13, 4567.
- 77Q. Ou, X. Qiao, Z. Li, L. Niu, F. Lei, R. Cheng, T. Xie, N. Yang, Y. Liu, L. Fu, J. Yang, X. Mao, X. Kou, C. Chen, S. Shi, Cell Metab. 2024, 36, 78–89.
- 78L. B. Case, M. A. Baird, G. Shtengel, S. L. Campbell, H. F. Hess, M. W. Davidson, C. M. Waterman, Nat. Cell Biol. 2015, 17, 880–892.
- 79T. Wei, T. Pan, X. Peng, M. Zhang, R. Guo, Y. Guo, X. Mei, Y. Zhang, J. Qi, F. Dong, M. Han, F. Kong, L. Zou, D. Li, D. Zhi, W. Wu, D. Kong, S. Zhang, C. Zhang, Nat. Nanotechnol. 2024, 19, 1178–1189.
- 80Y. Kang, L. Xu, J. Dong, X. Yuan, J. Ye, Y. Fan, B. Liu, J. Xie, X. Ji, Nat. Commun. 2024, 15, 1042.
- 81Y. Gao, Y. Deng, W. Geng, S. Xiao, T. Wang, X. Xu, M. Adeli, L. Cheng, L. Qiu, C. Cheng, Adv. Mater. 2024, 36, 2408787.
- 82Y. Cai, K. Chen, C. Liu, X. Qu, Bioact. Mater. 2023, 28, 243.
- 83C. Oh, W. Lee, J. Park, J. Choi, S. Lee, S. Li, H. N. Jung, J.-S. Lee, J.-E. Hwang, J. Park, M. Kim, S. Baek, H.-J. Im, ACS Nano 2023, 17, 4327–4345.
- 84R. S. Apte, D. S. Chen, N. Ferrara, Cell 2019, 176, 1248–1264.
- 85M.-Y. Wu, X. Xu, R. Hu, Q. Chen, L. Chen, Y. Yuan, J. Li, L.i Zhou, S. Feng, L. Wang, S. Chen, M. Gu, Adv. Sci. 2023, 10, 2207736.
- 86J. Wang, X. Ge, Y. Xiang, X. Qi, Y. Li, H. Xu, E. Cai, C. Zhang, Y. Lan, X. Chen, Y. Shi, Z. Li, J. Shen, Chinese Chem. Lett. 2025, 36, 109819.
- 87J. Massagué, D. Sheppard, Cell 2023, 186, 4007–4037.