A self-regulated phototheranostic nanosystem with single wavelength-triggered energy switching and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections

Abstract

The exploration of antibiotic-independent phototherapy strategies for the treatment of bacterial biofilm infections has gained significant attention. However, efficient eradication of bacterial biofilms remains a challenge. Herein, a self-regulated phototheranostic nanosystem with single wavelength-triggered photothermal therapy (PTT)/photodynamic therapy (PDT) transformation and oxygen supply for multimodal synergistic therapy of bacterial biofilm infections is presented. This approach combines a eutectic mixture of natural phase-change materials (PCMs) and an aggregation-induced emission (AIE) phototheranostic agent TPA-ICN to form colloidally stable nanopartcicles (i.e. AIE@PCM NPs). The reversible solid–liquid phase transition of PCMs facilitates the adaptive regulation of the aggregation states of TPA-ICN, enabling a switch between the energy dissipation pathways for enhanced PDT in solid PCMs or enhanced PTT in liquid PCMs. Additionally, oxygen-carrying thermoresponsive nanoparticles are also introduced to alleviate the hypoxic microenvironment of biofilms by releasing oxygen upon heating by AIE@PCM NPs with enhanced PTT. The nanosystem exhibits outstanding therapeutic efficacy against bacterial biofilms both in vitro and in vivo, with an antibacterial efficiency of 99.99%. This study utilizes a self-regulated theranostic nanoplatform with adaptive PTT/PDT transformation via the phase transition of PCMs and heattriggered oxygen release, holding great promise in the safe and efficient treatment of bacterial biofilm infections.

Keywords

bacterial biofilm infections / hypoxic microenvironments / multimodal synergistic therapy / phase-change materials / phototheranostic agents

References

[1] C. Nathan, Nat. Rev. Microbiol. 2020, 18, 259.

[2] J. A. Jernigan, K. M. Hatfield, H. Wolford, R. E. Nelson, B. Olubajo, S. C. Reddy, N. McCarthy, P. Paul, L. C. McDonald, A. Kallen, A. Fiore, M. Craig, J. Baggs, N. Engl. J. Med. 2020, 382, 1309.

[3] J. M. V Makabenta, A. Nabawy, C.-H. Li, S. Schmidt-Malan, R. Patel, V. M. Rotello, Nat. Rev. Microbiol. 2021, 19, 23.

[4] J. W. Costerton, P. S. Stewart, E. P. Greenberg, Science 1999, 284, 1318.

[5] Y. Chen, Y. Gao, Y. Huang, Q. Jin, J. Ji, ACS Nano 2023, 17, 10019.

[6] H.-C. Flemming, J. Wingender, U. Szewzyk, P. Steinberg, S. A. Rice, S. Kjelleberg, Nat. Rev. Microbiol. 2016, 14, 563.

[7] H. Koo, R. N. Allan, R. P. Howlin, P. Stoodley, L. Hall-Stoodley, Nat. Rev. Microbiol. 2017, 15, 740.

[8] D. Fan, X. Liu, Y. Ren, Z. Luo, Y. Li, J. Dong, S. V. Wegner, F. Chen, W. Zeng, Acta Pharm. Sin. B 2024, 14, 1759.

[9] J. Qi, H. Ou, Q. Liu, D. Ding, Aggregate 2021, 2, 95.

[10] R. Qu, X. Zhen, X. Jiang, CCS Chem. 2022, 4, 401.

[11] Y.-Y. Zhao, H. Kim, V.-N. Nguyen, S. Jang, W. J. Jang, J. Yoon, Coord. Chem. Rev. 2024, 501, 215560.

[12] T. C. Pham, V.-N. Nguyen, Y. Choi, S. Lee, J. Yoon, Chem. Rev. 2021, 121, 13454.

[13] X. Liu, M. Xiao, K. Xue, M. Li, D. Liu, Y. Wang, X. Yang, Y. Hu, R. T. K. Kwok, A. Qin, C. Zhu, J. W. Y. Lam, B. Z. Tang, Angew. Chem. Int. Ed. 2021, 60, 19222.

[14] F. Wang, Y. Shi, P.-Y. Ho, E. Zhao, C. Kam, Q. Zhang, X. Zhao, Y. Pan, S. Chen, Bioeng. Transl. Med. 2023, 8, e10539.

[15] S. Wang, W.-Y. Wu, J. C. C. Yeo, X. Y. D. Soo, W. Thitsartarn, S. Liu, B. H. Tan, A. Suwardi, Z. Li, Q. Zhu, X. J. Loh, BMEMat. 2023, 1, e12021.

[16] J. Huo, Q. Jia, H. Huang, J. Zhang, P. Li, X. Dong, W. Huang, Chem. Soc. Rev. 2021, 50, 8762.

[17] K. Xue, C. Yang, C. Wang, Y. Liu, J. Liu, L. Shi, C. Zhu, CCS Chem. 2022, 4, 272.

[18] J. Wang, B. Hao, K. Xue, H. Fu, M. Xiao, Y. Zhang, L. Shi, C. Zhu, Adv. Mater. 2022, 34, 2205653.

[19] W. Shao, F. Zhao, J. Xue, L. Huang, BMEMat. 2023, 1, e12009.

[20] Z. Zhang, W. Xu, M. Kang, H. Wen, H. Guo, P. Zhang, L. Xi, K. Li, L. Wang, D. Wang, B. Z. Tang, Adv. Mater. 2020, 32, 2003210.

[21] Z. Yuan, J. Wu, Y. Xiao, H. Yang, S. Meng, L. Dai, P. Li, K. Cai, Adv. Funct. Mater. 2023, 33, 2302908.

[22] C. Yang, M. Su, P. Luo, Y. Liu, F. Yang, C. Li, Small 2021, 17, 2101180.

[23] B. Zhang, H. Yan, Z. Meng, P. Li, X. Jiang, Z. Wu, J.-A. Xiao, W. Su, ACS Appl. Bio Mater. 2021, 4, 6742.

[24] S. Zhang, Z. Li, Q. Wang, Q. Liu, W. Yuan, W. Feng, F. Li, Adv. Mater. 2022, 34, 2201978.

[25] D. Yan, Y. Huang, J. Zhang, Q. Wu, G. Song, J. Ji, Q. Jin, D. Wang, B. Z. Tang, J. Am. Chem. Soc. 2023, 145, 25705.

[26] C. Zhu, R. T. K. Kwok, J. W. Y. Lam, B. Z. Tang, ACS Appl. Bio Mater. 2018, 1, 1768.

[27] P.-Y. Ho, S.-Y. Lee, C. Kam, J. Zhu, G.-G. Shan, Y. Hong, W.-Y. Wong, S. Chen, Adv. Healthcare Mater. 2021, 10, 2100706.

[28] M. Xiao, K. Xue, H. Fu, J. Wang, S. Lv, Z. Sun, C. Wang, C. Zhu, Aggregate 2024, e532.

[29] X. Liu, C. Zhu, B. Z. Tang, Acc. Chem. Res. 2022, 55, 197.

[30] S. Lv, C. Wang, K. Xue, J. Wang, M. Xiao, Z. Sun, L. Han, L. Shi, C. Zhu, Proc. Natl. Acad. Sci. U. S. A. 2023, 120, e2302367120.

[31] Y. Wan, L.-H. Fu, C. Li, J. Lin, P. Huang, Adv. Mater. 2021, 33, 2103978.

[32] X. Song, L. Feng, C. Liang, K. Yang, Z. Liu, Nano Lett. 2016, 16, 6145.

[33] Z. Yuan, S. Yu, F. Cao, Z. Mao, C. Gao, J. Ling, Polym. Chem. 2018, 9, 2124.

[34] W. Tang, Z. Zhen, M. Wang, H. Wang, Y.-J. Chuang, W. Zhang, G. D. Wang, T. Todd, T. Cowger, H. Chen, L. Liu, Z. Li, J. Xie, Adv. Funct. Mater. 2016, 26, 1757.

[35] J.-M. Aubry, C. Pierlot, J. Rigaudy, R. Schmidt, Acc. Chem. Res. 2003, 36, 668.

[36] W. Fudickar, T. Linker, J. Am. Chem. Soc. 2012, 134, 15071.

[37] S. Kolemen, T. Ozdemir, D. Lee, G. M. Kim, T. Karatas, J. Yoon, E. U. Akkaya, Angew. Chem. Int. Ed. 2016, 55, 3606.

[38] C. Zhu, D. Huo, Q. Chen, J. Xue, S. Shen, Y. Xia, Adv. Mater. 2017, 29, 1703702.

[39] J. Qiu, D. Huo, J. Xue, G. Zhu, H. Liu, Y. Xia, Angew. Chem. Int. Ed. 2019, 58, 10606.

[40] K. Xue, C. Wang, J. Wang, S. Lv, B. Hao, C. Zhu, B. Z. Tang, J. Am. Chem. Soc. 2021, 143, 14147.

[41] B. Mai, M. Jia, S. Liu, Z. Sheng, M. Li, Y. Gao, X. Wang, Q. Liu, P. Wang, ACS Appl. Mater. Interfaces 2020, 12, 10156.

[42] Z. Wang, P. Zhang, C. Yin, Y. Li, Z. Liao, C. Yang, H. Liu, W. Wang, C. Fan, D. Sun, L. Cheng, Adv. Funct. Mater. 2023, 33, 2300341.

[43] L. Jin, F. Cao, Y. Gao, C. Zhang, Z. Qian, J. Zhang, Z. Mao, Adv. Mater. 2023, 35, 2301349.

[44] Z. Liu, K. Guo, L. Yan, K. Zhang, Y. Wang, X. Ding, N. Zhao, F.-J. Xu, Nat. Commun. 2023, 14, 5132.

[45] J. Yi, S. Xiao, M. Yin, M. Su, C. Gao, R. Tang, Adv. Funct. Mater. 2023, 33, 2302322.

[46] A. F. McGettrick, L. A. J. O’Neill, Cell Metab. 2020, 32, 524.

[47] H. Zhao, J. Huang, Y. Li, X. Lv, H. Zhou, H. Wang, Y. Xu, C. Wang, J. Wang, Z. Liu, Biomaterials 2020, 258, 120286.

[48] J.-J. Li, Y. Hu, B. Hu, W. Wang, H. Xu, X.-Y. Hu, F. Ding, H.-B. Li, K.-R. Wang, X. Zhang, D.-S. Guo, Nat. Commun. 2022, 13, 6279.

[49] H. Fu, K. Xue, Y. Zhang, M. Xiao, K. Wu, L. Shi, C. Zhu, Adv. Sci. 2023, 10, 2206865.

[50] K. Xue, S. Lv, C. Zhu, J. Mater. Chem. B 2021, 9, 6973.

[51] C. Zhu, P. Pradhan, D. Huo, J. Xue, S. Shen, K. Roy, Y. Xia, Angew. Chem. Int. Ed. 2017, 56, 10399.

[52] D. G. Mashek, R. A. Coleman, Curr. Opin. Lipidol. 2006, 17, 274.

[53] E. Currie, A. Schulze, R. Zechner, T. C. Walther, R. V. Farese, Cell Metab. 2013, 18, 153.

[54] A. Carracedo, L. C. Cantley, P. P. Pandolfi, Nat. Rev. Cancer 2013, 13, 227

RIGHTS & PERMISSIONS

2024 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.