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RESEARCH ARTICLE
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Living hybrid material based on probiotic with photothermal properties inhibits PD-L1 expression after tumouricidal photothermal therapy

Ning Jiang1 Mingyan Jiang2 Jianshu Chen1 Ali Mohsin1 Yuqing Mu3 Xiaoping Yi1 Yingping Zhuang1 Jiangchao Qian1 Jiaofang Huang1,2*
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1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China
2 College of Life Sciences, Jiangxi Normal University, Nanchang, Jiangxi Province, China
3 Institute for biomedicine and glycomics, Griffith University School of Medicine and Dentistry, Griffith University, Queensland, Australia
Submitted: 30 October 2024 | Revised: 22 November 2024 | Accepted: 25 February 2025 | Published: 25 March 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
Abstract

Photothermal therapy is a safe and effective tumour treatment strategy due to its excellent spatiotemporal controllability. However, interferon gamma in the tumour microenvironment is upregulated after photothermal therapy, which enhances the expression of programmed cell death ligand 1 (PD-L1) in tumour cells. This further promotes immunosuppression and tumour metastasis, resulting in a poor prognosis in cancer therapy. Traditional nanodrugs often face challenges in penetrating the dense extracellular matrix of solid tumours, whereas certain probiotics possess the ability to specifically colonise the core regions of tumours. In this research, we used Escherichia coli Nissle 1917 (ECN) as a chassis cell and self-assembly polydopamine (PDA) on the ECN surface. The black PDA@ECN (notes as PE) actively colonises at the tumour site and produces a photothermal effect under 808 nm laser irradiation to kill tumour cells. To overcome the high expression of PD-L1 induced after photothermal therapy, metformin (MET) was also encapsulated in PE to form PDA@MET@ECN (notes as PME). In vivo experiments demonstrated that PME effectively inhibited the PD-L1 expression and growth of CT26 tumour cells. Overall, PME reverses the immunosuppressive tumour microenvironment and enhances the effect of photothermal/immune therapy in tumour treatment.

Keywords
biomaterials
Escherichia coli Nissle 1917
programmed cell death ligand 1
photothermal therapy
Funding
This study was supported by the National Key Research and Development Program of China (No. 2020YFA0908900), the Natural Science Foundation of Shanghai (No. 22ZR1416000), and the Open Funding Project of State Key Laboratory of Microbial Metabolism (No. MMLKF24-01).
References

Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.

  1. Li, X.; Yong, T.; Wei, Z.; Bie, N.; Zhang, X.; Zhan, G.; Li, J.; Qin, J.; Yu, J.; Zhang, B.; Gan, L.; Yang, X. Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts. Nat Commun. 2022, 13, 2794.

 

  1. Ji, B.; Wei, M.; Yang, B. Recent advances in nanomedicines for photodynamic therapy (PDT)-driven cancer immunotherapy. 2022, 12, 434-458.

 

  1. Overchuk, M.; Weersink, R. A.; Wilson, B. C.; Zheng, G. Photodynamic and photothermal therapies: synergy opportunities for nanomedicine. ACS Nano. 2023, 17, 7979-8003.

 

  1. Jiang, N.; Zhou, Z.; Xiong, W.; Chen, J.; Shen, J.; Li, R.; Ye, R. Tumor microenvironment triggered local oxygen generation and photosensitizer release from manganese dioxide mineralized albumin- ICG nanocomplex to amplify photodynamic immunotherapy efficacy. Chin Chem Lett. 2021, 32, 3948-3953.

 

  1. Peng, D.; Fu, M.; Wang, M.; Wei, Y.; Wei, X. Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol Cancer. 2022, 21, 104.

 

  1. Bagrov, D. V.; Adlerberg, V. V.; Skryabin, G. O.; Nikishin, II; Galetsky, S. A.; Tchevkina, E. M.; Kirpichnikov, M. P.; Shaitan, K. V. AFM-TEM correlation microscopy and its application to lipid nanoparticles. Microsc Res Tech. 2023, 86, 781-790.

 

  1. Dong, X.; Zang, C.; Sun, Y.; Zhang, S.; Liu, C.; Qian, J. Hydroxyapatite nanoparticles induced calcium overload-initiated cancer cell-specific apoptosis through inhibition of PMCA and activation of calpain. J Mater Chem B. 2023, 11, 7609-7622.

 

  1. Liu, K.; Cheng, M.; Huang, H.; Yu, H.; Zhao, S.; Zhou, J.; Tie, D.; Wang, J.; Pan, P.; Chen, J. Abalone shell-derived Mg-doped mesoporous hydroxyapatite microsphere drug delivery system loaded with icariin for inducing apoptosis of osteosarcoma cells. Biomater Transl. 2024, 5, 185-196.

 

  1. Xi, Y.; Chen, L.; Tang, J.; Yu, B.; Shen, W.; Niu, X. Amplifying “eat me signal” by immunogenic cell death for potentiating cancer immunotherapy. Immunol Rev. 2024, 321, 94-114.

 

  1. Xiong, W.; Qi, L.; Jiang, N.; Zhao, Q.; Chen, L.; Jiang, X.; Li, Y.; Zhou, Z.; Shen, J. Metformin liposome-mediated PD-L1 downregulation for amplifying the photodynamic immunotherapy efficacy. ACS Appl Mater Interfaces. 2021, 13, 8026-8041.

 

  1. Kim, Y.; Vagia, E.; Viveiros, P.; Kang, C. Y.; Lee, J. Y.; Gim, G.; Cho, S.; Choi, H.; Kim, L.; Park, I.; Choi, J.; Chae, Y. K. Overcoming acquired resistance to PD-1 inhibitor with the addition of metformin in small cell lung cancer (SCLC). Cancer Immunol Immunother. 2021, 70, 961-965.

 

  1. Hughes, T.; Klairmont, M.; Sharfman, W. H.; Kaufman, H. L. Interleukin-2, Ipilimumab, and anti-PD-1: clinical management and the evolving role of immunotherapy for the treatment of patients with metastatic melanoma. Cancer Biol Ther. 2021, 22, 513-526.

 

  1. Yin, S.; Chen, Z.; Chen, D.; Yan, D. Strategies targeting PD-L1 expression and associated opportunities for cancer combination therapy. Theranostics. 2023, 13, 1520-1544.

 

  1. Han, Y.; Wang, L.; Cao, K.; Zhou, J.; Zhu, Y.; Hou, Y.; Lu, Y. In Situ TEM Characterization and modulation for phase engineering of nanomaterials. Chem Rev. 2023, 123, 14119-14184.

 

  1. Kong, N.; Ma, H.; Pu, Z.; Wan, F.; Li, D.; Huang, L.; Lian, J.; Huang, X.; Ling, S.; Yu, H.; Yao, Y. De novo design and synthesis of polypeptide immunomodulators for resetting macrophage polarization. Biodes Res. 2023, 5, 0006.

 

  1. Huang, X.; Pan, J.; Xu, F.; Shao, B.; Wang, Y.; Guo, X.; Zhou, S. Bacteria-based cancer immunotherapy. Adv Sci (Weinh). 2021, 8, 2003572.

 

  1. Lin, D.; Feng, X.; Mai, B.; Li, X.; Wang, F.; Liu, J.; Liu, X.; Zhang, K.; Wang, X. Bacterial-based cancer therapy: an emerging toolbox for targeted drug/gene delivery. Biomaterials. 2021, 277, 121124.

 

  1. Dong, X.; Wu, W.; Pan, P.; Zhang, X. Z. Engineered living materials for advanced diseases therapy. Adv Mater. 2023, e2304963.

 

  1. Li, J.; Xia, Q.; Guo, H.; Fu, Z.; Liu, Y.; Lin, S.; Liu, J. Decorating bacteria with triple immune nanoactivators generates tumor-resident living immunotherapeutics. Angew Chem Int Ed Engl. 2022, 61, e202202409.

 

  1. Luo, H.; Wu, F.; Wang, X.; Lin, S.; Zhang, M.; Cao, Z.; Liu, J. Encoding bacterial colonization and therapeutic modality by wrapping with an adhesive drug-loadable nanocoating. Mater Today. 2023, 62, 98-110.

 

  1. Liu, Y.; Zhang, M.; Wang, X.; Yang, F.; Cao, Z.; Wang, L.; Liu, J. Dressing bacteria with a hybrid immunoactive nanosurface to elicit dual anticancer and antiviral immunity. Adv Mater. 2023, 35, e2210949.

 

  1. Sun, R.; Liu, M.; Lu, J.; Chu, B.; Yang, Y.; Song, B.; Wang, H.; He, Y. Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy. Nat Commun. 2022, 13, 5127.

 

  1. Wang, Y.; Zhou, S. K.; Wang, Y.; Lu, Z. D.; Zhang, Y.; Xu, C. F.; Wang, J. Engineering tumor-specific gene nanomedicine to recruit and activate T cells for enhanced immunotherapy. Nat Commun. 2023, 14, 1993.

 

  1. Peng, R.; Ba, F.; Li, J.; Cao, J.; Zhang, R.; Liu, W. Q.; Ren, J.; Liu, Y.; Li, J.; Ling, S. Embedding living cells with a mechanically reinforced and functionally programmable hydrogel fiber platform. Adv Mater. 2023, 35, e2305583.

 

  1. Zhao, R.; Li, Z.; Sun, Y.; Ge, W.; Wang, M.; Liu, H.; Xun, L.; Xia, Y. Engineered Escherichia coli Nissle 1917 with urate oxidase and an oxygen-recycling system for hyperuricemia treatment. Gut Microbes. 2022, 14, 2070391.

 

  1. Chen, W.; Wang, Y.; Qin, M.; Zhang, X.; Zhang, Z.; Sun, X.; Gu, Z. Bacteria-driven hypoxia targeting for combined biotherapy and photothermal therapy. ACS Nano. 2018, 12, 5995-6005.

 

  1. Li, J.; Hou, W.; Lin, S.; Wang, L.; Pan, C.; Wu, F.; Liu, J. Polydopamine nanoparticle-mediated dopaminergic immunoregulation in colitis. Adv Sci (Weinh). 2022, 9, e2104006.

 

  1. Wang, X.; Lin, S.; Wang, L.; Cao, Z.; Zhang, M.; Zhang, Y.; Liu, R.; Liu, J. Versatility of bacterial outer membrane vesicles in regulating intestinal homeostasis. Sci Adv. 2023, 9, eade5079.

 

  1. Lin, S.; Wu, F.; Zhang, Y.; Chen, H.; Guo, H.; Chen, Y.; Liu, J. Surface-modified bacteria: synthesis, functionalization and biomedical applications. Chem Soc Rev. 2023, 52, 6617-6643.

 

  1. Yang, J. K.; Kwon, H.; Kim, S. Recent advances in light-triggered cancer immunotherapy. J Mater Chem B. 2024, 12, 2650-2669.

 

  1. Lou, X.; Chen, Z.; He, Z.; Sun, M.; Sun, J. Bacteria-mediated synergistic cancer therapy: small microbiome has a big hope. Nanomicro Lett. 2021, 13, 37.

 

  1. Chen, H.; Lei, P.; Ji, H.; Yang, Q.; Peng, B.; Ma, J.; Fang, Y.; Qu, L.; Li, H.; Wu, W.; Jin, L.; Sun, D. Advances in Escherichia coli Nissle 1917 as a customizable drug delivery system for disease treatment and diagnosis strategies. Mater Today Bio. 2023, 18, 100543.

 

  1. Cao, Z.; Liu, J. Bacteria and bacterial derivatives as drug carriers for cancer therapy. J Control Release. 2020, 326, 396-407.

 

  1. Zou, S.; Jie, H.; Han, X.; Wang, J. The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury. Int Immunopharmacol. 2023, 124, 110436.

 

  1. Xiong, D.; Song, L.; Chen, Y.; Jiao, X.; Pan, Z. Salmonella Enteritidis activates inflammatory storm via SPI-1 and SPI-2 to promote intracellular proliferation and bacterial virulence. Front Cell Infect Microbiol. 2023, 13, 1158888.

 

  1. Gurbatri, C. R.; Lia, I.; Vincent, R.; Coker, C.; Castro, S.; Treuting, P. M.; Hinchliffe, T. E.; Arpaia, N.; Danino, T. Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies. Sci Transl Med. 2020, 12, eaax0876.

 

  1. Liu, L.; Helal, S. E.; Peng, N. CRISPR-Cas-based engineering of probiotics. Biodes Res. 2023, 5, 0017.
Conflict of interest
The authors declare no conflicts of interest.
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