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Tuning Bacterial Morphology to Enhance Anticancer Vaccination

  • Chu-Xin Li
    Chu-Xin Li
    Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China
    More by Chu-Xin Li
  • , 
  • Yongdan Qi
    Yongdan Qi
    Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China
    More by Yongdan Qi
  • , 
  • Yingge Chen
    Yingge Chen
    Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China
    More by Yingge Chen
  • , 
  • Yu Zhang
    Yu Zhang
    Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China
    More by Yu Zhang
  • , 
  • Bin Li
    Bin Li
    School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, PR China
    More by Bin Li
    Orcidhttps://orcid.org/0000-0002-4417-8383
  • , 
  • Jun Feng*
    Jun Feng
    Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China
    *Email: [email protected]
    More by Jun Feng
    Orcidhttps://orcid.org/0000-0002-1725-140X
  • , and 
  • Xian-Zheng Zhang
    Xian-Zheng Zhang
    Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China
    More by Xian-Zheng Zhang
    Orcidhttps://orcid.org/0000-0001-6242-6005
Cite this: ACS Nano 2023, 17, 9, 8815–8828
Publication Date (Web):April 24, 2023
https://doi.org/10.1021/acsnano.3c02373
Copyright © 2023 American Chemical Society
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    Abstract

    Abstract Image

    Morphology tuning is a potent strategy to modulate physiological effects of synthetic biomaterials, but it is rarely explored in microbe-based biochemicals due to the lack of artificial adjustability. Inspired by the interesting phenomenon of microbial transformation, Escherichia coli is rationally adjusted into filamentous morphology-adjusted bacteria (MABac) via chemical stimulation to prepare a bacteria-based vaccine adjuvant/carrier. Inactivated MABac display stronger immunogenicity and special delivery patterns (phagosome escape and cytoplasmic retention) that are sharply distinct from the short rod-shaped bacteria parent (Bac). Transcriptomic study further offers solid evidence for deeply understanding the in vivo activity of MABac-based vaccine, which more effectively motivates multiple cytosolic immune pathways (such as NOD-like receptors and STING) and induces pleiotropic immune responses in comparison with Bac. Harnessing the special functions caused by morphology tuning, the MABac-based adjuvant/carrier significantly improves the immunogenicity and delivery profile of cancer antigens in vivo, thus boosting cancer-specific immunity against the melanoma challenge. This study validates the feasibility of tuning bacterial morphology to improve their biological effects, establishing a facile engineering strategy that upgrades bacterial properties and functions without complex procedures like gene editing.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.3c02373.

    • Supplemental figures (19), including the SEM images for bacteria observation, cell viability data, representative flow cytometry plots, average radiant efficiency data, gene-set enrichment analysis data, survival rate of mice, profiles of intratumoral CD4-positive T cells, and tumor volume/body weight growth data (PDF)

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