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Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors

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Abstract

Bacterial outer membrane vesicles (OMVs) are potent immunostimulants of regulating the tumor microenvironment (TME) for immunotherapy, and can be used to deliver drugs. However, the severe systemic inflammatory response triggered by OMVs upon intravenous (i.v.) injection has limited their application. Here, we developed a safe and effective strategy by conjugating doxorubicin-loaded serum albumin (SA-DOX, AD) onto the surface of OMVs using a matrix metalloproteinase (MMP)-cleavable peptide linker (cL). This approach enabled the dynamic shielding of OMVs to reduce the systemic side effects while simultaneously enhancing the anti-tumor effects through chemo-immunotherapy. Specifically, the resulting OMV-cL-AD formulation exhibited significantly enhanced accumulation at the tumor site after i.v. administration, facilitated by the SA decoration on the OMVs surface. Subsequently, the shield on the OMV-cL-AD was cleaved by the over-expressed MMP in the TME, leading to the release of both OMVs and AD. This process provided OMV-induced immunotherapy and DOX-induced chemotherapy, resulting in synergistic tumor inhibition. In conclusion, our work demonstrated the potential of OMV-cL-AD as an effective immunochemotherapy strategy that can prolong the survival time of mice without inducing side effects.

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Acknowledgements

This work was supported by the Beijing Natural Science Foundation (No. JQ21027) and the National Natural Science Foundation of China (Nos. U2001224, 32030062, 21821005, and 82202028).

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  1. Shuping Li and Xin Li contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China

    Shuping Li & Xiao-Dong Gao

  2. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China

    Shuping Li, Xin Li, Jiaqi Meng, Weier Bao, Shuang Wang, Peng Ye, Xiao-Dong Gao & Wei Wei

  3. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, China

    Wei Wei

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  1. Shuping Li
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Correspondence to Xiao-Dong Gao or Wei Wei.

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Li, S., Li, X., Meng, J. et al. Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors. Nano Res. 17, 836–847 (2024). https://doi.org/10.1007/s12274-023-6225-6

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  • DOI: https://doi.org/10.1007/s12274-023-6225-6

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