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Nano Research 2024, 17(2): 836-847 https://doi.org/10.1007/s12274-023-6225-6
Research Article | Issue | Published: 17 November 2023

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

Show Author's Information Shuping Li1,2,§,  Xin Li2,§,  Jiaqi Meng2,  Weier Bao2,  Shuang Wang2,  Peng Ye2,  Xiao-Dong Gao1,2( ),  Wei Wei2,3( )
Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China

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

Keywords:
immunotherapy, chemotherapy, doxorubicin, tumor microenvironment, outer membrane vesicles
Topics:
Chemotherapy Nanobiotechnology
Cite this article:
Li S, Li X, Meng J, et al. Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors. Nano Research, 2024, 17(2): 836-847. https://doi.org/10.1007/s12274-023-6225-6
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Abstract Full text Electronic supplementary material About this article

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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Abstract
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Electronic supplementary material
About this article

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

Show Author's information Shuping Li1,2,§, Xin Li2,§, Jiaqi Meng2, Weier Bao2, Shuang Wang2, Peng Ye2, Xiao-Dong Gao1,2( ), Wei Wei2,3( )
Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China

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

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.

Keywords: immunotherapy, chemotherapy, doxorubicin, tumor microenvironment, outer membrane vesicles

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Publication history
Copyright
Acknowledgements

Publication history

Received: 04 August 2023
Revised: 20 September 2023
Accepted: 20 September 2023
Published: 17 November 2023
Issue date: February 2024

Copyright

© Tsinghua University Press 2023

Acknowledgements

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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