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Theranostics 2024; 14(2):761-787. doi:10.7150/thno.85917 This issue Cite

Review

Engineered bacterial outer membrane vesicles: a versatile bacteria-based weapon against gastrointestinal tumors

Keshuang Zheng^1,2,3*, Yongpu Feng^1,2,3*, Lei Li^4*, Fanyang Kong^1,2,3✉, Jie Gao^5✉, Xiangyu Kong^1,2,3,5✉

1. National Key Laboratory of Immunology and Inflammation, Naval Medical University, Shanghai, 200433, China.
2. Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of the Ministry of Education and the Collaborative Innovation Center for Brain Science, Naval Medical University, Shanghai, 200433, China.
3. Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China.
4. Digestive Endoscopy Center, Shanghai Tenth People's Hospital, Shanghai, China.
5. Changhai Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
* Co-first authors.

✉ Corresponding authors: Xiangyu Kong, Jie Gao and Fanyang Kong, Email: xiangyukong185com, gaojiehighcleacom, and kfy8195288com.

Abstract

Outer membrane vesicles (OMVs) are nanoscale lipid bilayer structures released by gram-negative bacteria. They share membrane composition and properties with their originating cells, making them adept at traversing cellular barriers. These OMVs have demonstrated exceptional membrane stability, immunogenicity, safety, penetration, and tumor-targeting properties, which have been leveraged in developing vaccines and drug delivery systems. Recent research efforts have focused on engineering OMVs to increase production yield, reduce cytotoxicity, and improve the safety and efficacy of treatment. Notably, gastrointestinal (GI) tumors have proven resistant to several traditional oncological treatment strategies, including chemotherapy, radiotherapy, and targeted therapy. Although immune checkpoint inhibitors have demonstrated efficacy in some patients, their usage as monotherapy remains limited by tumor heterogeneity and individual variability. The immunogenic and modifiable nature of OMVs makes them an ideal design platform for the individualized treatment of GI tumors. OMV-based therapy enables combination therapy and optimization of anti-tumor effects. This review comprehensively summarizes recent advances in OMV engineering for GI tumor therapy and discusses the challenges in the clinical translation of emerging OMV-based anti-tumor therapies.

Keywords: outer membrane vesicles, gastrointestinal tumors, genetic engineering, cargo delivery, tumor vaccine

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