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WIREs Nanomed Nanobiotechnol
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Outer membrane vesicles for vaccination and targeted drug delivery

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Extracellular vesicles (EVs) are cell membrane‐derived compartments that spontaneously secrete from a wide range of cells and tissues. EVs have shown to be the carriers in delivering drugs and small interfering RNA. Among EVs, bacterial outer membrane vesicles (OMVs) recently have gained the interest in vaccine development and targeted drug delivery. In this review, we summarize the current discoveries of OMVs and their functions. In particular, we focus on the biogenesis of OMVs and their functions in bacterial virulence and pathogenesis. Furthermore, we discuss the applications of OMVs in vaccination and targeted drug delivery. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology‐Inspired Nanomaterials > Lipid‐Based Structures
Biogenesis of outer membrane vesicles (OMVs). Step 1: Gram‐negative bacteria cell envelop. In this stage, envelop proteins are homogenously distributed. Outer membrane is linked with peptidoglycan. Step 2: Vesiculation initiation. The linking between outer membrane and peptidoglycan is lost through the movement of linking proteins or breaking the connection of outer membrane with peptidoglycan directly. Models A, B, and C demonstrate three ways of OMVs production. Model A indicates the basal OMV production. Model B refers to the OMV production with enriched periplasma cargos. Model C shows the formation of OMVs that are located at specific proteins on the outer surface, and the dense proteins could induce the additional budding of OMV from Gram‐negative bacteria cell envelop
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Outer membrane vesicles (OMVs) functionality in vaccination and drug delivery. Left: (a) Natural derived OMVs vaccine formulas, including OMVs alone, OMVs combined with adjuvants, OMVs combined with bacterial antigens, and gold nanoparticles (AuNPs)‐loaded OMVs. (b) Bioengineered OMVs vaccine formula. Bacterial antigens are expressed as fusion proteins with outer membrane proteins located on the outer membrane surface of OMVs. Right: (a) Directing enzyme‐packing delivery systems for packing phosphotriesterase (PTE) enzymes in OMVs. (b) Small interfering RNA (siRNA)‐loaded bioengineered OMVs in cancer therapy
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Bioengineered bacterial outer membrane vesicles as cell‐specific drug‐delivery vehicles for cancer therapy. (a) Schematic representation of outer membrane vesicles (OMVs) expressing HER2‐specific affibody (AffiHER2OMV) and the application of AffiHER2OMV in cancer therapy. (b) Tumor‐specific retention and accumulation of delivered small interfering RNA (siRNA) in major vital organs. (c) Tumor growth inhibition (TGI) after delivery of siRNA. (Reprinted with permission from Gujrati et al. (). Copyright 2014 American Chemical Society)
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Bacterial nanobioreactors‐directing enzyme packaging into bacterial outer membrane vesicles (OMVs). (a) Crystal structures of the proteins utilized in the biorthogonal membrane conjugation of phosphotriesterase (PTE) for packaging into OMVs. (b) PTE kinetic data fit to the standard Michaelis–Menten enzyme kinetics equation for NAI and CAI UC pellet, CAI and CA UC supernatant (left), NAI and CAI represent N‐terminal‐OmpA‐SpyTag fusion construct and C‐terminal‐OmpA‐SpyTag fusion construct in presence of arabinose and ITPG (Isopropyl‐beta‐D‐1‐thiogalactopyranoside), respectively. UC represents ultracentrifugation.; a Lineweaver−Burk analysis used for determining KM and kcat/KM (right). (Reprinted with permission from Alves et al. (). Copyright 2015 American Chemical Society)
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Cryo‐transmission electron microscope visualization of outer membrane vesicles (OMVs) derived from Burkholderia pseudomallei (Nieves et al., ). Cryo‐transmission electron micrograph of purified OMVs prepared from a late logarithmic culture of B. pseuodomallei strain 1026b. Bar indicates 100 nm. (Reprinted with permission from Holst et al. (). Copyright 2010 PLoS One)
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Outer membrane vesicles (OMVs) biomodification in Acinetobacter baumannii vaccines development. Schematic diagram of the construction of recombinant Omp22‐OMVs. (Reprinted with permission from Huang et al. (). Copyright 2016 Springer Nature)
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Modulating antibacterial immunity via bacterial membrane (BM)‐coated nanoparticles. (a) Stability of extruded outer membrane vesicles (OMVs) and BM‐gold nanoparticles (AuNPs) with time. (b) BM‐AuNPs eliciting strong bacterium‐specific antibody responses in vivo. (c) BM‐AuNPs inducing pronounced bacterium‐specific T‐cell activation in vivo. (Reprinted with permission from W. Gao et al. (). Copyright 2015 American Chemical Society)
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Immunization with Escherichia coli outer membrane vesicles protects bacteria‐induced lethality via Th1 and Th17 cell responses. (a) Survival rates of outer membrane vesicle (OMV)‐ and sham‐immunized mice challenged with E. coli. (b) Survival rates of OMV‐ and sham‐immunized mice challenged with E. coli 42 d after immunization. (c) Serum levels of OMV‐reactive IgG. (d) OMV‐specific production of IFN‐g, IL‐17, IL‐4, and IL‐10 from splenic T cells. (e) Survival rates of wild‐type, IFN‐g−/−, IL‐17−/−, and IL‐4−/− mice after the E. coli injection. (Reprinted with permission from O. Y. Kim et al. (). Copyright 2013 The American Association of Immunologists, Inc)
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Biofunctions of outer membrane vesicles (OMVs). OMVs release from bacteria outer membrane layer and automatically entrap various cellular molecules. Biofunctions of OMVs are categorized and described as above, including horizontal DNA transformation, quorum sensing, toxin secretion, nutrient digestion, and misfolded protein secretion
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Biology-Inspired Nanomaterials > Lipid-Based Structures
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

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