Bioengineered Bacterial Outer Membrane Vesicles as Cell-Specific Drug-Delivery Vehicles for Cancer Therapy

ACS Nano ◽  
2014 ◽  
Vol 8 (2) ◽  
pp. 1525-1537 ◽  
Author(s):  
Vipul Gujrati ◽  
Sunghyun Kim ◽  
Sang-Hyun Kim ◽  
Jung Joon Min ◽  
Hyon E Choy ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Specific Drug ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Bacterial Outer Membrane

scholarly journals Bacterial Outer Membrane Vesicles as Antibiotic Delivery Vehicles

2021 ◽  
Vol 12 ◽  
Author(s):  
Shannon M. Collins ◽  
Angela C. Brown
Keyword(s):  
Outer Membrane ◽  
Cell Envelope ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Great Promise ◽  
Gram Negative ◽  
Delivery Vehicles ◽  
Bacterial Outer Membrane ◽  
Antibiotic Delivery

Bacterial outer membrane vesicles (OMVs) are nanometer-scale, spherical vehicles released by Gram-negative bacteria into their surroundings throughout growth. These OMVs have been demonstrated to play key roles in pathogenesis by delivering certain biomolecules to host cells, including toxins and other virulence factors. In addition, this biomolecular delivery function enables OMVs to facilitate intra-bacterial communication processes, such as quorum sensing and horizontal gene transfer. The unique ability of OMVs to deliver large biomolecules across the complex Gram-negative cell envelope has inspired the use of OMVs as antibiotic delivery vehicles to overcome transport limitations. In this review, we describe the advantages, applications, and biotechnological challenges of using OMVs as antibiotic delivery vehicles, studying both natural and engineered antibiotic applications of OMVs. We argue that OMVs hold great promise as antibiotic delivery vehicles, an urgently needed application to combat the growing threat of antibiotic resistance.

scholarly journals Bacterial Outer Membrane Vesicles as Nano‐Scale Bioreactors: A Fatty Acid Conversion Case Study

ChemCatChem ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4080-4086
Author(s):  
Ji‐Won Song ◽  
Yoonjin Baeg ◽  
Ha‐Yeon Jeong ◽  
Jinwon Lee ◽  
Deok‐Kun Oh ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Nano Scale ◽  
Bacterial Outer Membrane

scholarly journals Aggregatibacter actinomycetemcomitans Leukotoxin Is Delivered to Host Cells in an LFA-1-Indepdendent Manner When Associated with Outer Membrane Vesicles

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 414 ◽  
Author(s):  
Justin Nice ◽  
Nataliya Balashova ◽  
Scott Kachlany ◽  
Evan Koufos ◽  
Eric Krueger ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Aggregatibacter Actinomycetemcomitans ◽  
Aggressive Periodontitis ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Type I ◽  
Outer Membranes ◽  
Independent Mechanism ◽  
Bacterial Outer Membrane

The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans, has been associated with localized aggressive periodontitis (LAP). In particular, highly leukotoxic strains of A. actinomycetemcomitans have been more closely associated with this disease, suggesting that LtxA is a key virulence factor for A. actinomycetemcomitans. LtxA is secreted across both the inner and outer membranes via the Type I secretion system, but has also been found to be enriched within outer membrane vesicles (OMVs), derived from the bacterial outer membrane. We have characterized the association of LtxA with OMVs produced by the highly leukotoxic strain, JP2, and investigated the interaction of these OMVs with host cells to understand how LtxA is delivered to host cells in this OMV-associated form. Our results demonstrated that a significant fraction of the secreted LtxA exists in an OMV-associated form. Furthermore, we have discovered that in this OMV-associated form, the toxin is trafficked to host cells by a cholesterol- and receptor-independent mechanism in contrast to the mechanism by which free LtxA is delivered. Because OMV-associated toxin is trafficked to host cells in an entirely different manner than free toxin, this study highlights the importance of studying both free and OMV-associated forms of LtxA to understand A. actinomycetemcomitans virulence.

scholarly journals Bacterial outer membrane vesicles engineered with lipidated antigens as a platform for Staphylococcus aureus vaccine

2019 ◽  
Vol 116 (43) ◽  
pp. 21780-21788 ◽  
Author(s):  
Carmela Irene ◽  
Laura Fantappiè ◽  
Elena Caproni ◽  
Francesca Zerbini ◽  
Andrea Anesi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Vaccine Platform ◽  
Transport Pathway ◽  
Protective Antigens ◽  
Tlr4 Agonist ◽  
Engineering Strategy ◽  
Bacterial Outer Membrane

Bacterial outer membrane vesicles (OMVs) represent an interesting vaccine platform for their built-in adjuvanticity and simplicity of production process. Moreover, OMVs can be decorated with foreign antigens using different synthetic biology approaches. However, the optimal OMV engineering strategy, which should guarantee the OMV compartmentalization of most heterologous antigens in quantities high enough to elicit protective immune responses, remains to be validated. In this work we exploited the lipoprotein transport pathway to engineer OMVs with foreign proteins. Using 5 Staphylococcus aureus protective antigens expressed in Escherichia coli as fusions to a lipoprotein leader sequence, we demonstrated that all 5 antigens accumulated in the vesicular compartment at a concentration ranging from 5 to 20% of total OMV proteins, suggesting that antigen lipidation could be a universal approach for OMV manipulation. Engineered OMVs elicited high, saturating antigen-specific antibody titers when administered to mice in quantities as low as 0.2 μg/dose. Moreover, the expression of lipidated antigens in E. coli BL21(DE3)ΔompAΔmsbBΔpagP was shown to affect the lipopolysaccharide structure, with the result that the TLR4 agonist activity of OMVs was markedly reduced. These results, together with the potent protective activity of engineered OMVs observed in mice challenged with S. aureus Newman strain, makes the 5-combo-OMVs a promising vaccine candidate to be tested in clinics.

scholarly journals Optimizing Production and Purification of Bacterial Outer Membrane Vesicles

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Tyler Pugeda ◽  
Milena Dinu ◽  
Lea Michel ◽  
Timothy Chapman ◽  
Michael Pichichero
Keyword(s):  
Outer Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Bacterial Outer Membrane

scholarly journals Using Chitosan or Chitosan Derivatives in Cancer Therapy

2021 ◽  
Vol 2 (4) ◽  
pp. 795-816
Author(s):  
Md Salman Shakil ◽  
Kazi Mustafa Mahmud ◽  
Mohammad Sayem ◽  
Mahruba Sultana Niloy ◽  
Sajal Kumar Halder ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Anticancer Agents ◽  
Chitosan Nanoparticles ◽  
Chemotherapeutic Drugs ◽  
Chitosan Derivatives ◽  
Drug Delivery Vehicles ◽  
Modified Chitosan ◽  
Therapeutic Benefits ◽  
Delivery Vehicles

Cancer is one of the major causes of death worldwide. Chemotherapeutic drugs have become a popular choice as anticancer agents. Despite the therapeutic benefits of chemotherapeutic drugs, patients often experience side effects and drug resistance. Biopolymers could be used to overcome some of the limitations of chemotherapeutic drugs, as well as be used either as anticancer agents or drug delivery vehicles. Chitosan is a biocompatible polymer derived from chitin. Chitosan, chitosan derivatives, or chitosan nanoparticles have shown their promise as an anticancer agent. Additionally, functionally modified chitosan can be used to deliver nucleic acids, chemotherapeutic drugs, and anticancer agents. More importantly, chitosan-based drug delivery systems improved the efficacy, potency, cytotoxicity, or biocompatibility of these anticancer agents. In this review, we will investigate the properties of chitosan and chemically tuned chitosan derivatives, and their application in cancer therapy.

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