Bacterial outer membrane vesicles in the fight against cancer

Bacterial outer membrane vesicles(OMVs)are diminutive vesicles naturally released by Gram-negative bacteria.These vesicles possess distinctive characteristics that attract attention for their potential use in drug administration and immunotherapy in cancer treatment.Therapeutic medicines may be delivered via OMVs directly to the tumor sites,thereby minimizing exposure to healthy cells and lowering the risk of systemic toxicity.Furthermore,the activation of the immune system by OMVs has been demonstrated to facilitate the recognition and elimination of cancer cells,which makes them a desirable tool for immunotherapy.They can also be genetically modified to carry specific antigens,immunomodulatory compounds,and small interfering RNAs,enhancing the immune response to cancerous cells and silencing genes associated with disease progression.Combining OMVs with other cancer treatments like chemotherapy and radiation has shown promising synergistic effects.This review highlights the crucial role of bacterial OMVs in cancer,emphasizing their potential as vectors for novel cancer targeted therapies.As researchers delve deeper into the complexities of these vesicles and their interactions with tumors,there is a growing sense of optimism that this avenue of study will bring positive outcomes and renewed hope to cancer patients in the foreseeable future.

Bacterial outer membrane vesicles-based therapeutic platform eradicates triple-negative breast tumor by combinational photodynamic/chemo-/immunotherapy

Bacterial outer membrane vesicles(OMVs)are potent immuno-stimulating agents and have the potentials to be bioengineered as platforms for antitumor nanomedicine.In this study,OMVs are demonstrated as promising antitumor therapeutics.OMVs can lead to beneficial M2-to-M1 polarization of macrophages and induce pyroptosis to enhance antitumor immunity,but the therapeutic window of OMVs is narrow for its toxicity.We propose a bioengineering strategy to enhance the tumor-targeting ability of OMVs by macrophage-mediated delivery and improve the antitumor efficacy by co-loading of photosensitizer chlorin e6(Ce6)and chemotherapeutic drug doxorubicin(DOX)into OMVs as a therapeutic platform.We demonstrate that systemic injection of the DOX/Ce6-OMVs@M therapeutic platform,providing combinational photodynamic/chemo-/immunotherapy,eradicates triple-negative breast tumors in mice without side effects.Importantly,this strategy also effectively prevents tumor metastasis to the lung.This OMVs-based strategy with bioengineering may serve as a powerful therapeutic platform for a synergic antitumor therapy.

30 and 32 kDa outer membrane proteins of Bordetella pertussis as a modulator on promoting degranulation of mast cells

The correlation between the activities of the outer menbrane proteins （OMPs） of Bordetella pertussis and the lgE-mediated asthma was investigated in the present study, in which the OMPs of B. pertussis and their components were prepared by detergent treatment and chromatography, and the molecular weights of the OMPs components were determined by SDS-PAGE. The amounts of total as well as the ovalbumin （OVA）-specific IgE induced by dead B. pertussis whole bacterial vaccine on guinea pigs were detected by ELISA. Meanwhile, the effect of the OMPs and their components to promote the degranulation of guinea pig mast cells was observed by using the mast cell degranulation test, and ELISA assay was used to measure the histatmine levels in the supematants from the mast cell cultures. Histamine sensitive test was used to demonstrate the effects of the OMPs and their components to increase the histamine lethal sensitivity in mice. It was found that four components with molecular weights of 30, 32, 38 and 69 kDa could be obtained from the OMPs of B. pertussts, and the dead whole bacteria vaccine of B. pertussis had the ability to increase the levels of the total as well as the OVA-specific IgE in sera of guinea pigs. The OMPs and their 30 and 32 kDa components demonstrated significantly enhancing effect on the degranulation of guinea pig mast cells, and the histamine levels in the supematants from the mast cell culture treated with OMPs and their 30 and 32 kDa components were also significantly increased. It is evident that the strong adjuvant activity and the enhancing effect to degranulation of mast cells and the release of histamine of certain outer membrane components of B. pertussis could be demonstrated as revealed by the results of the present study, suggesting the possibility of a close relationship between the infection of vaccination with B. pertussis and the IgE-mediated asthma.

A smart DNA hydrogel for isolation of bacterial outer membrane vesicles and localized cancer immunotherapy

Bacterial outer membrane vesicles(OMVs)have shown great potential in cancer immunotherapy.The isolation of OMVs from complex media with high purity and high bioactivity is the prerequisite of therapeutic applications,which remains highly challenging.Herein,we report a smart DNA hydrogel for the efficient isolation of OMVs from bacterial culture medium,which is further applied for localized cancer immunotherapy.The DNA hydrogel is constructed through the cross-linking of two ultralong DNA chains generated via rolling circle amplification(RCA).One chain contains polyvalent GN6 aptamer for the specific capture of OMVs,and the other contains polyvalent programmed death-1(PD-1)aptamer for the blocking of PD-1 immune checkpoint on the surface of T lymphocytes.The OMVs capsulated by DNA hydrogel maintain high immunostimulatory bioactivity.In the mouse model of melanoma,this OMVs-containing DNA hydrogel shows a remarkable tumor inhibition rate of∼95%.This smart DNA hydrogel represents a promising biomedical platform for the efficient isolation of bacterial-derived OMVs,and provides a powerful strategy for cancer immunotherapy.