Phytochemical Engineered Bacterial Outer Membrane Vesicles for Photodynamic Effects Promoted Immunotherapy

Abstract

Cancer vaccines are emerging as an attractive modality for tumor immunotherapy. However, their practical application is seriously impeded by the complex fabrication and unsatisfactory outcomes. Herein, we construct bacterial outer membrane vesicles (OMVs)-based in situ cancer vaccine with phytochemical features for photodynamic effects-promoted immunotherapy. By simply fusing thylakoid membranes with OMVs, bacteria-plant hybrid vesicles (BPNs) are prepared. After systemic administration, BPNs can target tumor tissues and stimulate the activation of immune cells, including dendritic cells (DCs). The photodynamic effects derived from thylakoid lead to the disruption of local tumors and then the release of tumorassociated antigens that are effectively presented by DCs, inducing remarkable tumor-specific CD8 + T cell responses. Moreover, BPNs can efficiently ameliorate the immunosuppressive tumor microenvironment and further boost immune responses. Therefore, both tumor development and metastasis can be efficiently prevented. This work provides a novel idea for developing a versatile membrane-based hybrid system for highly efficient tumor treatment.

Material-Assisted Engineering of Organelles for Biomedical Applications

“…In addition to the EV derived from living mammalian cells, bacteria-derived outer membrane vesicles (OMVs) could also integrate with the NTs through lipid infusion (type 4) to form the bacteria-plant hybrid nanovesicles (BPNs; Figure 11a). 63 Through repeat coextrusion, the BPNs with a size around 226 nm could be generated with spherical morphology (Figure 11b). OMVs were prelabeled with FITC-conjugated LPS antibodies to identify the fusion, and NTs were identified by the fluorescence of chlorophyll.…”

“…Mix: OMVs and NTs treatment. Reproduced with permission from ref . Copyright 2022 American Chemical Society.…”

Bioengineered Bacterial Membrane Vesicles with Multifunctional Nanoparticles as a Versatile Platform for Cancer Immunotherapy

“…25 Nanovesicles (outer membrane vesicles, OMVs) extracted from Gram-negative bacteria such as E. coli have been demonstrated to target deep tumors through the strategy of "hitchhiking circulating neutrophils". 26,27 OMVs contain lipopolysaccharides, which are easily recognized and taken up by neutrophils. Moreover, OMVs with abundant pathogenassociated pattern molecules can trigger an immune response even in the tumor immunosuppressive condition, thereby enhancing specific immune recognition.…”

“…Nevertheless, the limited penetration ability of nanoparticles may lead to incomplete removal of deep-tissue tumors, which may result in secondary tumor recurrence and metastasis . Nanovesicles (outer membrane vesicles, OMVs) extracted from Gram-negative bacteria such as E. coli have been demonstrated to target deep tumors through the strategy of “hitchhiking circulating neutrophils”. , OMVs contain lipopolysaccharides, which are easily recognized and taken up by neutrophils. Moreover, OMVs with abundant pathogen-associated pattern molecules can trigger an immune response even in the tumor immunosuppressive condition, thereby enhancing specific immune recognition. , Photothermal therapy (PTT) is another effective strategy for tumor growth inhibition that converts light energy into heat .…”

Organism‐Generated Biological Vesicles In Situ: An Emerging Drug Delivery Strategy

“…Biological vesicles, including exosomes, [ 1 ] outer membrane vesicles (OMVs) from bacteria, [ 2 ] apoptotic bodies (ApoBDs), and microparticles, [ 3 ] are nano/micro‐scale membrane vesicles secreted by organisms, cells, or bacteria. They usually contain genetic materials and proteins from the original cells and can be used for local or systemic communications among cells.…”