Engineering nanoplatforms of bacterial outer membrane vesicles to overcome cancer therapy resistance

Abstract

Resistance to cancer therapy is driven by physical barriers, tumor heterogeneity, selective therapeutic pressure, immunosuppressive tumor microenvironment (TME) and others. Bacterial outer membrane vesicles (OMVs) represent a promising nanotherapeutic platform to combat cancer therapy resistance. This review discusses the dual roles of OMVs in tumorigenesis and cancer therapy, highlighting their potential applications to enhance treatment efficacy. OMVs from pathogenic bacteria, such as Fusobacterium nucleatum and Helicobacter pylori, exacerbate chemoresistance by reshaping TME through hypoxia-induced metabolic reprogramming and immune evasion, while OMVs from some bacteria, such as probiotics, counteract immunosuppression by promoting cytotoxic T-cell infiltration and macrophage polarization. As bio-derived and conveniently engineered drug delivery platforms, OMVs maximize the synergetic anticancer effect by pathogen associated molecular patterns and the payloads. These functional payloads include siRNAs, cytotoxicity and molecular agents, and immune checkpoint inhibitors. Bacterial OMVs demonstrate unique advantages through their capacity to penetrate physical barriers, achieve tumor-specific targeting, activate immune responses, to overcome cancer therapy resistance. A successful example is the OMV-based nanoplatform with engineered OMVs co-delivering CD47-siRNA and doxorubicin to overcome drug resistance by inducing immunogenic cell death and dendritic cell activation of glioblastoma. Furthermore, OMV-based cancer vaccines presented with tumor antigens or hybridized with tumor-derived membranes enhance dendritic cell maturation and antigen-specific T-cell responses, reversing treatment resistance. By addressing challenges in mass production and safety concerns, OMVs-based platforms can be developed as powerful tools for more effective and personalized cancer treatments.