Bacterial extracellular vesicle technology for precision cancer medicine: Biotechnological advances and applications

Bacterial extracellular vesicles (BEVs) are nanoscale secretions containing proteins, lipids, nucleic acids, and metabolites that modulate immune pathways, reshape the tumor microenvironment, and influence multiple stages of tumor progression. These properties position BEVs as promising platforms for cancer immunotherapy and precision targeted therapies. However, clinical translation is limited by low and inconsistent yields, vesicle heterogeneity, and the lack of standardized methods for isolation, characterization, and bioengineering. Compared with eukaryotic extracellular vesicles and synthetic nanocarriers, BEVs combine intrinsic immunostimulatory activity, strain-level genetic programmability, and high stability in harsh microenvironments, which may help integrate adjuvant and cargo within a single platform and support oral or mucosal delivery when derived from appropriately selected and engineered bacterial strains, while also enabling the capture of microbe-derived signals for liquid biopsy. This review adopts a technology focused perspective to synthesize recent advances in BEV based biomedical strategies for cancer. We summarize progress in elucidating vesicle biogenesis, optimizing scalable separation and purification workflows, and applying multi-omics approaches for systematic cargo profiling. Particular emphasis is placed on emerging engineering methods, including genetic modification, chemical conjugation, and strain level design, that exploit post-translational modifications to fine tune BEV stability, targeting, and immune regulatory activity. By integrating and comparing preclinical studies on probiotic derived and synthetically engineered BEVs, this review outlines how BEV platforms are being used for precise drug and nucleic acid delivery, immune modulation, and metastasis inhibition, and how their stability and molecular signatures support applications in liquid biopsy and biomarker discovery. We further discuss cross cutting bottlenecks in standardization, quality control, manufacturing, and safety assessment, and highlight engineering innovations that begin to address these challenges. Together, these insights define key research priorities for refining BEV production and functional design and provide a roadmap for advancing BEVs toward clinical grade platforms for personalized cancer therapy. These applications remain subject to biological and manufacturing constraints, which are discussed in detail in the concluding section.