Harnessing hitchhikers: Outer membrane vesicles leading the way in advanced cancer therapeutics and diagnostic- A review.

Cancer therapy is increasingly shaped by delivery platforms designed to overcome the limitations of conventional chemotherapy and radiotherapy. Among these, bacterial outer membrane vesicles (OMVs) have emerged as versatile nanocarriers with intrinsic tumor-interacting properties, immunomodulatory capacity, and amenability to bioengineering. Their lipid bilayer composition not only enhances stability and cellular uptake but also intersects with tumor lipid metabolism-an axis increasingly recognized as central to oncogenesis, immune evasion, and therapeutic resistance. Here, we review mechanistic links between OMV lipid composition and autophagy regulation and discuss how engineered OMVs can be used to modulate tumor metabolism, immune responses, and therapy sensitivity. By influencing lipid-autophagy crosstalk, OMVs function as more than passive delivery vehicles; they can actively engage intracellular stress pathways and metabolic dependencies. Autophagy, a context-dependent regulator of cancer survival and suppression, is particularly relevant, as OMVs can deliver bioactive lipids, proteins, or nucleic acids that either promote immunogenic stress responses or attenuate tumor-protective autophagy. Preclinical examples-including doxorubicin-loaded OMVs and PD-1-engineered OMVs-illustrate how these principles translate into enhanced anti-tumor efficacy and immune activation. We further discuss how integration with lipidomics, systems biology, and artificial intelligence-guided design may improve OMV engineering and therapeutic predictability. Collectively, these advances position OMVs as a promising, though still emerging, platform for precision oncology.