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. Scientists are using tiny bubble-like packages from bacteria, called outer membrane vesicles (OMVs), to fight cancer. These natural carriers can deliver drugs, block tumor defenses, and help doctors track tumors, offering safer and smarter treatments. • Comprehensive discussion of OMVs as dual-purpose platforms: carriers of therapeutic molecules and regulators of intracellular processes such as autophagy. • In-depth exploration of lipid–autophagy interplay, framing OMVs as tools capable of reprogramming tumor metabolism and overcoming drug resistance. • Forward-looking perspective on integrating OMVs with artificial intelligence (AI), lipidomics, and systems biology to accelerate translation into precision oncology. • Critical comparison with other vesicular systems, positioning OMVs as versatile, tunable, and clinically promising candidates.