Engineered microbe-based micro/nanorobots for interventional therapy of luminal cancers

Luminal cancers, including gastrointestinal, genitourinary, and peritoneal cavity-associated malignancies, are, in principle, amenable to local intervention, yet durable therapeutic control remains difficult to achieve. Although natural orifice and intracavitary routes allow direct access to the lesion, mucus barriers, luminal fluid turnover, epithelial sealing, stromal remodeling, hypoxic niches, and immunosuppressive microenvironments together restrict the penetration, retention, and sustained efficacy of conventional locoregional therapies. In this context, engineered microbe-based micro/nanorobots are emerging as a class of route-adapted living therapeutic systems for luminal cancer intervention. Unlike passive carriers, microorganisms possess intrinsic motility, niche responsiveness, interfacial adaptability, and the ability to generate bioactive outputs in situ , making them particularly suitable for local deployment followed by sustained function within cavity-associated tumors. Recent progress in synthetic biology, bacterial surface engineering, and biohybrid material integration has further enabled the conversion of native microbes into programmable systems with improved stability, lesion interaction, stimulus responsiveness, and controlled therapeutic expression. In this review, we summarize the mechanistic basis of microbe-mediated interventional therapy, including selective colonization of pathological niches, therapeutic secretion, membrane-associated activity, and immune amplification within luminal tumor microenvironments. We then discuss the major design strategies that support the transition from native microorganisms to engineered microrobotic systems, with emphasis on functional surface modification, genetic programming, and their integration. Next, we review route-specific applications across colorectal, gastric, rectal, cervical, bladder, and peritoneal malignancies through oral, suppository-based, and instillation-based interventions. Finally, we discuss key translational challenges, including safety, controllability, in vivo tracking, manufacturability, and ecological compatibility, and argue that future progress will depend on the development of clinically usable living systems that combine local deployment, barrier traversal, sustained function, and controllable clearance.