Miniature soft robots have evolved into various therapeutic materials because of their good adaptability. Nonetheless, complex terrains inside the body, especially soft wrinkled topographies with non-Newtonian viscous mucus in the gastrointestinal (GI) tract, pose a strict demand for the navigation of such robots. To address this challenge, a design inspired by sea urchins is proposed to fabricate a soft-cone-assisted rolling robot (SCARBot) by encapsulating blood coagulation gel, creating a hollow cylindrical structure for loading drugs inside. The arrangement of an array of soft cones with manually designed hydrophobicity allows for controlled locomotion of the robots under a low-frequency magnetic field, significantly reducing surface friction and improving environmental adaptability. This motion ability is further supported by ultrasound (US) imaging-guided navigation in the ex vivo and even in vivo GI tract. When a high-frequency magnetic field is applied, the drug-loaded blood coagulation gel inside the robot melts by a magnetothermal effect, thereby releasing drugs at the targeted location. The synergy of magnetothermal and pharmacological therapy enables this robot to exhibit enhanced antibacterial efficiency for ex vivo and in vivo bacterial infection and inflammation. Soft robots with exceptional adaptability and therapeutic functions offer high potential for targeted delivery and therapy through lumens inside the body.

In recent years, miniature robots have shown remarkable potential for applications in the fields of in vivo drug delivery, disease treatment, and extreme environment sensing. However, due to their high structural rigidity, poor biocompatibility, low adaptability in complex terrains, and lack of active obstacle avoidance, traditional synthetic miniature robots can usually only be investigated for proof-of-concept studies while ignoring their in vivo safety or the complexity of the application environments, which is still a significant gap from the needs of practical applications in vivo or in extreme environments. Due to their superior biocompatibility and living biological function, living biohybrid miniature robots (LBMs) have great clinical applications in vivo disease diagnosis and treatment, and in extreme environment sensing, search, and rescue. They have environmental adaptive capabilities comparable to natural organisms, thus maximizing the functionality and locomotor capabilities of living organisms. Here, we systematically summarize the components and fabrication strategies of LBMs, and comprehensively discuss the driving modes of them, as well as the efficient goal-oriented realization of these mechanisms in specific application scenarios. Finally, we discuss the current challenges facing the field and provide an outlook on future developments and research directions.

Untethered and self-transformable miniature robots are capable of performing reconfigurable deformation and on-demand locomotion, which aid the traversal toward various lumens, and bring revolutionary changes for targeted delivery in gastrointestinal (GI) tract. However, the viscous non-Newtonian liquid environment and plicae gastricae obstacles severely hamper high-precision actuation and payload delivery. Here, we developed a low-friction soft robot by assembly of densely arranged cone structures and grafting of hydrophobic monolayers. The magnetic orientation encoded robot can move in multiple modes, with a substantially reduced drag, terrain adaptability, and improved motion velocity across the non-Newtonian liquids. Notably, the robot stiffness can be reversibly controlled with magnetically induced hardening, enabling on-site scratching and destruction of antibiotic-ineradicable polymeric matrix in biofilms with a low-frequency magnetic field. Furthermore, the magnetocaloric effect can be utilized to eradicate the bacteria by magnetocaloric effect under high-frequency alternating field. To verify the potential applications inside the body, the clinical imaging-guided actuation platforms were developed for vision-based control and delivery of the robots. The developed low-friction robots and clinical imaging-guided actuation platforms show their high potential to perform bacterial infection therapy in various lumens inside the body.