Tumbling Magnetic Microrobots for Targeted In Vivo Drug Delivery in the GI Tract

Achieving reliable, on‐demand targeted drug release in dynamic environments such as the gastrointestinal tract remains a critical challenge. Here, we introduce a hollow two‐photon polymerized microrobot whose ports are sealed by a mechanically interlocked heneicosane wax cap within a suspended microgrid, retaining seal integrity during locomotion in biologically relevant environments. In vitro, microrobots loaded with doxorubicin remained stable at body temperature (37°C) and exhibited complete, step‐like discharge within 1 min once the bath temperature crossed the 40–42°C threshold. Guided by an integrated magnetic and robotic ultrasound system, microrobots were introduced rectally and navigated in vivo to the distal colon of anesthetized rats and visualized in real time. Focused ultrasound (FUS) heating to 42°C triggered on‐demand release of an echogenic nanoparticle tracer, producing a distinct contrast plume. No release occurred before reaching the targeted release temperature, underscoring the design's high thermal specificity and leakage‐free performance at body temperature. Therapeutic relevance was demonstrated in an inflammatory‐bowel‐disease cell model: doxorubicin‐filled microrobots reduced MDA‐MB‐231 viability below the projected LC50 value after 72 h. Together, the heneicosane cap and the noninvasive FUS thermal trigger enable leakage‐free storage, real‐time navigation, and spatially confined drug release in vivo, advancing untethered microrobotic delivery toward clinically actionable, colon‐targeted therapies.