Highly Loaded Erlotinib Tubular Micromotor for Targeted Drug Delivery, pH Responsive Release and Ultrasound Tracking: A Three‐In‐One Micromachine

Herein, we report a novel erlotinib (EH) -loaded calcium carbonate (CaCO₃) tubular micromotor fabricated via an internal-filling strategy, achieving a high drug payload of 2.53 × 10^- ¹ ² mol per micromotor, which integrates three core functionalities in one system: targeted delivery of EH, pH-responsive release, and ultrasound-based tracking. The microtube structures (10 µm in diameter) are prepared by electrochemical deposition, followed by filling the EH@CaCO₃ microparticle into the interior of the tubular motor. Distinct from the surface coating approach for drug immobilization, this internal-filling strategy enables substantially greater payloads. The EH@CaCO₃ tubular micromotor shows favorable bubble and magnetic propulsion capabilities. Serving as a proof-of-concept for targeted anti-cancer drug delivery, these micromotors can transport drugs within microchips channel to the targeted position. Under acidic conditions, CaCO₃ undergoes decomposition to release the encapsulated drug. Concurrently, the Zn-based inner structure of the tubular micromotor reacts with hydrogen ions (H⁺), leading to micromotor degradation and thereby facilitating rapid drug release. The as-released drug shows cell killing ability toward non-small cell lung cancer cells A549. Meanwhile, as the micromotors move in an acidic environment, the in situ generated bubbles can act as "ultrasonic contrast agents", thereby enabling real-time tracking of the micromotors. For potential in vivo applications, this facilitates the tracking of such motors in scenarios where optical microscopy is ineffective. The blood compatibility, coagulation function, and preliminary in vivo immune response evaluation all indicate that the system had good biosafety. This study provides a new idea for the development of a next-generation micro drug delivery platform with high drug loading, intelligent delivery, and real-time visualization.