Autonomous Microrobots for Spatiotemporally Active Therapeutic Delivery and Controlled Release

The clinical efficacy of many conventional passive drug delivery systems is frequently constrained by their low targeting efficiency, important off-target toxicity, and inadequate capacity for traversing biological barriers. Autonomous microrobots, as miniature intelligent platforms capable of active navigation and on-demand responsiveness, offer an active delivery strategy for achieving spatiotemporally precise targeted therapy. This review aims to systematically consolidate and critique the theoretical foundations, key technologies, cutting-edge applications, and future challenges of this emergent interdisciplinary field. We first provide an in-depth analysis of the technological frameworks underpinning the 2 core functionalities: targeted delivery and on-demand release. This encompasses a diverse array of propulsion and navigation strategies—from chemical and physical fields to biohybrid systems—as well as programmed drug release mechanisms responsive to endogenous and exogenous stimuli. Building on this, we introduce a hierarchical paradigm organized by biological-barrier traversal capability to review the preclinical progress of microrobots, from localized delivery in accessible body cavities to deep-tissue and trans-barrier applications. This function-oriented framework more directly links microrobot design to the progressive physiological constraints encountered in vivo, thereby providing a more integrated and translationally relevant perspective on biomedical applications and clinical potential. Concurrently, this paper examines the bottlenecks impeding their clinical translation, including biosafety, systemic controllability, and regulatory science. Looking forward, the deep integration of microrobotics with smart materials, artificial intelligence, and theranostic systems is poised to cultivate a new generation of intelligent medical robots capable of personalized treatment via closed-loop manners.