Micro/Nanorobot-mediated therapies for hard-to-reach lesions

Therapeutic intervention for intractable lesions located in hard-to-reach anatomical regions remains a formidable clinical challenge. These lesions are typically either insulated by robust biological barriers or sequestered within microscale tissue compartments, which severely impede the accessibility and efficacy of conventional therapeutic modalities. Despite substantial progress in nanomedicine, passive drug delivery systems still suffer from inherent limitations, including insufficient barrier penetration, non-specific in vivo biodistribution, and deficient active targeting capability, ultimately leading to compromised therapeutic efficacy and off-target side effects. Micro/nanorobots (MNRs) have revolutionized drug delivery paradigms by shifting from passive diffusion to active, locomotion-driven transportation. Powered by convertible chemical, magnetic, acoustic, or biological energy and functionalized with biomimetic camouflage strategies, MNRs are capable of autonomous navigation in complex physiological fluids, active penetration of dense biological barriers, and on-demand cargo release triggered by pathological microenvironmental cues (e.g., pH variation and reactive oxygen species accumulation). This review summarizes the latest advances in MNR-enabled therapeutic strategies for hard-to-reach lesions. We first categorize state-of-the-art MNRs based on their propulsion mechanisms. Subsequently, we elaborate on their versatile applications in barrier-shielded and micro-confined lesion therapy, with a focused discussion on core technical strategies including targeted drug delivery, MNR-mediated immunotherapy, and mitochondrial transplantation. Furthermore, we highlight the key translational bottlenecks restricting clinical implementation, covering biocompatibility and biosafety concerns, and in vivo precise motion control. We also prospect the future development directions of MNRs toward precision, minimally invasive, and personalized clinical medicine. This review aims to provide strategic insights for the rational design, performance optimization, and clinical translation of next-generation intelligent MNR therapeutic platforms.