Janus micro/nanomotors for enhanced disease treatment through their deep penetration capability

Nanotherapeutic systems have provided an innovative means for the treatment of a wide range of diseases in modern medicine. However, the limited penetration of nanoparticles into focal tissues still greatly hampered their clinical application. With their unique two-sided structure and superior motility, Janus micro/nanomotors are expected to significantly improve the penetration of nanocarriers into organisms, thereby enhancing the therapeutic effects of diseases. This review introduces Janus micro/nanomotors with different morphologies and focuses on their propulsion mechanisms, including chemical field-driven, external physical field-driven, biologically-driven, and hybrid-driven mechanisms. We explore the research progress of Janus micro/nanomotors in various disease treatment areas (including cancer, cardiovascular diseases, neurological diseases, bacterial/fungal infections, and chronic inflammatory diseases) and elucidate the implementation strategies of Janus micro/nanomotors in facilitating disease therapies. Finally, we discuss the biosafety and biocompatibility of Janus micro/nanomotor, while exploring current challenges and opportunities in the field. We look forward to the Janus micro/nanomotor therapeutic platform demonstrating surprising therapeutic effects in the clinical treatment of diseases. STATEMENT OF SIGNIFICANCE: Micro/nanomotors are the highly promising nanotherapeutic systems due to their self-propelled motion capability. Janus micro/nanomotors possess an asymmetric structure with different physical or chemical properties on both sides. The flexibility of this bifunctional surface allows them to hold promise for improving the penetration of nanotherapeutic systems and enhancing therapeutic efficacy for complex diseases. This review focuses on the latest advancements in Janus micro/nanomotors for enhanced disease treatment, including the structural types and driving mechanisms, the enhancement effect to cope with different disease treatments, the biocompatibility and safety, the current challenges and possible solutions. These insights inform the design of deep-penetrating nanotherapeutic systems and the strategies of enhanced disease treatment.